Comprehensive Physiology Wiley Online Library

Gene Expression and Protein Degradation

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Transcription
1.1 RNA Synthesis
1.2 mRNA Levels
1.3 Transcriptional and Posttranscriptional Processing of mRNA
1.4 Factors That Regulate Transcription
1.5 Effect of Dietary Restriction on Transcription
2 Translation
2.1 Protein Synthesis
2.2 Effect of Dietary Restriction on Protein Synthesis
2.3 Fidelity of Protein Synthesis
2.4 Various Steps of Protein Synthesis
3 Protein Degradation
3.1 Degradation of Mixed Protein Populations
3.2 Degradation of Individual Proteins
3.3 Degradation of Abnormal Proteins
3.4 Effect of Dietary Restriction on Protein Degradation
4 Summary and Conclusions
Figure 1. Figure 1.

Effect of age on RNA synthesis by rat liver. The graph on the left shows the rate of RNA synthesis by nuclei isolated from the livers of rats of various ages, and the graph on the right shows the rate of total RNA synthesis (•) and poly(A)+ RNA synthesis (○) by hepatocytes isolated from rats of various ages.

data taken from Castle et al. data taken from Richardson et al. ]
Figure 2. Figure 2.

Effect of donor age on RNA synthesis in human fibroblasts. Fibroblasts were obtained from the foreskin of normal white males of various ages and RNA synthesis measured as the incorporation of radioactive UTP into RNA.

data taken from Chen et al. and figure taken from Richardson et al. , with permission
Figure 3. Figure 3.

Effect of age on the degradation of hsp70 mRNA. Levels of hsp70 transcript were measured in hepatocytes isolated from 6‐ (□) and 26‐ (▪) month‐old rats after a brief heat shock.

data taken from Heydari et al.
Figure 4. Figure 4.

Effect of age on the expression of albumin. Synthesis (▪) and mRNA levels (□) of albumin were measured in the livers of rats of various ages.

data taken from Horbach et al.
Figure 5. Figure 5.

Effect of age on the expression of α2u‐globulin. Synthesis (•), mRNA levels (○), and nuclear transcription (○) of α2u‐globulin were measured in hepatocytes isolated from rats of various ages.

data taken from Richardson et al.
Figure 6. Figure 6.

Effect of age on the expression of genes by spleen lymphocytes. The biological activity (□) and mRNA levels (▪) of interleukin 2 (IL2), IL3, and granulocyte/macrophage colony‐stimulating factor (GMCSF) in mitogen‐stimulated lymphocytes isolated from the spleen of mice of various ages is shown.

data taken from Li et al. and Cai et al.
Figure 7. Figure 7.

Effect of age on the induction of tyrosine hydroxylase expression in the adrenal gland. The enzyme activity and the level of the mRNA transcript for tyrosine hydroxylase were determined in the adrenal gland of rats of various ages before (shaded bars) and after (solid bars) treatment with reserpine.

data taken from Strong et al.
Figure 8. Figure 8.

Effect of age on the expression of Gsα and c‐myc. The left graph shows the levels of Gsα protein, mRNA, and nuclear transcription by the renal cortex of 6‐(shaded bars) and 24‐ (solid bars) month‐old rats. The graph on the right shows the levels of the mRNA transcript and the nuclear transcription of c‐myc in lymphocytes isolated from young and old human subjects before (shaded bars) and after (solid bars) mitogen stimulation.

data taken from Hanai et al. and Liang et al. data taken from Gamble et al.
Figure 9. Figure 9.

Effect of age on DNA methylation. The percentage of 5mC in DNA isolated from the mucosa of the small intestine of Mus musculus (▪) and Peromyscus leucopus (□) of various ages is shown.

data taken from Wilson et al.
Figure 10. Figure 10.

Effect of age on the induction of c‐fos and c‐jun in rat heart. The levels of the mRNA transcripts for c‐fos and c‐jun were measured in the hearts of 9‐ and 18‐month‐old rats 90 (▪) and 180 (▪) minutes after acute pressure overload or in sham (▪)‐operated rats.

data taken from Takahashi et al.
Figure 11. Figure 11.

Effect of dietary restriction on the expression of α2u — globulin. The synthesis, mRNA levels, and nuclear transcription of α2a — globulin by hepatocytes isolated from 18–month‐old rats fed ad libitum (shaded bars) and a calorie‐restricted diet (solid bars) are shown.

data taken from Richardson et al.
Figure 12. Figure 12.

Effect of age on protein synthesis by invertebrates. Cell‐free incorporation of [3H]‐leucine into protein by microsomes from D. melanogaster [○, data taken from Webster ] and the in vivo incorporation of [3H]‐leucine into protein by nematodes [•, data taken from Sharma et al. ] are shown.

Figure taken from Richardson and Birchenall‐Sparks with permission
Figure 13. Figure 13.

Effect of age on protein synthesis by various tissues of rats. The left graph shows the relative protein synthetic activity of liver [○, data taken from Coniglio et al. ], brain [Δ, data taken from Ekstrom et al. ], kidney [•, data taken from Hardwick et al. ], testes [▴, data taken from Liu et al. ], and mitogen‐stimulated spleen lymphocytes [, data taken from Cheung et al. ] of Fischer 344 rats. The right graph shows the relative protein synthetic activity of liver [, data taken from Bolla and Greenblatt ], pancreas [•, data taken from Kim et al. ], parotid gland [○, data taken from Kim et al. ], heart mitochondria [Δ, data taken from Starnes et al. ], and testes [▴, data taken from Richardson and Myers ] of Sprague‐Dawley rats.

Figure taken from Richardson and Birchenall‐Sparks with permission
Figure 14. Figure 14.

Variation in the age‐related decline in the synthesis of individual proteins by rat liver. A comparison of the decrease in the rate of synthesis of 35 proteins between 5 and 30 months of age is shown for rat hepatocytes.

data taken from Butler et al.
Figure 15. Figure 15.

Effect of dietary restriction on protein synthesis by rat liver. The rate of protein synthesis by hepatocytes isolated from rats fed ad libitum (□) or a calorie‐restricted diet (▪) is shown.

data were taken from Birchenall‐Sparks et al.
Figure 16. Figure 16.

Effect of age on ribosome aggregation to mRNA. The sedimentation of polyribosomes in sucrose gradients is shown for skeletal muscle], liver], and brain of rats.

data taken from Pluskal et al. data taken from Layman et al. data taken from Fando et al.
Figure 17. Figure 17.

Effect of age on the elongation of protein synthesis in rat liver. The ribosomal half‐transit times for hepatocytes isolated from 4‐month‐old (A) and 18–month‐old (B) rats are shown.

Figure taken rom Coniglio et al. with permission
Figure 18. Figure 18.

Effect of age on the activity of EF‐1α. The activity of EF‐1α is shown for D. melanogaster

A, data taken from Webster and Webster ], nematodes [B, data taken from Bolla and Brot ], and rat liver [C, data taken from Moldave et al.
Figure 19. Figure 19.

Pathway of protein degradation in mammalian cells.

Figure 20. Figure 20.

Effect of age on protein degradation in rat liver. The rate of protein degradation by perfused liver from rats fed ad libitum (○) or a calorie‐restricted diet (•) is shown as a function of age.

data taken from Ward with permission
Figure 21. Figure 21.

Effect of age on the accumulation of oxidized proteins in rat liver. Left: levels of carbonyl groups in soluble proteins in the livers of rats of various ages is shown [data taken from Starke‐Reed and Oliver ]. Right: levels of carbonyl groups in the frontal pole (FP) and occipital pole (OP) of brain obtained from 16 patients at autopsy.

data taken from Smith et al. with permission
Figure 22. Figure 22.

Effect of age on the degradation of abnormal peptides by rat liver. After rats received an injection of [3H]‐puromycin, they were given unlabeled puromycin (•) or saline (▪). The radioactivity in puromycinyl peptides in the liver of 6‐month‐old (a) and 24–25‐month‐old (b) rats is shown.

Figure taken from Lavie et al. with permission
Figure 23. Figure 23.

Effect of age on the degradation of oxidized proteins. A: comparison of levels of carbonyl groups in soluble protein in livers of rats of various ages to activity of alkaline protease activity [taken from Starke‐Reed and Oliver with permission]. B: carbonyl content of protein, glutamine synthetase activity, and alkaline protease activity of brains from old (15–18 months) gerbils compared to brains of young (3 months) gerbils as 100%.

data taken from Carney et al. with permission


Figure 1.

Effect of age on RNA synthesis by rat liver. The graph on the left shows the rate of RNA synthesis by nuclei isolated from the livers of rats of various ages, and the graph on the right shows the rate of total RNA synthesis (•) and poly(A)+ RNA synthesis (○) by hepatocytes isolated from rats of various ages.

data taken from Castle et al. data taken from Richardson et al. ]


Figure 2.

Effect of donor age on RNA synthesis in human fibroblasts. Fibroblasts were obtained from the foreskin of normal white males of various ages and RNA synthesis measured as the incorporation of radioactive UTP into RNA.

data taken from Chen et al. and figure taken from Richardson et al. , with permission


Figure 3.

Effect of age on the degradation of hsp70 mRNA. Levels of hsp70 transcript were measured in hepatocytes isolated from 6‐ (□) and 26‐ (▪) month‐old rats after a brief heat shock.

data taken from Heydari et al.


Figure 4.

Effect of age on the expression of albumin. Synthesis (▪) and mRNA levels (□) of albumin were measured in the livers of rats of various ages.

data taken from Horbach et al.


Figure 5.

Effect of age on the expression of α2u‐globulin. Synthesis (•), mRNA levels (○), and nuclear transcription (○) of α2u‐globulin were measured in hepatocytes isolated from rats of various ages.

data taken from Richardson et al.


Figure 6.

Effect of age on the expression of genes by spleen lymphocytes. The biological activity (□) and mRNA levels (▪) of interleukin 2 (IL2), IL3, and granulocyte/macrophage colony‐stimulating factor (GMCSF) in mitogen‐stimulated lymphocytes isolated from the spleen of mice of various ages is shown.

data taken from Li et al. and Cai et al.


Figure 7.

Effect of age on the induction of tyrosine hydroxylase expression in the adrenal gland. The enzyme activity and the level of the mRNA transcript for tyrosine hydroxylase were determined in the adrenal gland of rats of various ages before (shaded bars) and after (solid bars) treatment with reserpine.

data taken from Strong et al.


Figure 8.

Effect of age on the expression of Gsα and c‐myc. The left graph shows the levels of Gsα protein, mRNA, and nuclear transcription by the renal cortex of 6‐(shaded bars) and 24‐ (solid bars) month‐old rats. The graph on the right shows the levels of the mRNA transcript and the nuclear transcription of c‐myc in lymphocytes isolated from young and old human subjects before (shaded bars) and after (solid bars) mitogen stimulation.

data taken from Hanai et al. and Liang et al. data taken from Gamble et al.


Figure 9.

Effect of age on DNA methylation. The percentage of 5mC in DNA isolated from the mucosa of the small intestine of Mus musculus (▪) and Peromyscus leucopus (□) of various ages is shown.

data taken from Wilson et al.


Figure 10.

Effect of age on the induction of c‐fos and c‐jun in rat heart. The levels of the mRNA transcripts for c‐fos and c‐jun were measured in the hearts of 9‐ and 18‐month‐old rats 90 (▪) and 180 (▪) minutes after acute pressure overload or in sham (▪)‐operated rats.

data taken from Takahashi et al.


Figure 11.

Effect of dietary restriction on the expression of α2u — globulin. The synthesis, mRNA levels, and nuclear transcription of α2a — globulin by hepatocytes isolated from 18–month‐old rats fed ad libitum (shaded bars) and a calorie‐restricted diet (solid bars) are shown.

data taken from Richardson et al.


Figure 12.

Effect of age on protein synthesis by invertebrates. Cell‐free incorporation of [3H]‐leucine into protein by microsomes from D. melanogaster [○, data taken from Webster ] and the in vivo incorporation of [3H]‐leucine into protein by nematodes [•, data taken from Sharma et al. ] are shown.

Figure taken from Richardson and Birchenall‐Sparks with permission


Figure 13.

Effect of age on protein synthesis by various tissues of rats. The left graph shows the relative protein synthetic activity of liver [○, data taken from Coniglio et al. ], brain [Δ, data taken from Ekstrom et al. ], kidney [•, data taken from Hardwick et al. ], testes [▴, data taken from Liu et al. ], and mitogen‐stimulated spleen lymphocytes [, data taken from Cheung et al. ] of Fischer 344 rats. The right graph shows the relative protein synthetic activity of liver [, data taken from Bolla and Greenblatt ], pancreas [•, data taken from Kim et al. ], parotid gland [○, data taken from Kim et al. ], heart mitochondria [Δ, data taken from Starnes et al. ], and testes [▴, data taken from Richardson and Myers ] of Sprague‐Dawley rats.

Figure taken from Richardson and Birchenall‐Sparks with permission


Figure 14.

Variation in the age‐related decline in the synthesis of individual proteins by rat liver. A comparison of the decrease in the rate of synthesis of 35 proteins between 5 and 30 months of age is shown for rat hepatocytes.

data taken from Butler et al.


Figure 15.

Effect of dietary restriction on protein synthesis by rat liver. The rate of protein synthesis by hepatocytes isolated from rats fed ad libitum (□) or a calorie‐restricted diet (▪) is shown.

data were taken from Birchenall‐Sparks et al.


Figure 16.

Effect of age on ribosome aggregation to mRNA. The sedimentation of polyribosomes in sucrose gradients is shown for skeletal muscle], liver], and brain of rats.

data taken from Pluskal et al. data taken from Layman et al. data taken from Fando et al.


Figure 17.

Effect of age on the elongation of protein synthesis in rat liver. The ribosomal half‐transit times for hepatocytes isolated from 4‐month‐old (A) and 18–month‐old (B) rats are shown.

Figure taken rom Coniglio et al. with permission


Figure 18.

Effect of age on the activity of EF‐1α. The activity of EF‐1α is shown for D. melanogaster

A, data taken from Webster and Webster ], nematodes [B, data taken from Bolla and Brot ], and rat liver [C, data taken from Moldave et al.


Figure 19.

Pathway of protein degradation in mammalian cells.



Figure 20.

Effect of age on protein degradation in rat liver. The rate of protein degradation by perfused liver from rats fed ad libitum (○) or a calorie‐restricted diet (•) is shown as a function of age.

data taken from Ward with permission


Figure 21.

Effect of age on the accumulation of oxidized proteins in rat liver. Left: levels of carbonyl groups in soluble proteins in the livers of rats of various ages is shown [data taken from Starke‐Reed and Oliver ]. Right: levels of carbonyl groups in the frontal pole (FP) and occipital pole (OP) of brain obtained from 16 patients at autopsy.

data taken from Smith et al. with permission


Figure 22.

Effect of age on the degradation of abnormal peptides by rat liver. After rats received an injection of [3H]‐puromycin, they were given unlabeled puromycin (•) or saline (▪). The radioactivity in puromycinyl peptides in the liver of 6‐month‐old (a) and 24–25‐month‐old (b) rats is shown.

Figure taken from Lavie et al. with permission


Figure 23.

Effect of age on the degradation of oxidized proteins. A: comparison of levels of carbonyl groups in soluble protein in livers of rats of various ages to activity of alkaline protease activity [taken from Starke‐Reed and Oliver with permission]. B: carbonyl content of protein, glutamine synthetase activity, and alkaline protease activity of brains from old (15–18 months) gerbils compared to brains of young (3 months) gerbils as 100%.

data taken from Carney et al. with permission
References
 1. Ammendola, R., M. Mesuraca, T. Russo, and F. Cimino. Sp1 DNA binding efficiency is highly reduced in nuclear extracts from aged rat tissues. J. Biol. Chem. 267: 17944–17948, 1992.
 2. Ann, D. K., H. H. Lin, S. Lee, Z. Tu, and E. Wang. Characterization of the statin‐like S1 and rat elongation factor 1 a as two distinctly expressed messages in rat. J. Biol. Chem. 267: 699–702, 1992.
 3. Ann, D. K., I. K. Moutsatsos, T. Nakamura, H. H. Lin, P. Mao, M. Lee, S. Chin, R. K. Liem, and E. Wang. Isolation and characterization of the rat chromosomal gene for a polypeptide (pS1) antigenically related to statin. J. Biol. Chem. 266: 10429–10437, 1991.
 4. Armbrecht, H. J., M. Boltz, R. Strong, A. Richardson, M. E. H. Burns, and S. Christakos. Expression of calbindin‐D decreases with age in intestine and kidney. Endocrinology 125: 2950–2956, 1989.
 5. Avola, R., D. F. Condorelli, N. Ragusa, M. Renis, M. Alberghina, A. M. Giuffrida Stella, and A. Lajtha. Protein synthesis rates in rat brain regions and subcellular fractions during aging. Neurochem. Res. 13: 337–342, 1988.
 6. Azelis, A. E., K. M. McMullen, and G. C. Webster. Progressive reduction in protein synthesis during involution and aging of the mouse thymus. Mech. Ageing Dev. 20: 361–368, 1982.
 7. Bacci, B., L. Petrelli, R. Dal Toso, and M. G. Nunzi. Age‐associated alteration in the expression of synapsin I mRNA in the rat central nervous system. Ann. N.Y. Acad. Sci. 663: 463–465, 1992.
 8. Bailey, P. J., and G. C. Webster. Lowered rates of protein synthesis by mitochondria isolated from organisms of increasing age. Mech. Ageing Dev. 24: 233–241, 1984.
 9. Baker, G. T., and T. Schmidt. Changes in 80S ribosomes from Drosophila melanogaster with age. Experientia 32: 1505–1506, 1976.
 10. Barrows, C. H., and G. C. Kokkonen. The effect of age and diet on the cellular protein synthesis of liver of male mice. Age 10: 54–57, 1987.
 11. Barrows, C. H., and L. M. Roeder. Effect of age on protein synthesis in rats. J. Gerontol. 16: 321–325, 1961.
 12. Baum, B. J., B. L. Kuyatt, and S. Humphreys. Protein production and processing in young adult and aged rat submandibular gland cells in vitro. Mech. Ageing Dev. 23: 123–136, 1983.
 13. Baumann, P., and P. S. Chen. Alterung and proteinsynthese bei Drosophila melanogaster. Rev. Suisse Zool. 69: 1051–1055, 1969.
 14. Beauchene, R. E., L. M. Roeder, and C. H. Barrows. The effect of age and ethionine feeding on RNA and protein synthesis of rats. J. Gerontol. 22: 318–324, 1967.
 15. Beauchene, R. E., L. M. Roeder, and C. H. Barrows, Jr.. The interrelationships of age, tissue protein synthesis, and proteinuria. J. Gerontol. 25: 359–363, 1970.
 16. Benson, R. W., and C. W. Harker. RNA polymerase activities in liver and brain tissue of aging mice. J. Gerontol. 33: 323–328, 1978.
 17. Berkowitz, E. M., A. C. Sanborn, and D. W. Vaughan. Chromatin structure in neuronal and neuroglial cell nuclei as a function of age. J. Neurochem. 41: 516–523, 1983.
 18. Bernd, A., E. Batke, P. K. Zahn, and W. E. Muller. Age‐dependent gene induction in quail oviduct. XV. Alterations of the poly (A)‐associated protein pattern and of the poly(A) chain length of mRNA. Mech. Ageing Dev. 19: 361–377, 1982.
 19. Besse, S., P. Assayag, C. Delcayre, F. Carre, S.‐L. Cheav, Y. Lecarpentier, and B. Swynghedauw. Normal and hypertrophied senescent rat heart: mechanical and molecular characteristics. Am. J. Physiol. 265 (Heart Circ. Physiol. 36): H183–H190, 1993.
 20. Biggs, R. B., and F. W. Booth. Protein synthesis rate is not suppressed in rat heart during senescence. Am. J. Physiol. 258 (Heart Circ. Physiol. 29): H207–H211, 1990.
 21. Biggs, R. B., R. M. Hanley, P. R. Morrison, and F. W. Booth. Cytochrome c mRNA levels decrease in senescent rat heart. Mech. Ageing Dev. 60: 285–293, 1991.
 22. Birchenall‐Sparks, M. C., M. S. Roberts, M. S. Rutherford, and A. Richardson. The effect of aging on the structure and function of liver messenger RNA. Mech. Ageing Dev. 32: 99–111, 1985.
 23. Birchenall‐Sparks, M. C., M. S. Roberts, J. Staecker, J. P. Hardwick, and A. Richardson. Effect of dietary restriction on liver protein synthesis in rats. J. Nutr. 115: 944–950, 1985.
 24. Blake, M. J., J. Fargnoli, D. Gershon, and N. J. Holbrook. Concomitant decline in heat‐induced hyperthermia and HSP70 and mRNA expression in aged rats. Am. J. Physiol. 260: 663–667, 1991.
 25. Blake, M. J., R. Udelsman, G. J. Feulner, D. D. Norton, and N. J. Holbrook. Stress‐induced heat shock protein 70 expression in adrenal cortex: an adrenocorticotropic hormone‐sensitive, age‐dependent response. Proc. Natl. Acad. Sci. U.S.A. 88: 9873–9877, 1991.
 26. Blazejowski, C. A., and G. C. Webster. Decreased rates of protein synthesis by cell‐free preparations from different organs of aging mice. Mech. Ageing Dev. 21: 345–356, 1983.
 27. Blazejowski, C. A., and G. C. Webster. Effect of age on peptide chain initiation and elongation in preparations from brain, liver, kidney and skeletal muscle of the C57B/6J mouse. Mech. Ageing Dev. 25: 323–333, 1984.
 28. Bloom, E. T., H. Umehara, R. C. Bleackley, K. Okumura, H. Mostowski, and J. T. Babbitt. Age‐related decrement in cytotoxic T lymphocyte (CTL) activity is associated with decreased levels of mRNA encoded by two CTL‐associated serine esterase genes and the perforin gene in mice. Eur. J. Immunol. 20: 2309–2316, 1990.
 29. Bolla, R., and N. Brot. Age dependent changes in enzymes involved in macromolecular synthesis in turbatrix aceti. Arch. Biochem. Biophys. 169: 227–236, 1975.
 30. Bolla, R., and W. D. Denckla. Effect of hypophysectomy on liver ribonucleic acid synthesis in aging rats. Biochem. J. 184: 669–674, 1979.
 31. Bolla, R., and J. Miller. Endogenous nucleotide pools and protein incorporation into liver nuclei from young and old rats. Mech. Ageing Dev. 12: 107–118, 1980.
 32. Bolla, R. I., and C. Greenblatt. Age‐related changes in rat liver total protein and tranferrin synthesis. Age 5: 72–79, 1982.
 33. Britton, G. W., and F. G. Sherman. Altered regulation of protein synthesis during aging as determined by in vitro ribosomal assays. Exp. Gerontol. 10: 67–77, 1975.
 34. Britton, V. J., F. G. Sherman, and J. R. Florini. Effect of age on RNA synthesis by nuclei and soluble RNA polymerases from liver and muscle of C57BL/6J mice. J. Gerontol. 27: 188–192, 1972.
 35. Buckler, A. J., H. Vie, G. E. Sonenshein, and R. A. Miller. Defective T lymphocytes in old mice: diminished production of mature c‐myc RNA after mitogen exposure not attributable to alterations in transcription or RNA stability. J. Immunol. 140: 2442–2446, 1988.
 36. Buetow, D. E., and P. S. Gandhi. Decreased protein synthesis by microsomes isolated from senescent rat liver. Exp. Gerontol. 8: 243–249, 1973.
 37. Bunnemann, B., R. Metzger, K. Fuxe, and D. Ganten. Regional expression of angiotensinogen mRNA in the brain of one‐week‐old, adult and old male rats. Dev. Brain Res. 73: 41–45, 1993.
 38. Burrows, R. B., and P. F. Davison. Protein catabolism in cultures of hepatocytes derived from mice of various ages. Mech. Ageing Dev. 19: 85–94, 1982.
 39. Butler, J. A., A. R. Heydari, and A. Richardson. Analysis of effect of age on synthesis of specific proteins by hepatocytes. J. Cell. Physiol. 141: 400–409, 1989.
 40. Buttrick, P., A. Malhotra, S. Factor, D. Geenen, L. Leinwand, and J. Scheuer. Effect of aging and hypertension on myosin biochemistry and gene expression in the rat heart. Circ. Res. 68: 645–652, 1991.
 41. Butzow, J. J., M. G. McCool, and G. L. Eichhorn. Does the capacity of ribosomes to control translation fidelity change with age. Mech. Ageing Dev. 15: 203–216, 1981.
 42. Cai, N. S., D. D. Li, H. T. Cheung, and A. Richardson. The expression of granulocyte/macrophage colony‐stimulating factor in activated mouse lymphocytes declines with age. Cell. Immunol. 130: 311–319, 1990.
 43. Carney, J. M., P. E. Starke‐Reed, C. N. Oliver, R. W. Landum, M. S. Cheng, J. F. Wu, and R. A. Floyd. Reversal of age‐related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin‐trapping compound N‐tert‐butyl‐α‐phenylnitrone. Proc. Natl. Acad. Sci. U.S.A. 88: 3633–3636, 1991.
 44. Carrier, L., K. R. Boheler, C. Chassagne, D. de la Bastie, C. Wisnewsky, E. G. Lakatta, and K. Schwartz. Expression of the sarcomeric actin isogenes in the rat heart with development and senescence. Circ. Res. 70: 999–1005, 1992.
 45. Carter, K. C., D. J. Post, and J. Papaconstantinou. Differential expression of the mouse α1‐acid glycoprotein genes (AGP‐1 and AGP‐2) during inflammation and aging. Biochim. Biophys. Acta. 1089: 197–205, 1991.
 46. Castle, T., A. Katz, and A. Richardson. Comparison of RNA synthesis by liver nuclei from rats of various ages. Mech. Ageing Dev. 8: 383–395, 1978.
 47. Cavallius, J., S. I. Rattan, and B. F. Clark. Changes in activity and amount of active elongation factor la in aging and immortal human fibroblast cultures. Exp. Gerontol. 21: 149–157, 1986.
 48. Cavallius, J., S. I. Rattan, B. Riis, and B. F. Clark. A decrease in levels of mRNA for elongation factor‐1α accompanies the decline in its activity and the amounts of active enzyme in rat livers during ageing. In: The Liver, Metabolism and Ageing, edited by K. W. Woodhouse, C. Yelland, and O. F. W. James. Rijswijk, Netherlands: INSERM‐EURAGE/Libbey 1989, p. 125–132.
 49. Cedar, H. DNA methylation and gene activity. Cell 53: 3–4, 1988.
 50. Chang, W. C., M. T. Hoopes, and G. S. Roth. Biosynthetic rates of protein having the characteristics of glucocorticoid receptors in adipocytes of mature and senescent rats. J. Gerontol. 36: 386–390, 1981.
 51. Chatterjee, B., G. Fernandes, B. P. Yu, C. Song, J. M. Kim, W. Demyan, and A. K. Roy. Calorie restriction delays age‐dependent loss in androgen responsiveness of the rat liver. FASEB J. 3: 169–173, 1989.
 52. Chatterjee, B., S. T. Nath, and A. K. Roy. Differential regulation of the messenger RNA for three major senescence maker proteins in male rat liver. J. Biol. Chem. 256: 5939–5941, 1981.
 53. Chaturvedi, M. M., and M. S. Kanungo. Analysis of conformation and function of the chromatin of the brain of young and old rats. Mol. Biol. Rep. 10: 215–219, 1985.
 54. Chen, J. C., P. Ove, and A. I. Lansing. In vitro synthesis of microsomal protein and albumin in young and old rats. Biochim. Biophys. Acta 312: 598–607, 1973.
 55. Chen, J. J., N. Brot, and H. Weissbach. RNA and protein synthesis in cultured human fibroblasts derived from donors of various ages. Mech. Ageing Dev. 13: 285–295, 1980.
 56. Chen, P. S., Amino acid pattern and rate of protein synthesis in aging drosophila. In: Molecular Genetic Mechanisms in Development and Aging, edited by M. Rockstein and G. T. Bakker. New York: Academic Press, 1972, p. 199–226.
 57. Cheung, H. T., J. S. Twu, and A. Richardson. Mechanism of the age‐related decline in lymphocyte proliferation: role of IL‐2 production and protein synthesis. Exp. Gerontol. 18: 451–460, 1983.
 58. Claes‐Reckinger, N., J. Vandenhaute, C. F. van Bezooijen, and J. Delcour. Functional properties of rat liver protein synthesizing machinery in relation to aging. Exp. Gerontol. 17: 281–286, 1982.
 59. Clarke, J. M., and J. M. Smith. Increase in the rate of protein synthesis with age in Drosophila subobscura. Nature 209: 627–629, 1966.
 60. Clinton, M., M. Frangou‐Lazaridis, C. Panneerselvam, and B. L. Horecker. Prothymosin α and parathymosin: mRNA and polypeptide levels in rodent tissues. Arch. Biochem. Biophys. 269: 256–263, 1989.
 61. Coleman, P. K., B. B. Kaplan, H. H. Oosterburg, and C. E. Finch. Brain poly (A) RNA during aging: stability of yield and sequence complexity in two rat strains. J. Neurochem. 34: 335–345, 1980.
 62. Collins, J. M. RNA synthesis in rat liver cells with different DNA contents. J. Biol. Chem. 253: 5769–5773, 1978.
 63. Comolli, R. Polyamine effects of carbon‐14 leucine transfer to microsomal protein in a rat liver cell free system during aging. Exp. Gerontol. 8: 307–313, 1973.
 64. Comolli, R., M. E. Ferioli, and S. Azzola. Protein turnover of the lysosomal and mitochondrial fractions of rat liver during aging. Exp. Gerontol. 7: 369–376, 1972.
 65. Coniglio, J. J., D. S. Liu, and A. Richardson. A comparison of protein synthesis by liver parenchymal cells isolated from Fischer F344 rats of various ages. Mech. Ageing Dev. 11: 77–90, 1979.
 66. Cook, J. R., and D. E. Buetow. The complement of cytoplasmic tRNAs, including queuosine‐containing tRNAs, in adult and senescent Wistar rat liver and their levels of aminoacylation. Mech. Ageing Dev. 20: 289–304, 1982.
 67. Cosgrove, J. W., and S. I. Rapoport. Absence of age differences in protein synthesis by rat brain, measured with an initiating cell‐free system. Neurobiol. Aging 8: 27–34, 1987.
 68. Courtright, J. B., J. Sonstein, and A. K. Kumaran. Age specific regulation of gene expression in Drosophila. In: Molecular Biology of Aging: Gene Stability and Gene Expression, edited by R. S. Sohal, L. S. Birnbaum, and R. G. Cutler. New York: Raven Press, 1985, p. 209–222.
 69. Crew, M. D., S. R. Spindler, R. L. Walford, and A. Koizumi. Age‐related decrease of growth hormone and prolactin gene expression in the mouse pituitary. Endocrinology 121: 1251–1255, 1987.
 70. Crie, J. S., D. J. Millward, P. C. Bates, E. E. Griffin, and K. wlldenthal. Age‐related alterations in cardiac protein turnover. J. Mol. Cell. Cardiol. 13: 589–598, 1981.
 71. Cutler, R. G., The dysdifferentiative hypothesis of mammalian aging and longevity. In: The Aging Brain, edited by E. Giacobini, G. Giacobini, G. Filogamo, and A. Vernadakis. New York: Raven Press, 1982, p. 25–114.
 72. Danner, D. B., and N. J. Holbrook. Alterations in gene expression with aging. In: Handbook of the Biology of Aging, edited by E. L. Schneider and J. W. Rowe. San Diego: Academic Press, 1990, p. 97–115.
 73. D'Costa, A., C. R. Breese, R. L. Boyd, R. M. Booze, and W. E. Sonntag. Attenuation of fos‐like immunoreactivity induced by a single electroconvulsive shock in brains of aging mice. Brain Res. 567: 204–211, 1991.
 74. Demyan, W. F., C. S. Song, D. S. Kim, S. Her, W. Gallwitz, T. R. Rao, M. Slomczynska, B. Chatterjee, and A. K. Roy. Estrogen sulfotransferase of the rat liver: complementary DNA cloning and age‐ and sex‐specific regulation of messenger RNA. Mol. Endocrinol. 6: 589–597, 1992.
 75. Denckla, W. D. System analysis of possible mechanisms of mammalian aging. Mech. Ageing Dev. 6: 143–152, 1977.
 76. Devi, A., P. Lindsay, P. L. Raina, and N. K. Sarkar. Effect of age on some aspects of the synthesis of ribonucleic acid. Nature 212: 474–475, 1966.
 77. De Vries, A. C., M. A. Vermeer, A. L. Hendriks, H. Bloemendal, and L. H. Cohen. Biosynthetic capacity of the human lens upon aging. Exp. Eye Res. 53: 519–524, 1991.
 78. Dice, J. F. Altered degradation of proteins microinjected into senescent human fibroblasts. J. Biol. Chem. 257: 14624–14627, 1982.
 79. Dice, J. F., and H. Chiang. Peptide signals for protein degradation within lysosomes. Biochem. Soc. Symp. 55: 45–55, 1989.
 80. Dobie, D. J., M. A. Miller, M. A. Raskind, and D. M. Dorsa. Testosterone reverses a senescent decline in extrahypothalamic vasopressin mRNA. Brain Res. 583: 247–252, 1992.
 81. Drinkwater, R. D., T. J. Blake, A. A. Morley, and D. R. Turner. Human lymphocytes aged in vivo have reduced levels of methylation in transcriptionally active and inactive DNA. Mutat. Res. 219: 29–37, 1989.
 82. Du, J. T., T. A. Beyer, and C. A. Lang. Protein biosynthesis in aging mouse tissues. Exp. Gerontol. 12: 181–191, 1977.
 83. Dubitsky, R., K. G. Bensch, and J. E. Fleming. Age‐related changes on turnover and concentration of a subset of thorax polypeptides from Drosophila melanogaster. Mech. Ageing Dev. 32: 311–317, 1985.
 84. Dwyer, B. E., J. L. Fando, and C. G. Wasterlain. Rat brain protein synthesis declines during postdevelopmental aging. J. Neurochem. 35: 746–749, 1980.
 85. Egilmez, N. K., and M. Rothstein. The effect of aging on cell‐free protein synthesis in the free‐living nematode Turbatrix aceti. Biochim. Biophys. Acta 840: 355–363, 1985.
 86. Ekstrom, R., D. S. Liu, and A. Richardson. Changes in brain protein synthesis during the life span of male Fischer rats. Gerontology 26: 121–128, 1980.
 87. El Haj, A. J., S. E. Lewis, D. F. Goldspink, B. J. Merry, and A. M. Holehan. The effect of chronic and acute dietary restriction on the growth and protein turnover of fast and slow types of rat skeletal muscle. Comp. Biochem. Physiol. A 85: 281–287, 1986.
 88. Fairweather, D. S., M. Fox, and G. P. Margison. The in vitro lifespan of MRC‐5 cells in shortened by 5‐azacytidine‐induced demethylation. Exp. Cell Res. 168: 153–159, 1987.
 89. Fando, J. L., M. Salinas, and C. G. Wasterlain. Age‐dependent changes in brain protein synthesis in the rat. Neurochem. Res. 5: 373–383, 1980.
 90. Fargnoli, J., T. Kunisada, A. J. Fornace, E. L. Schneider, and N. J. Holbrook. Decreased expression of heat shock protein 70 mRNA and protein after heat treatment in cells of aged rats. Proc. Natl. Acad. Sci. U.S.A. 87: 846–850, 1990.
 91. Ferland, G., M. Audet, and B. Tuchweber. Effect of dietary restriction on lysosomal bodies and total protein synthesis in hepatocytes of aging rats. Mech. Ageing Dev. 64: 49–59, 1992.
 92. Fernandez‐Silva, P., V. Petruzzella, F. Fracasso, M. N. Gadaleta, and P. Cantore. Reduced synthesis of mtRNA in isolated mitochondria of senescent rat brain. Biochem. Biophys. Res. Commun. 176: 645–653, 1991.
 93. Filion, A. M., and M. Laughrea. Translation fidelity in the aging mammal: studies with an accurate in vitro system on aged rats. Mech. Ageing Dev. 29: 125–142, 1985.
 94. Finch, C. E., and D. G. Morgan. RNA and protein metabolism in the aging brain. Annu. Rev. Neurosci. 13: 75–87, 1990.
 95. Fleming, J. E., P. S. Melnikoff, G. I. Latter, D. Chandra, and K. G. Bensch. Age dependent changes in the expression of drosophila mitochondrial proteins. Mech. Ageing Dev. 34: 63–72, 1986.
 96. Fleming, J. E., E. Quattrocki, G. Latter, J. Miquel, R. Marcuson, E. Zuckerkandl, and K. G. Bensch. Age‐dependent changes in proteins of Drosophila melanogaster. Science 231: 1157–1159, 1986.
 97. Fletcher, M. J., and D. R. Sanadi. Turnover of liver mitochondrial components in adult and senescent rats. J. Gerontol. 16: 255–257, 1961.
 98. Florine, D. L., T. Ono, R. G. Cutler, and M. J. Getz. Regulation of endogenous murine leukemia virus‐related nuclear and cytoplasmic RNA complexity in C57BL/6J mice of increasing age. Cancer Res. 40: 519–523, 1980.
 99. Florini, J. R., S. Geary, Y. Saito, E. J. Manowitz, and R. S. Sorrentino. Changes in protein synthesis in heart. Adv. Exp. Med. Biol. 61: 149–162, 1975.
 100. Florio, T., C. Ventra, A. Postiglione, and G. Schettini. Age‐related alterations of somatostatin gene expression in different rat brain areas. Brain Res. 557: 64–68, 1991.
 101. Fog, R., and H. Pakkenberg. Age‐related changes in 3H‐uridine uptake in the mouse. J. Gerontol. 36: 680–681, 1981.
 102. Foote, R. S., and M. P. Stulberg. Efficiency and fidelity of cell‐free protein synthesis by transfer RNA from aged mice. Mech. Ageing Dev. 13: 93–104, 1980.
 103. Frazer, J. M., and W. K. Yang. Isoaccepting transfer ribonucleic acid in liver and brain of young and old BC3F1 mice. Arch. Biochem. Biophys. 153: 610–618, 1972.
 104. Fujita, T., and N. Maruyama. Elevated levels of c‐jun and c‐fos transcripts in the aged rat liver. Biochem. Biophys. Res. Commun. 178: 1485–1491, 1991.
 105. Fukuda, H., and N. Iritani. Effects of aging on gene expression of acetyl‐CoA carboxylase and fatty acid synthase in rat liver. J. Biochem. 122: 277–280, 1992.
 106. Gaardsvoll, H., L. Krog, D. Zhernosekov, A.‐M. Andersson, K. Edvardsen, M. Olsen, E. Bock, and D. Linnemann. Age‐related changes in expression of neural cell adhesion molecule (NCAM) in heart: a comparative study of newborn, adult and aged rats. Eur. J. Cell Biol. 61: 100–107, 1993.
 107. Gabius, H. J., R. Engelhardt, F. Deerberg, and F. Cramer. Age‐related changes in different steps of protein synthesis of liver and kidney of rats. FEBS Lett. 160: 115–118, 1983.
 108. Gadaleta, M. N., V. Petruzzella, M. Renis, F. Fracasso, and P. Cantatore. Reduced transcription of mitochondrial DNA in the senescent rat; tissue dependence and effect of l‐carnitine. Eur. J. Biochem. 187: 501–506, 1990.
 109. Gamble, D. A., R. Schwab, M. E. Weksler, and P. Szabo. Decreased steady state c‐myc mRNA in activated T cell cultures from old humans is caused by a smaller proportion of T cells that transcribe the c‐myc gene. J. Immunol. 144: 3569–3573, 1990.
 110. Gaubatz, J., M. Ellis, and R. Chalkley. The structural organization of mouse chromatin as a function of age. FASEB J. 38: 1973–1978, 1979.
 111. Gaubatz, J., M. Ellis, and R. Chalkley. Nuclease digestion studies of mouse chromatin as a function of age. J. Gerontol. 34: 672–679, 1979b.
 112. Gaubatz, J. W., and R. G. Cutler. Mouse satellite DNA is transcribed in senescent cardiac muscle. J. Biol. Chem. 265: 17753–17758, 1990.
 113. Gaubatz, J. W., B. Arcement, and R. G. Cutler. Gene expression of an endogenous retrovirus‐like element during murine development and aging. Mech. Ageing Dev. 57: 71–85, 1991.
 114. Geary, S., and J. R. Florini. Effect of age on rate of protein synthesis in isolated perfused mouse hearts. J. Gerontol. 27: 325–332, 1972.
 115. Gibas, M. A., and D. Harman. Ribonucleic acid synthesis by nuclei isolated from rats of different ages. J. Gerontol. 25: 105–107, 1970.
 116. Goldspink, D. F. Pre‐ and post‐natal growth and protein turnover in the lung of the rat. Biochem. J. 242: 275–279, 1987.
 117. Goldspink, D. F. Protein turnover and growth of the rat brain from the foetus to old age. J. Neurochem. 50: 1364–1368, 1988.
 118. Goldspink, D. F., and F. J. Kelly. Protein turnover and growth in the whole body, liver and kidney of the rat from the fetus to senility. Biochem. J. 217: 507–516, 1984.
 119. Goldspink, D. F., and B. J. Merry. Changes in protein turnover and growth of the rat lung in response to ageing and long‐term dietary restriction. Mech. Ageing Dev. 42: 253–262, 1988.
 120. Goldspink, D. F., S. E. Lewis, and F. J. Kelly. Protein synthesis during the developmental growth of the small and large intestine of the rat. Biochem, J. 217: 527–534, 1984.
 121. Goldspink, D. F., S. E. Lewis, and F. J. Kelly. Protein turnover and cathepsin B activity in several tissues of foetal and senescent rats. Comp. Biochem. Physiol. 82B: 849–853, 1985.
 122. Goldspink, D. F., S. E. Lewis, and B. J. Merry. Effects of aging and long term dietary intervention on protein turnover and growth of ventricular muscle in the rat heart. Cardiovasc. Res. 20: 672–678, 1986.
 123. Goldspink, D. F., A. J. el Haj, S. E. Lewis, B. J. Merry, and A. M. Holehan. The influence of chronic dietary intervention on protein turnover and growth of the diaphragm and extensor digitorum longus muscles of the rat. Exp. Gerontol. 22: 67–78, 1987.
 124. Goldstein, S., D. Stotland, and R. A. J. Cordeiro. Decreased proteolysis and increased amino acid efflux in aging human fibroblasts. Mech. Ageing Dev. 5: 221–223, 1976.
 125. Gordon, S. M., and C. E. Finch. An electrophoretic study of protein synthesis in brain regions of senescent male mice. Exp. Gerontol. 9: 267–273, 1974.
 126. Gozes, I., B. L. Cronin, and M. A. Moskowitz. Protein synthesis in rat brain microvessels decreases with aging. J. Neurochem. 36: 1311–1315, 1981.
 127. Gresik, E. W., K. Wenk‐Salamone, A. Onetti‐Muda, R. M. Gubits, and P. A. Shaw. Effect of advanced age on the induction by androgen or thyroid hormone of epidermal growth factor and epidermal growth factor mRNA in the submandibular glands of C57BL/6 male mice. Mech. Ageing Dev. 34: 175–189, 1986.
 128. Gurley, R., and J. F. Dice. Degradation of endocytosed proteins is unaltered in senescent human fibroblasts. Cell Biol. Int. Rep. 12: 885–894, 1988.
 129. Haining, J. L., and W. W. Correll. Turnover of tryptophan‐induced tryptophan pyrrolase in rat liver as a function of age. J. Gerontol. 24: 143–148, 1969.
 130. Haining, J. L., and J. S. Legan. Catalase turnover in rat liver and kidney as a function of age. Exp. Gerontol. 8: 85–91, 1973.
 131. Haji, M., R. S. Chuknyiska, and G. S. Roth. Isolated uterine nuclei and cytosol receptors of aged rats exhibit impaired estrogenic stimulation of RNA polymerase II. Proc. Natl. Acad. Sci. U.S.A. 81: 7481–7484, 1984.
 132. Hanai, H., C. T. Liang, L. Cheng, and B. Sacktor. Densensitization to parathyroid hormone in renal cells from aged rats is associated with alterations in G‐protein activity. J. Clin. Invest. 83: 268–277, 1989.
 133. Hardwick, J., W. H. Hsieh, D. S. Liu, and A. Richardson. Cell‐free protein synthesis by kidney from the aging female Fischer F344 rat. Biochim. Biophys. Acta. 652: 204–217, 1981.
 134. Hellthaler, V. G., D. Reigegerste, R. Kohler, and W. Rotzsch. Zur molekularbiologie des alterns 7 mitteilung: Einflub der cytosolfraktion auf die aminosaureinkorporation durch rattenlebermikrosomen in abhangigkeit vom lebensalter. Z. Alfernsforseh 31: 457–460, 1976.
 135. Hershko, A., and A. Ciechanover. Mechanisms of intracellular protein breakdown. Annu. Rev. Biochem. 51: 335–364, 1982.
 136. Heslop, J. P. Effect of age on [14C] valine turnover into locust wing proteins [Abstract]. Biochem. J. 104: 5P–6P, 1967.
 137. Heydari, A. R., and A. Richardson. Does gene expression play any role in the mechanism of the antiaging effect of dietary restriction. Ann. N.Y. Acad. Sci. 663: 384–395, 1992.
 138. Heydari, A. R., B. Wu, R. Takahashi, R. Strong, and A. Richardson. Expression of heat shock protein 70 is altered by age and diet at the level of transcription. Mol. Cell. Biol. 13: 2909–2918, 1993.
 139. Higgins, G. A., G. A. Oyler, R. L. Neve, K. S. Chen, and F. H. Gage. Altered levels of amyloid protein precursor transcripts in the basal forebrain of behaviorally impaired aged rats. Proc. Natl. Acad. Sci. U.S.A. 87: 3032–3036, 1990.
 140. Higuchi, K., K. Kitagawa, K. Kogishi, and T. Takeda. Developmental and age‐related changes in apolipoprotein B mRNA editing in mice. J. Lipid Res. 33: 1753–1764, 1992.
 141. Hill, B. T., and R. D. H. Whelan. Studies of the degradation of ageing chromatin DNA by nuclear and cytoplasmic factors and deoxyribonucleases. Gerontology 24: 326–336, 1978.
 142. Hill, M. W., and J. Karthigasan. Glucose metabolism and protein synthesis in stratified squamous epithelia from young and old mice. Exp. Gerontol. 24: 331–340, 1989.
 143. Holbrook, N. J., R. K. Chopra, M. T. McCoy, J. E. Nagel, D. C. Powers, W. H. Adler, and E. L. Schneider. Expression of interleukin 2 and the interleukin 2 receptor in aging rats. Cell. Immunol. 120: 1–9, 1989.
 144. Holliday, R. Strong effects of 5–azacytidine on the in vitro lifespan of human diploid fibroblasts. Exp. Cell Res. 166: 543–552, 1986.
 145. Horbach, G. J., H. M. G. Princen, M. Van der Kroef, C. F. van Bezooijen, and S. H. Yap. Changes in the sequence content of albumin mRNA and in its translational activity in the rat liver with age. Biochim. Biophys. Acta 783: 60–66, 1984.
 146. Horbach, G. J., J. G. Van Asten, and C. F. van Bezooijen. The influence of ageing on the induction of the mRNAs of rat liver cytochromes P450IIB1 and P450IIB2. Biochem. Pharmacol. 40: 529–533, 1990a.
 147. Horbach, G. J., J. G. Van Asten, and C. F. van Bezooijen. The influence of age on the inducibility of rat liver cytochrome P450IA (CYPIA1) and P450IA2 (CYPIA2) mRNAs. Mutat. Res. 237: 117–121, 1990b.
 148. Horbach, G. J., C. F. van Bezooijen, and D. L. Knook. Age‐related changes in the synthesis of individual liver‐specific proteins. In: Review of Biological Research in Aging, edited by M. Rothstein. New York: Alan R. Liss, 1987, vol. 3, p. 485–494.
 149. Horbach, G. J., H. van der Boom, C. F. van Bezooijen, S. H. Yap. Molecular aspects of age‐related changes in albumin synthesis in female WAG/Rij rats. Life Sci. 43: 1707–1714, 1988.
 150. Horbach, G. J., J. T. Venkatraman, and G. Fernandes. Food restriction prevents the loss of isosafrole inducible cytochrome P‐450 mRNA and enzyme levels in aging rats. Biochem. Int. 20: 725–730, 1990.
 151. Hosbach, H. A., and E. Kubli. Transfer RNA in aging Drosophila: I. Extent of aminoacylation. Mech. Ageing Dev. 10: 131–140, 1979a.
 152. Hosbach, H. A., and E. Kubli. Transfer RNA in aging Drosophila: II. Isoacceptor patterns. Mech. Ageing Dev. 10: 141–149, 1979b.
 153. Hrachovec, J. P. Age changes in amino acid incorporations by rat liver microsomes. Gerontologia 15: 52–63, 1969.
 154. Hrachovec, J. P. The effect of age on tissue protein synthesis. I. Age changes in amino acid incorporation by rat liver purified microsomes. Gerontologia 17: 75–86, 1971.
 155. Hung, L., and A. Richardson. The effect of aging on the genetic expression of renin by mouse kidney. Aging Clin. Exp. Res. 5: 193–198, 1993.
 156. Ibrahim, N. G., K. L. Marcus, and M. L. Freedman. Maintenance of cytochrome P450 content in old rat livers in spite of decreased mitochondrial protein synthesis. J. Clin. Exp. Gerontol. 3: 327–337, 1981.
 157. Ingvar, M. C., P. Maeder, L. Sokoloff, and C. B. Smith. Effects of ageing on local rates of cerebral protein synthesis in Sprague‐Dawley rats. Brain 108: 155–170, 1985.
 158. Ishigami, A., and S. Goto. Inactivation kinetics of horseradish peroxidase microinjected into hepatocytes of mice of various ages. Mech. Ageing Dev. 46: 125–133, 1988.
 159. Ishigami, A., and S. Goto. Age‐related change in the degradation rate of ovalbumin microinjected into mouse liver parenchymal cells. Arch. Biochem. Biophys. 277: 189–195, 1990a.
 160. Ishigami, A., and S. Goto. Effect of dietary restriction on the degradation of proteins in senescent mouse liver parenchymal cells in culture. Arch. Biochem. Biophys. 238: 362–366, 1990b.
 161. Jacobus, S., and D. Gershon. Age‐related changes in inducible mouse liver enzymes: ornithine decarboxylase and tyrosine amino‐transferase. Mech. Ageing Dev. 12: 311–322, 1980.
 162. Jaiswal, Y. K., and M. S. Kanungo. Expression of actin and myosin heavy chain genes in skeletal, cardiac and uterine muscles of young and old rats. Biochem. Biophys. Res. Commun. 168: 71–77, 1990.
 163. Johnson, T. E., and G. McCaffrey. Programmed aging or error catastrophe? An ecanination by two dimensional polyacrylamide gel electrophoresis. Mech. Ageing Dev. 30: 285–297, 1985.
 164. Junghahn, I., and H. Bielka. Regulation der translation in eukaryotischen zellen. II. Uber die altersabhangige wirkung des zytosols der leber auf die in vitro proteinsynthese in einem polysomensystem. Acta Biol. Med. Germ. 32: 267–269, 1974.
 165. Kaminska, B., and L. Kaczmarek. Robust induction of AP‐1 transcription factor DNA binding activity in the hippocampus of aged rats. Neurosci. Lett. 153: 189–191, 1993.
 166. Kanungo, M. S., O. Koul, and K. R. Reddy. Concomitant studies on RNA and protein syntheses in tissues of rats of various ages. Exp. Gerontol. 5: 261–269, 1970.
 167. Karelus, K., and J. F. Nelson. Aging impairs estrogenic suppression of hypothalamic proopiomelanocortin messenger ribonucleic acid in the mouse. Neuroendocrinology 55: 627–633, 1992.
 168. Karey, K. P., and M. Rothstein. Evidence for the lack of lysosomal involvement in the age‐related slowing of protein breakdown in Turbatrix aceti. Mech. Ageing Dev. 35: 169–178, 1986.
 169. Kelly, F. J., S. E. Lewis, R. G. Anderson, and D. F. Goldspink. Pre‐ and postnatal growth and protein turnover in four muscles of the rat. Muscle Nerve 7: 235–242, 1984.
 170. Kim, S. K., and P. P. Arisumi. The synthesis of amylase in parotid glands of young and old rats. Mech. Ageing Dev. 31: 257–266, 1985.
 171. Kim, S. K., and D. W. Calkins. Secretory protein synthesis in parotid glands of young and old rats. Arch. Oral Biol. 28: 1–4, 1983.
 172. Kim, S. K., D. W. Calkins, P. A. Weinhold, and S. S. Han. Changes in the synthesis of exportable and nonexportable proteins in parotid glands during aging. Mech. Ageing Dev. 18: 239–250, 1982.
 173. Kim, S. K., L. M. Cuzzort, and E. D. Allen. Effects of age on diabetes‐ and insulin‐induced changes in pancreatic levels of α‐amylase and its mRNA. Mech. Ageing Dev. 58: 151–161, 1991.
 174. Kim, S. K., L. M. Cuzzort, and R. K. McKean. Amylase mRNA synthesis and ageing in rat parotid glands following isoproterenol‐stimulated secretion. Arch. Oral Biol. 37: 349–354, 1992.
 175. Kim, S. K., P. A. Weinhold, D. W. Calkins, and V. W. Hartog. Comparative studies of the age‐related changes in protein synthesis in the rat pancreas and parotid gland. Exp. Gerontol. 16: 91–99, 1981.
 176. Kim, S. K., P. A. Weinhold, S. S. Han, and D. J. Wagner. Age‐related decline in protein synthesis in the rat parotid gland. Exp. Gerontol. 15: 77–85, 1980.
 177. Kimball, K. A., L. E. Cornett, E. Seifen, and R. H. Kennedy. Aging: changes in cardiac α1 ‐ adrenoceptor responsiveness and expression. Eur. J. Pharmacol. Mol. Pharmacol. 208: 231–238, 1991.
 178. Kimball, S. R., T. C. Vary, and L. S. Jefferson. Age‐dependent decrease in the amount of eukaryotic initiation factor 2 in various rat tissues. Biochem. J. 286: 263–268, 1992.
 179. Kitraki, E., E. Bozas, H. Philippidis, and F. Stylianopoulou. Aging‐related changes in IGF‐II and c‐fos gene expression in the rat brain. Int. J. Dev. Neurosci. 11: 1–9, 1993.
 180. Kittur, S. D., L. Song, H. Endo, and W. H. Adler. Nerve growth factor receptor gene expression in human peripheral blood lymphocytes in aging. J. Neurosci. Res. 32: 444–448, 1992.
 181. Krawczyk, Z., and N. Szymik. Effect of age and busulphan treatment on the hsp70 gene‐related transcript level in rat testes. Int. J. Androl. 12: 72–79, 1989.
 182. Kreamer, W., N. Zorich, D. S. Liu, and A. Richardson. Effect of age on RNA synthesis by rat hepatocytes. Exp. Gerontol. 14: 27–36, 1979.
 183. Kristal, B. S., and B. P. Yu. The next frontier: studies of the effects of age and diet on mammalian gene expression. Age Nutr. 3: 217–224, 1992.
 184. Kristal, B. S., C. C. Conrad, A. Richardson, and B. P. Yu. Is poly(A) tail length altered by aging or dietary restriction? Gerontology 39: 152–162, 1993.
 185. Kumazaki, T., M. Kobayashi, and Y. Mitsui. Enhanced expression of fibronectin during in vivo cellular aging of human vascular endothelial cells and skin fibroblasts. Exp. Cell Res. 205: 396–402, 1993.
 186. Kurtz, D. I. The effect of ageing on in vitro fidelity of translation in mouse liver. Biochim. Biophys. Acta 407: 479–484, 1975.
 187. Kurtz, D. I. A decrease in the number of active mouse liver ribosomes during aging. Exp. Gerontol. 13: 397–402, 1978.
 188. Lamb, P., and S. McKnight. Diversity and specificity in transcriptional regulation: the benefits of heterotypic dimerization. TIBS 16: 417–422, 1991.
 189. Lapchak, P. A., D. M. Araujo, K. D. Beck, C. E. Finch, S. A. Johnson, and F. Hefti. BDNF and trkB mRNA expression in the hippocampal formation of aging rats. Neurobiol. Aging 14: 121–126, 1993.
 190. Larkfors, L., T. Ebendal, S. R. Whittemore, H. Persson, B. Hoffer, and L. Olson. Decreased level of nerve growth factor (NGF) and its messenger RNA in the aged rat brain. Mol. Brain Res. 3: 55–60, 1987.
 191. Laughrea, M., and J. Latulippe. The poly(U) translational capacity of Fischer 344 rat liver does not deteriorate with age and is not affected by dietary regime. Mech. Ageing Dev. 45: 137–143, 1988.
 192. Lavie, L., A. Z. Reznick, and D. Gershon. Decreased protein and puromycinil‐peptide degradation in livers of senescent mice. Biochem. J. 202: 47–51, 1982.
 193. Lawrence, A. E., J. Z. Readinger, R. W. Ho, S. Ackley, M. Hollander, and L. L. Mays. Age‐related changes in lysine isoacceptor proportions and acylation capacity of rat liver transfer RNAs with little change in physical properties. Age 2: 56–62, 1979.
 194. Layman, D. K., G. A. Ricca, and A. Richardson. The effect of age on protein synthesis and ribosome aggregation to messenger RNA in rat liver. Arch. Biochem. Biophys. 173: 246–254, 1976.
 195. Lee, D. Y., J. J. Hayes, D. Pruss, and A. P. Wolffe. A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 72: 73–84, 1993.
 196. Lee, S., A. Francoeur, S. Liu, and E. Wang. Tissue‐specific expression in mammalian brain, heart, and muscle of S1, a member of the elongation factor‐1α gene family. J. Biol. Chem. 267: 24064–24068, 1992.
 197. Levenbook, L., and I. Krishna. Effect of ageing on amino acid turnover and rate of protein synthesis in the blowfly Phormia regina. J. Insect Physiol. 17: 9–12, 1971.
 198. Lewis, S. E., D. F. Goldspink, J. G. Phillips, B. J. Merry, and A. M. Holehan. The effects of aging and chronic dietary restriction on whole body growth and protein turnover in the rat. Exp. Gerontol. 20: 253–263, 1985.
 199. Lewis, S. E., F. J. Kelly, and D. F. Goldspink. Pre‐ and postnatal growth and protein turnover in smooth muscle, heart and slow‐ and fast‐twitch skeletal muscles of the rat. Biochem. J. 217: 517–526, 1984.
 200. Li, D. D., Y. K. Chien, M. Z. Gu, A. Richardson, and H. T. Cheung. The age‐related decline in interleukin‐3 expression in mice. Life Sci. 43: 1215–1222, 1988.
 201. Liang, C. T., J. Barnes, H. Hanai, and M. A. Levine. Decrease in Gs protein expression may impair adenylate cyclase activation in old kidneys. Am. J. Physiol. 264 (Renal Fluid Electrolyte Physiol. 33): F770–F773, 1993.
 202. Libby, R. T. Mistranslation in bacteriophage‐infected anucleate minicells of Escherichia coli: a test for error propagation. Mech. Ageing Dev. 26: 23–35, 1984.
 203. Lin, F. K., and S. H. Chang. Differences between transfer RNA methylase activity in human diploid fibroblasts during in vitro and in vivo aging. Mech. Ageing Dev. 11: 383–392, 1979.
 204. Lin, J. L., T. Asano, Y. Shibasaki, K. Tsukuda, H. Katagiri, H. Ishihara, F. Takaku, and Y. Oka. Altered expression of glucose transporter isoforms with aging in rats—selective decrease in GluT4 in the fat tissue and skeletal muscle. Diabetologia 34: 477–482, 1991.
 205. Lindell, T. J., J. J. Duffy, and B. Byrnes. Transcription in aging: the response of rat liver nuclear RNA polymerases to cyclohexamide in vivo. Mech. Ageing Dev. 19: 63–71, 1982.
 206. Linnemann, D., H. Gaardsvoll, M. Olsen, and E. Bock. Expression of NCAM mRNA and polypeptides in aging rat brain. Int. J. Dev. Neurosci. 11: 71–81, 1993.
 207. Liu, A. Y., H. Choi, Y. Lee, and K. Y. Chen. Molecular events involved in transcriptional activation of heat shock genes become progressively refractory to heat stimulation during aging of human diploid fibroblasts. J. Cell. Physiol. 149: 560–566, 1991.
 208. Liu, D. S., R. Ekstrom, J. W. Spicer, and A. Richardson. Age‐related changes in protein, RNA and DNA content and protein synthesis in rat testes. Exp. Gerontol. 13: 197–205, 1978.
 209. Lompre, A. M., F. Lambert, E. G. Lakatta, and K. Schwartz. Expression of sarcoplasmic reticulum Ca2+‐ATPase and calsequestrin genes in rat heart during ontogenic development and aging. Circ. Res. 69: 1380–1388, 1991.
 210. Madsen, H. O., K. Poulsen, O. Dahl, B. F. Clark, and J. P. Hjorth. Retropseudogenes constitute the major part of the human elongation factor la gene family. Nucleic Acids Res. 18: 1513–1516, 1990.
 211. Magnuson, V. L., M. Young, D. G. Schattenberg, M. A. Mancini, D. Chen, B. Steffensen, and R. J. Klebe. The alternative splicing of fibronectin pre‐mRNA is altered during aging and in response to growth factors. J. Biol. Chem. 266: 14654–14662, 1991.
 212. Mailleux, P., and J. J. Vanderhaeghen. Age‐related loss of cannabinoid receptor binding sites and mRNA in the rat striatum. Neurosci. Lett. 147: 179–181, 1992.
 213. Mainwaring, W. I. Changes in the ribonucleic acid metabolism of aging mouse tissues with particular reference to prostate gland. Biochem. J. 110: 79–86, 1968.
 214. Mainwaring, W. I. The effect of age on protein synthesis in mouse liver. Biochem. J. 113: 869–878, 1969.
 215. Makrides, S. C. Protein synthesis and degradation during aging and senescence. Biol. Rev. Camb. Philos. Soc. 58: 343–422, 1983.
 216. Makrides, S. C., and J. Goldthwaite. The content and size distribution of membrane‐bound and free polyribosomes in mouse liver during aging. Mech. Ageing Dev. 27: 111–134, 1984.
 217. Mallonee, R. J., N. E. Garrison, and C. M. Sellers. Quantity and translational efficiency of liver microsomes in young and old rats following partial hepatectomy. Comp. Biochem. Physiol. 72B: 275–281, 1982.
 218. Manjula, and R. M. Sundari. Variation in transfer ribonucleic acid population in liver of young, adult, and old female albino rats. Indian J. Biochem. Biophys. 18: 192–197, 1981.
 219. Marcus, D. L., N. G. Ibrahim, and M. L. Freedman. Age‐related decline in the biosynthesis of mitochondrial inner membrane proteins. Exp. Gerontol. 17: 333–341, 1982.
 220. Marcus, D. L., G. Lew, N. Gruenspecht‐Faham, and M. L. Freedman. Effect of inhibitors and stimulators on isolated liver cell mitochondrial protein synthesis from young and old rats. Exp. Gerontol. 17: 429–435, 1982.
 221. Mariotti, D., and R. Ruscitto. Age‐related changes of accuracy and efficiency of protein synthesis machinery in rat. Biochim. Biophys. Acta 475: 96–102, 1977.
 222. Martin, H., and R. Martin. RNA metabolism and ageing. Akt. Gerontol. 7: 247–252, 1977.
 223. Martinoli, M. G., J. Ouellet, E. Rháeaume, and G. Pelletier. Growth hormone and somatostatin gene expression in adult and aging rats as measured by quantitative in situ hybridization. Neuroendocrinology 54: 607–615, 1991.
 224. Masoro, E. J. Nutrition and aging: a current assessment. J. Nutr. 115: 842–848, 1985.
 225. Masoro, E. J. Food restriction in rodents: an evaluation of its role in the study of aging. J. Gerontol. 43: B59–B64, 1988.
 226. Masoro, E. J. Retardation of aging processes by food restriction: an experimental tool. Am. J. Clin. Nutr. 55: 1250S–1252S, 1992.
 227. Matocha, M. F., J. W. Cosgrove, J. R. Atack, and S. I. Rapoport. Selective elevation of c‐myc transcript levels in the liver of the aging fischer‐344 rat. Biochem. Biophys. Res. Commun. 147: 1–7, 1987.
 228. Mays, L. L., A. E. Lawrence, R. W. Ho, and S. Ackley. Age‐related changes in function of transfer ribonucleic acid of rat livers. FASEB J. 38: 1984–1988, 1979.
 229. Mays, P. K., R. J. McAnulty, and G. J. Laurent. Age‐related changes in rates of protein synthesis and degradation in rat tissues. Mech. Ageing Dev. 59: 229–241, 1991.
 230. Mays‐Hoopes, L., W. Chao, H. C. Butcher, and R. C. Huang. Decreased methylation of the major mouse long interspersed repeated DNA during aging and in myeloma cells. Dev. Genet. 7: 65–73, 1986.
 231. Mays‐Hoopes, L. L., Macromolecular methylation during aging. In: Review of Biological Research in Aging, edited by M. Rothstein. New York: Alan R. Liss, 1985, p. 361–393.
 232. Mays‐Hoopes, L. L. DNA methylation in aging and cancer. J. Gerontol. 44: 35–36, 1989.
 233. Mays‐Hoopes, L. L., A. Brown, and R. C. Huang. Methylation and rearrangement of mouse intracisternal A particle genes in development, aging, myeloma. Mol. Cell. Biol. 3: 1371–1380, 1983.
 234. Mays‐Hoopes, L. L., G. Cleland, J. Bochantin, D. Kalunian, J. Miller, W. Wilson, M. K. Wond, and D. Johnson. Function and fidelity of aging tRNA: in vivo acylation, analog discrimination, synthetase binding, and in vitro translation. Mech. Ageing Dev. 22: 135–149, 1983.
 235. McKay, J. J., R. S. Daniels, and A. R. Hipkiss. Breakdown of aberrant protein in rabbit reticulocytes decreases with cell age. Biochem. J. 188: 279–283, 1980.
 236. McMartin, D. N., and L. M. Schedbauer. Incorporation of [14C] leucine into protein and tubulin by brain slices from young and old mice. J. Gerontol. 30: 132–136, 1975.
 237. Medvedev, Z. A., Chromatin proteins and cellular ageing. In: Biomedical and Morphological Aspects of Ageing, edited by J. W. Rohen, 1981, p. 125–148.
 238. Medvedev, Z. A. Age changes of chromatin. A review. Mech. Ageing Dev. 28: 139–154, 1984.
 239. Medvedev, Z. A., Age‐related changes of transcription and RNA processing. In: Drugs and Aging, edited by D. Platt. New York: Springer‐Verlag 1986, p. 1–19.
 240. Meerson, F. Z., M. P. Javich, and M. I. Lerman. Decrease in the rate of RNA and protein synthesis and degradation in the myocardium under long‐term compensatory hyperfunction and on aging. J. Mol. Cell. Cardiol. 10: 145–159, 1978.
 241. Menzies, R. A., and P. H. Gold. The apparent turnover of mitochondria, ribosomes and sRNA of the brain in young adult and aged rats. J. Neurochem. 19: 1671–1683, 1972.
 242. Menzies, R. A., G. D. Press, and B. L. Strehler. Nucleic acid synthesis by old and young adult rat marrow cells in vitro. Biochim. Biophys. Acta 145: 178–180, 1967.
 243. Merry, B. J., and A. M. Holehan. Effect of age and restricted feeding on polypeptide chain assembly kinetics in liver protein synthesis in vivo. Mech. Ageing Dev. 58: 139–150, 1991.
 244. Merry, B. J., A. M. Holehan, S. E. Lewis, and D. F. Goldspink. the effects of ageing and chronic dietary restriction on in vivo hepatic protein synthesis in the rat. Mech. Ageing Dev. 39: 189–199, 1987.
 245. Merry, B. J., S. E. Lewis, and D. F. Goldspink. The influence of age and chronic restricted feeding on protein synthesis in the small intestine of the rat. Exp. Gerontol. 27: 191–200, 1992.
 246. Mesco, E. R., J. A. Joseph, M. J. Blake, and G. S. Roth. LOSS of D2 receptors during aging is partially due to decreased levels of mRNA. Brain Res. 545: 355–357, 1991.
 247. Mhatre, M. C., G. Fernandes, and M. K. Ticku. Aging reduces the mRNA of α1 GABAA receptor subunit in rat cerebral cortex. Eur. J. Pharmacol. Mol. Pharmacol. 208: 171–174, 1991.
 248. Miller, J. K., R. Bolla, and W. D. Denckla. Age‐associated changes in initiation of ribonucleic acid synthesis in isolated rat liver nuclei. Biochem. J. 188: 55–60, 1980.
 249. Millward, D. J. The regulation of muscle‐protein turnover in growth and development. Biochem. Soc. Trans. 6: 494–499, 1978.
 250. Minty, A. J., and F. Gross. Coding potential of non‐polyadenylated messenger RNA in mouse friend cells. J. Mol. Biol. 139: 61–83, 1980.
 251. Miyamura, Y., R. Tawa, A. Koizumi, Y. Uehara, A. Kurishita, H. Sakurai, S. Kamiyama, and T. Ono. Effects of energy restriction on age‐associated changes of DNA methylation in mouse liver. Mutat. Res. 295: 63–69, 1993.
 252. Mohan, S., and E. Radha. Age related changes in muscle protein degradation. Mech. Ageing Dev. 7: 81–87, 1978.
 253. Moldave, K., J. Harris, W. Sabo, and I. Sadnik. Protein synthesis and aging: studies with cell‐free mammalian systems. FASEB J. 38: 1979–1983, 1979.
 254. Moore, R. E., T. L. Goldsworthy, and H. C. Pitol. Turnover of 3'‐polyadenylate‐containing RNA in livers from aged, partially hepatectomized, neonatal, and Morris 5123C hepatoma‐bearing rats. Cancer Res. 40: 1449–1457, 1980.
 255. Mori, N., K. Hiruta, Y. Funatsu, and S. Goto. Codon recognition fidelity of ribosomes at the first and second positions does not decrease during aging. Mech. Ageing Dev. 22: 1–10, 1983.
 256. Mori, N., D. Mizuno, and S. Goto. Conservation of ribosomal fidelity during ageing. Mech. Ageing Dev. 10: 379–398, 1979.
 257. Mortimore, G. E., and A. R. Poso. Intracellular protein catabolism and its control during nutrient deprivation and supply. Annu. Rev. Nutr. 7: 539–564, 1987.
 258. Mosoni, L., M.‐L. Houlier, P. P. Mirand, G. Bayle, and J. Grizard. Effect of amino acids alone or with insulin on muscle and liver protein synthesis in adult and old rats. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E614–E620, 1993.
 259. Mote, P. L, J. M. Grizzle, R. L. Walford, and S. R. Spindler. Age‐related down regulation of hepatic cytochrome P1‐450, P3‐450, catalase and CuZn‐superoxide dismutase RNA. Mech. Ageing Dev. 53: 101–110, 1990.
 260. Mote, P. L., J. M. Grizzle, R. L. Walford, and S. R. Spindler. Influence of age and caloric restriction on expression of hepatic genes for xenobiotic and oxygen metabolizing enzymes in the mouse. J. Gerontol. 46: B95–B100, 1991a.
 261. Mote, P. L., J. M. Grizzle, R. L. Walford, and S. R. Spindler. Aging alters hepatic expression of insulin receptor and c‐jun mRNA in the mouse. Mutat. Res. 256: 7–12, 1991b.
 262. Moudgil, P. G., J. R. Cook, and D. E. Buetow. The proportion of ribosomes active in protein synthesis and the content of polyribosomal poly(A)‐containing RNA in adult and senescent rat livers. Gerontology 25: 322–326, 1979.
 263. Murty, C. V., M. A. Mancini, B. Chatterjee, and A. K. Roy. Changes in transcriptional activity and matrix association of α2u‐globulin gene family in the rat liver during maturation and aging. Biochim. Biophys. Acta 949: 27–34, 1988.
 264. Nagel, J. E., R. K. Chopra, F. J. Chrest, M. T. McCoy, E. L. Schneider, N. J. Holbrook, and W. H. Adler. Decreased proliferation, interleukin 2 synthesis, and interleukin 2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin‐stimulated cells from elderly donors. J. Clin. Invest. 81: 1096–1102, 1988.
 265. Nakamura, K., P. H. Duffy, M.‐H. Lu, A. Turturro, and R. W. Hart. The effect of dietary restriction on MYC protoon‐cogene expression in mice: a preliminary study. Mech. Ageing Dev. 48: 199–205, 1989.
 266. Nakazawa, T., N. Mori, and S. Goto. Functional deterioration of mouse liver ribosomes during aging: translational activity and activity for formation of the 47S initiation complex. Mech. Ageing Dev. 26: 241–251, 1984.
 267. Nelson, J. F., M. Bender, and B. S. Schachter. Age‐related changes in proopiomelanocortin messenger ribonucleic acid levels in hypothalamus and pituitary of female C57BL/6J mice. Endocrinology 123: 340–344, 1988.
 268. Neumeister, J. A., and G. C. Webster. Changes in the levels and the rate of synthesis of transfer RNA in tissues of mice of different ages. Mech. Ageing Dev. 16: 319–326, 1981.
 269. Niedermuller, H. Effects of aging on the recycling via the pentose cycle on the kinetics of glycogen and protein metabolism in various organs of the rat. Arch. Gerontol. Geriatr. 5: 305–316, 1986.
 270. Niedzwiecki, A., and J. E. Fleming. Changes in protein turnover after heat shock are related to accumulation of abnormal proteins in aging Drosophila melanogaster. Mech. Ageing Dev. 52: 295–304, 1990.
 271. Obenrader, M., J. Chen, P. Ove, and A. I. Lansing. Functional regeneration in liver of old rats after partial hepatectomy. Exp. Gerontol. 9: 181–190, 1974.
 272. Obled, C., and M. Arnal. Age‐related changes in whole‐body amino acid kinetics and protein turnover in rats. J. Nutr. 121: 1990–1998, 1991.
 273. Ogo, A., M. Haji, M. Ohashi, and H. Nawata. Decreased expression of cytochrome P450 17α‐hydroxylase mRNA in senescent bovine adrenal gland. Gerontology 37: 262–271, 1991.
 274. Ogrodnik, J. P., J. H. Wulf, and R. G. Cutler. Altered protein hypothesis of mammalian ageing processes‐II. Discrimination ratio of methionine vs. ethionine in the synthesis of ribosomal protein and RNA of C57BL/6J mouse liver. Exp. Gerontol. 10: 119–136, 1975.
 275. Oka, Y., T. Asano, K. Tsukuda, H. Katagiri, H. Ishihara, K. Inukai, and Y. Yazaki. Expression of glucose transporter isoforms with aging. Gerontology 38: 3–9, 1992.
 276. Okada, A. A., and J. F. Dice. Altered degradation of intracellular proteins in aging human fibroblasts. Mech. Ageing Dev. 26: 341–356, 1984.
 277. Ono, T., and R. G. Cutler. Age‐dependent relaxation of gene repression. Increase of endogenous murine leukemia virus‐related RNA in brain and liver of mice. Proc. Natl. Acad. Sci. U.S.A. 75: 4431–4435, 1978.
 278. Ono, T., R. Dean, S. K. Chattopadhyay, and R. G. Cutler. Dysdifferentiative nature of aging: age‐dependent expression of MULV and globin genes in thymus, liver and brain in the AKR mouse strain. Gerontology 31: 362–372, 1985.
 279. Ono, T., N. Takahashi, and S. Okada. Age‐associated changes in DNA methylation and mRNA level of the c‐myc gene in spleen and liver of mice. Mutat. Res. 219: 39–50, 1989.
 280. Ono, T., R. Tawa, K. Shinya, S. Hirose, and S. Okada. Methylation of the c‐myc gene changes during aging process of mice. Biochem. Biophys. Res. Commun. 139: 1299–1304, 1986.
 281. Ono, T., S. Yamamoto, A. Kurishita, K. Yamamoto, Y. Yamamoto, Y. Ujeno, K. Sagisaka, Y. Fukui, M. Miyamoto, R. Tawa, S. Hirose, and S. Okada. Comparison of age‐asso‐ciated changes of c‐myc gene methylation in liver between man and mouse. Mutat. Res. 237: 239–246, 1990.
 282. Orgel, L. E. The maintenance of the accuracy of protein synthesis and its relevance to ageing. Proc. Natl. Acad. Sci. U.S.A. 49: 517–521, 1963.
 283. Ove, P., M. Obenrader, and A. I. Lansing. Synthesis and degradation of liver proteins in young and old rats. Biochim. Biophys. Acta 277: 211–221, 1972.
 284. Owenby, R. K., M. P. Sulberg, and B. Jacobson. Alteration of the Q family of transfer RNAs in adult Drosophila malanogaster as a function of age, nutrition, and genotype. Mech. Ageing Dev. 11: 91–103, 1979.
 285. Pagani, F., L. Zagato, D. Coviello, and C. Vergani. Alternative splicing of fibronectin pre‐mRNA during aging. Ann. N.Y. Acad. Sci. 663: 477–478, 1992.
 286. Pagani, F., L. Zagato, J. A. M. Maier, G. Ragnotti, D. A. Coviello, and C. Vergani. Expression and Alternative splicing of fibronectin mRNA in human diploid endothelial cells during aging in vitro. Biochim. Biophys. Acta 1173: 172–178, 1993.
 287. Pagani, F., L. Zagato, C. Vergani, G. Casari, A. Sidoli, and F. E. Baralle. Tissue‐specific splicing pattern of fibronectin messenger RNA precursor during development and aging in rat. J. Cell Biol. 113: 1223–1230, 1991.
 288. Pahlavani, M. A., H. T. Cheung, N. S. Cai, and A. Richardson. Influence of dietary restriction and aging and gene expression in the immune system of rats. In: Biomedical Advances in Aging, edited by A. L. Goldstein. New York: Plenum, 1990, p. 259–270.
 289. Pardue, S., K. Groshan, J. D. Raese, and M. Morrison‐Bogorad. Hsp70 mRNA induction is reduced in neurons of aged rat hippocampus after thermal stress. Neurobiol. Aging 13: 661–672, 1992.
 290. Park, G. H., and D. E. Buetow. RNA synthesis by nuclei and chromatin isolated from adult and senescent Wistar rat liver. Gerontology 36: 61–75, 1990a.
 291. Park, G. H., and D. E. Buetow. RNA synthesis by hepatocytes isolated from adult and senescent Wistar rat liver. Gerontology 36: 76–83, 1990b.
 292. Park, G. H., and D. E. Buetow. Genes for insulin‐like growth factors I and II are expressed in senescent rat tissues. Gerontology 37: 310–316, 1991.
 293. Parker, J., J. Flanagan, J. Murphy, and J. Gallant. On the accuracy of protein synthesis in Drosophila melanogaster. Mech. Ageing Dev. 16: 127–139, 1981.
 294. Peiffer, A., N. Barden, and M. J. Meaney. Age‐related changes in glucocorticoid receptor binding and mRNA levels in the rat brain and pituitary. Neurobiol. Aging 12: 475–479, 1991.
 295. Peleg, I., Z. Greenfeld, H. Cooperman, and S. Shoshan. Type I and type III collagen mRNA levels in kidney regions of old and young rats. Matrix 13: 281–287, 1993.
 296. Pluskal, M. G., M. Moreyra, R. C. Burini, and V. R. Young. Protein synthesis studies in skeletal muscle of aging rats. I. alterations in nitrogen composition and protein synthesis using a crude polyribosome and pH 5 enzyme system. J. Gerontol. 39: 385–391, 1984.
 297. Post, D. J., K. C. Carter, and J. Papaconstantinou. The effect of aging on constitutive mRNA levels and lipopolysaccharide inducibility of acute phase genes. Ann. N.Y. Acad. Sci. 621: 66–77, 1991.
 298. Prasanna, H. R., and R. S. Lane. Protein degradation in aged nematodes (Turbatrix aceti). Biochem. Biophys. Res. Commun. 86: 552–559, 1979.
 299. Pugh, B. F., and R. Tijan. Mechanism of transcriptional activation by Sp1: evidence for coactivators. Cell 61: 1187–1197, 1990.
 300. Rao, G., E. Xia, M. J. Nadakavukaren, and A. Richardson. Effect of dietary restriction on the age‐dependent changes in the expression of antioxidant enzymes in rat liver. J. Nutr. 120: 602–609, 1990.
 301. Rao, G., E. Xia, and A. Richardson. Effect of age on the expression of antioxidant enzymes in male Fischer F344 rats. Mech. Ageing Dev. 53: 49–60, 1990.
 302. Rath, P. C., and M. S. Kanungo. Age‐related changes in the expression of cytochrome P‐450 (b+e) gene in the rat after phenobarbitone administration. Biochem. Biophys. Res. Commun. 157: 1403–1409, 1988.
 303. Rath, P. C., and M. S. Kanungo. Methylation of repetitive DNA sequences in the brain during aging of the rat. FEBS Lett. 244: 193–198, 1989.
 304. Rattan, S. I. Protein synthesis and the components of protein synthetic machinery during cellular ageing. Mutat. Res. 256: 115–125, 1991.
 305. Rattan, S. I., J. Cavallius, G. K. Hartvigsen, and B. F. Clark. Amounts of active elongation factor 1 and its activity in livers of mice during aging. In: Modern Trends in Aging Research, edited by Y. Courtois et al. Rijswijk, Netherlands: INSERM‐EURAGE/Libbey, 1986, p. 135–147.
 306. Rattan, S. I., A. Derventzi, and B. F. Clark. Protein synthesis, posttranslational modifications, and aging. Ann. N.Y. Acad. Sci. 663: 48–62, 1992.
 307. Rattan, S. I., W. F. Ward, M. Glenting, L. Svendsen, B. Riis, and B. F. Clark. Dietary calorie restriction does not affect the levels of protein elongation factors in rat livers during ageing. Mech. Ageing Dev. 58: 85–91, 1991.
 308. Reis, R. J. Ribosomes from aging mice are not generally deficient in cell‐free protein synthesis. Mech. Ageing Dev. 17: 311–320, 1981.
 309. Reitz, M. S., Jr., and D. R. Sanadi. An aspect of translational control of protein synthesis in aging: changes in the isoaccepting forms of tRNA in Turbatrix aceti. Exp. Gerontol. 7: 119–129, 1972.
 310. Reznick, A. Z., and D. Gershon. The effect of age on the protein degradation system in the nematode Turbatrix aceti. Mech. Ageing Dev. 11: 403–415, 1979.
 311. Reznick, A. Z., L. Lavie, H. E. Gershon, and D. Gershon. Age‐associated accumulation of altered FDP aldolase B in mice. FEBS Lett. 128: 221–224, 1981.
 312. Ricca, G. A., D. S. Liu, J. J. Coniglio, and A. Richardson. Rates of protein synthesis by hepatocytes isolated from rats of various ages. J. Cell Physiol. 97: 137–146, 1978.
 313. Richardson, A., The relationship between aging and protein synthesis, In: CRC Handbook of Biochemistry in Aging, edited by J. R. Florini. Boca Raton, FL: CRC Press, 1981, p. 79–101.
 314. Richardson, A., The effect of age and nutrition on protein synthesis by cells and tissues from mammals. In: CRC Handbook of Nutrition and Aging, edited by R. R. Watson. Boca Raton, FL: CRC Press, 1985, p. 31–48.
 315. Richardson, A., and M. C. Birchenall‐Sparks. Age‐related changes in protein synthesis. In: Biological Research in Aging, edited by M. Rothstein. New York: Alan R. Liss, 1983, p. 255–273.
 316. Richardson, A., and H. T. Cheung. The relationship between age‐related changes in gene expression, protein turnover, and the responsiveness of an organism to stimuli. Life Sci. 31: 605–613, 1982.
 317. Richardson, A., and J. Myers. A comparison of the cell‐free protein synthetic activities of testicular tissue obtained from rats and mice of various ages. Comp. Biochem. Physiol. 71B: 709–712, 1982.
 318. Richardson, A., and I. Semsei. Effect of aging on translation and transcription. In: Review of Biological Research in Aging, vol. 3, edited by M. Rothstein. New York: Alan R. Liss, 1987, p. 467–483.
 319. Richardson, A., M. C. Birchenallnm‐Sparks, and J. L. Staecker. Aging and transcription. In: Biological Research in Aging, edited by M. Rothstein. New York: Alan R. Liss, 1983, p. 275–294.
 320. Richardson, A., M. C. Birchenall‐Sparks, J. L. Staecker, J. Hardwick, and D. S. Liu. The transcription of various types of ribonucleic acid by hepatocytes isolated from rats of various ages. J. Gerontol. 37: 666–672, 1982.
 321. Richardson, A., J. A. Butler, M. S. Rutherford, I. Semsei, M. Z. Gu, G. Fernandes, and W. H. Chiang. Effect of age and dietary restriction on the expression of α2u‐globulin. J. Biol. Chem. 262: 12821–12825, 1987.
 322. Richardson, A., M. S. Roberts, and M. S. Rutherford. Aging and gene expression. In: Review Biological Research in Aging, vol. 2, edited by M. Rothstein. New York: Alan R. Liss, 1985, p. 395–419.
 323. Richardson, A., M. S. Rutherford, M. C. Birchenall‐Sparks, M. S. Roberts, W. T. Wu, and H. T. Cheung. Levels of specific messenger RNA species as a function of age. In: Molecular Biology of Aging: Gene Stability and Gene Expression, edited by R. S. Sohal, L. Birnbaum, and R. G. Cutler. New York: Raven Press, 1985, p. 229–241.
 324. Richter, V. Turnover of lipogenic enzymes of rat liver in dependence on age. Acta. Biol. Med. Germ. 36: 1833–1836, 1977.
 325. Ricketts, W. G., M. C. Birchenall‐Sparks, J. P. Hardwick, and A. Richardson. Effect of age and dietary restriction on protein synthesis by isolated kidney cells. J. Cell. Physiol. 125: 492–498, 1985.
 326. Riis, B., S. I. Rattan, J. Cavallius, and B. F. Clark. Levels of active elongation factor‐2 in rat livers during ageing. In: The Liver, Metabolism and Ageing, edited by K. W. Woodhouse, C. Yelland, and O. F. W. James. Rijswijk, Netherlands: INSERM‐EURAGE/Libbey, 1989, p. 117–124.
 327. Roberts, D. M., and P. Griminger. Studies concerning the protein metabolism of primary kidney cells isolated from rats of various ages. Fed. Proc. 37: 884, 1978.
 328. Rockstein, M., and G. T. Baker. Effects of X‐irradiation of pupae on aging of the thoracic flight muscle of the adult house fly Musca domestica 1. Mech. Ageing Dev. 3: 271–278, 1974.
 329. Rodriguez, C., A. Menendez‐Pelaez, K. A. Howes, and R. J. Reiter. Age and food restriction alter the porphyrin concentration and mRNA levels for 5‐aminolevulinate synthase in rat harderian gland. Life Sci. 51: 1891–1897, 1992.
 330. Rothstein, M. The formation of altered enzymes in ageing animals. Mech. Ageing Dev. 9: 197–202, 1979.
 331. Rothstein, M., Enzymes and altered proteins. In: Biochemical Approaches to Aging, edited by M. Rothstein. New York: Academic Press, 1982, p. 213–255.
 332. Rothstein, M., Enzymes, enzyme alteration, and protein turnover. In: Review of Biological Research in Aging, edited by M. Rothstein. New York: Alan R. Liss, 1983, p. 305–314.
 333. Rothstein, M., and S. C. Seifert. RNA synthesis. In: Handbook of Biochemistry in Aging, edited by J. R. Florini. Boca Raton, FL: CRC Press, 1981, p. 51–63.
 334. Roy, A. K., S. T. Nath, N. M. Motwani, and B. Chatterjee. Age‐dependent regulation of the polymorphic forms of α2u‐globulin. J. Biol. Chem. 258: 10123–10127, 1983.
 335. Salih, M. A., D. C. Herbert, and D. N. Kalu. Evaluation of the molecular and cellular basis for modulation of thyroid c‐cell hormones by aging and food restriction. Mech. Ageing Dev. 70: 1–21, 1993.
 336. Samis, H. V., V. J. Wulff, and J. A. Falzone. The incorporation of [H‐3]‐cytidine into ribonucleic acid of liver nuclei of young and old rats. Biochim. Biophys. Acta 91: 223–232, 1964.
 337. Sato, A. I., E. L. Schneider, and D. B. Danner. Aberrant gene expression and aging: examination of tissue‐specific mRNAs in young and old rats. Mech. Ageing Dev. 54: 1–12, 1990.
 338. Savu, L., R. Vranckx, M. Rouaze‐Romet, M. Maya, E. A. Nunez, J. Tréton, and I. L. Flink. A senescence up‐regulated protein: the rat thyroxine‐binding globulin (TBG). Biochim. Biophys. Acta 1097: 19–22, 1991.
 339. Sawada, N. Hepatocytes from old rats retain responsiveness of c‐myc expression to EGF in primary culture but do not enter s phase. Exp. Cell Res. 181: 584–588, 1989.
 340. Semsei, I., S. Ma, and R. G. Cutler. Tissue and age specific expression of the myc proto‐oncogene family throughout the life span of the C57BL/6J mouse strain. Oncogene 4: 465–471, 1989.
 341. Sensei, I., G. Rao, and A. Richardson. Changes in the expression of superoxide dismutase and catalase as a function of age and dietary restriction. Biochem. Biophys. Res. Commun. 164: 620–625, 1989.
 342. Semsei, I., G. Rao, and A. Richardson. Expression of superoxide dismutase and catalase in rat brain as a function of age. Mech. Ageing Dev. 58: 13–19, 1991.
 343. Semsei, I., F. Szeszak, and I. Zs.‐Nagy. In vivo studies on the age‐dependent decrease of the rates of total and mRNA synthesis in the brain cortex of rats. Arch. Gerontol. Geriatr. 1: 29–42, 1982.
 344. Seshadri, T., and J. Campisi. Repression of c‐fos transcription and an altered genetic program in senescent human fibroblasts. Science 247: 205–209, 1990.
 345. Shain, S. A., and A. L. Moss. Aging in the AXC rat: equivalence of the rates of inactivation of L‐ornithine decarboxylase and S‐adenosyl‐L‐methionine decarboxylase in prostate of young and aged rats. Endocrinology 109: 1192–1195, 1981.
 346. Sharma, H. K., H. R. Prassana, R. S. Lane, and M. Rothstein. The effect of age on enolase turnover in the free‐living nematode, Turbatrix aceti. Arch. Biochem. Biophys. 194: 275–282, 1979.
 347. Sharp, G. S., S. Lassen, S. Shankman, J. W. Hazlet, and M. S. Kendis. Studies of protein retention and turnover using nitrogen‐15 as a tag. J. Nutr. 63: 155–162, 1957.
 348. Shepherd, J. C. W., U. Walldorf, P. Hug, and W. J. Gehring. Fruit flies with additional expression of elongation factor EF‐1α live longer. Proc. Natl. Acad. Sci. U.S.A. 86: 7520–7521, 1989.
 349. Shikama, N., R. Ackermann, and C. Brack. Protein synthesis elongation factor EF‐1α expression and longevity in Drosophila melanogaster. Proc. Natl. Acad. Sci. U.S.A. In press, 1994.
 350. Sierra, F., S. Coeytaux, M. Juillerat, C. Ruffieux, J. Gauldie, and Y. Guigoz. Serum T‐kininogen levels increase two to four months before death. J. Biol. Chem. 267: 10665–10669, 1992.
 351. Sierra, F., G. H. Fey, and Y. Guigoz. T‐kininogen gene expression is induced during aging. Mol. Cell. Biol. 9: 5610–5616, 1989.
 352. Sikora, E., B. Kaminska, E. Radziszewska, and L. Kaczmarek. Loss of transcription factor AP‐1 DNA binding activity during lymphocyte aging in vivo. FEBS Lett. 312: 179–182, 1992.
 353. Singh, A., S. Singh, and M. S. Kanungo. Conformation and expression of the albumin gene of young and old rats. Mol. Biol. Rep. 14: 251–254, 1990.
 354. Singh, S., and M. S. Kanungo. Changes in expression and CRE binding proteins of the fibronectin gene during aging of the rat. Biochem. Biophys. Res. Commun. 193: 440–445, 1993.
 355. Singhal, R. P., and R. A. Kopper. Changes in transfer RNAs in development and aging. FASEB J. 39: 20–23, 1980.
 356. Singhal, R. P., R. A. Kopper, S. Nishimura, and N. Shindo‐Okada. Modification of guanine to queuine in transfer RNAs during development and aging. Biochem. Biophys. Res. Commun. 99: 120–126, 1981.
 357. Singhal, R. P., L. L. Mays‐Hoopes, and G. L. Eichhorn. DNA methylation in aging of mice. Mech. Ageing Dev. 41: 199–210, 1987.
 358. Slagboom, P. E., W. J. de Leeuw, and J. Vijg. mRNA levels and methylation patterns of the tyrosine aminotransferase gene in aging inbred rats. FEBS Lett. 269: 128–130, 1990a.
 359. Slagboom, P. E., W. J. de Leeuw, and J. Vijg. Messenger RNA levels and methylation patterns of GAPDH and β‐actin genes in rat liver, spleen and brain in relation to aging. Mech. Ageing Dev. 53: 243–257, 1990b.
 360. Slagboom, P. E., A. G. Uitterlinden, and J. Vijg. Methylation status of cKi‐ras and MHC genes in rat pituitary glands during aging and tumorigenesis. Aging 3: 141–146, 1991.
 361. Smith, C. D., J. M. Carney, P. E. Starke‐Reed, C. N. Oliver, E. R. Stadtman, R. A. Floyd, and W. R. Markesbery. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc. Natl. Acad. Sci. U.S.A. 88: 10540–10543, 1991.
 362. Sobel, H., and R. Bowman. Protein metabolism in aging mice. J. Gerontol. 26: 558–560, 1971.
 363. Sojar, H. T., and M. Rothstein. Protein synthesis by liver ribosomes from aged rats. Mech. Ageing Dev. 35: 47–57, 1986.
 364. Song, C. S., T. R. Rao, W. F. Demyan, M. A. Mancini, B. Chatterjee, and A. K. Roy. Androgen receptor messenger ribonucleic acid (mRNA) in the rat liver: changes in mRNA levels during maturation, aging, and calorie restriction. Endocrinology 128: 349–356, 1991.
 365. Song, L., J. M. Stephens, S. Kittur, G. D. Collins, J. E. Nagel, P. H. Pekala, and W. H. Adler. Expression of c‐fos, c‐jun, and jun B in peripheral blood lymphocytes from young and elderly adults. Mech. Ageing Dev. 65: 149–156, 1992.
 366. Sonntag, W. E., V. W. Hylka, and J. Meites. Growth hormone restores protein synthesis in skeletal muscle of old rats. J. Gerontol. 40: 689–694, 1985.
 367. Sonntag, W. E., J. E. Lenham, and R. L. Ingram. Effects of aging and dietary restriction on tissue protein synthesis: relationship to plasma insulin‐like growth factor‐1. J. Gerontol. 47: B159–B163, 1992.
 368. Sorger, P. K. Heat shock factor and the heat shock response. Cell 65: 363–366, 1991.
 369. Soriero, A. A. Autoradiographic study of the effect of estrogen on in vivo incorporation of [H‐3]‐uridine into uterine smooth muscle and stromal RNA in the aging ovariectomized mouse. J. Gerontol. 35: 167–176, 1980.
 370. Spindler, S. R., M. D. Crew, P. L. Mote, J. M. Grizzle, and R. L. Walford. Dietary energy restriction in mice reduces hepatic expression of glucose‐regulated protein 78 (BiP) and 94 mRNA. J. Nutr. 120: 1412–1417, 1990.
 371. Spindler, S. R., J. M. Grizzle, R. L. Walford, and P. L. Mote. Aging and restriction of dietary calories increases insulin receptor mRNA, and aging increases glucocorticoid receptor mRNA in the liver of female C3B10RF1 mice. J. Gerontol. 46: B233–B237, 1991.
 372. Stadtman, E. R. Biochemical markers of aging. Exp. Gerontol. 23: 327–347, 1988.
 373. Stadtman, E. R. Protein oxidation and aging. Science 257: 1220–1224, 1992.
 374. Stadtman, E. R., C. N. Oliver, R. L. Levine, L. Fucci, and A. J. Rivett. Implication of protein oxidation in protein turnover, aging, and oxygen toxicity. Basic Life Sci. 49: 331–339, 1988.
 375. Starke‐Reed, P. E., and C. N. Oliver. Protein oxidation and proteolysis during aging and oxidative stress. Arch. Biochem. Biophys. 275: 559–567, 1989.
 376. Starnes, J. W., R. E. Beyer, and D. W. Edington. Effects of age and cardiac work in vitro on mitochondrial oxidative phosphorilation and [3H]‐leucine incorporation. J. Gerontol. 36: 130–135, 1981.
 377. Starnes, J. W., D. W. Edington, and R. E. Beyer. Myocardial protein synthesis during aging and endurance exercise in rats. J. Gerontol. 38: 660–665, 1983.
 378. Stewart, D. A., M. R. Blackman, M. A. Kowatch, D. B. Danner, and G. S. Roth. Discordant effects of aging on prolactin and luteinizing hormone‐β messenger ribonucleic acid levels in the female rat. Endocrinology 126: 773–778, 1992.
 379. Strong, R., M. A. Moore, C. Hale, W. J. Burke, H. J. Armbecht, and A. Richardson. Age‐related changes in adrenal catecholamine content and tyrosine hydroxylase gene expression: effects of dietary restriction. In: Endocrine Function and Aging, edited by J. A. Armbrecht, R. Coe, and N. Wongsurawat. Berlin: Springer‐Verlag, 1990, p. 218–227.
 380. Strong, R., M. A. Moore, C. Hale, M. Wessels‐Reiker, H. J. Armbrecht, and A. Richardson. Modulation of tyrosine hydroxylase gene expression in the rat adrenal gland by age and reserpine. Brain Res. 525: 126–132, 1990.
 381. Swisshelm, K., C. M. Disteche, J. Thorvaldsen, A. Nelson, and D. Salk. Age‐related increase in methylation of ribosomal genes and inactivation of chromosome‐specific rRNA gene clusters in mouse. Mutat. Res. 237: 131–146, 1990.
 382. Takahashi, R., and S. Goto. Age‐associated accumulation of heat‐labile aminoacyl‐tRNA synthetases in mice and rats. Arch. Gerontol. Geriatr. 6: 73–82, 1987.
 383. Takahashi, R., and S. Goto. Fidelity of aminoacylation by rat‐liver tryosyl‐tRNA synthetase. Eur. J. Biochem. 178: 381–386, 1988.
 384. Takahashi, R., N. Mori, and S. Goto. Accumulation of heat‐labile elongation factor 2 in the liver of mice and rats. Exp. Gerontol. 20: 325–331, 1985a.
 385. Takahashi, R., N. Mori, and S. Goto. Alteration of aminoacyl tRNA synthetases with age: accumulation of heat‐labile enzyme molecules in rat liver, kidney and brain. Mech. Ageing Dev. 33: 67–75, 1985b.
 386. Takahashi, R., H. Schunkert, S. Isoyama, J. Y. Wei, B. Nadal‐Ginard, W. Grossman, and S. Izumo. Age‐related differences in the expression of proto‐oconogene and contractile protein genes in response to pressure overload in the rat myocardium. J. Clin. Invest. 89: 939–946, 1992.
 387. Takahashi, S., S. Kawashima, H. Seo, and N. Matsui. Age‐related changes in growth hormone and prolactin messenger RNA levels in the rat. Endocrinol. Jpn. 37: 827–840, 1990.
 388. Tas, S., and R. L. Walford. Influence of disulfide‐reducing agents on fractionation of the chromatin complex by endogenous nucleases and deoxyribonuclease I in aging mice. J. Gerontol. 37: 673–679, 1982.
 389. Tas, S., C. F. Tam, and R. L. Walford. Disulfide bonds and the structure of the chromatin complex in relation to aging. Mech. Ageing Dev. 12: 65–80, 1980.
 390. Tawa, R., S. Ueno, K. Yamamoto, Y. Yamamoto, K. Sagisaka, R. Katakura, T. Kayama, T. Yoshimoto, H. Sakurai, and T. Ono. Methylated cytosine level in human liver DNA does not decline in aging process. Mech. Ageing Dev. 62: 255–261, 1992.
 391. Thakur, M. K. Age‐related changes in the structure and function of chromatin: a review. Mech. Ageing Dev. 27: 263–286, 1984.
 392. Thakur, M. K., and J. Kaur. Estrogen‐induced synthesis of uterine proteins declines during aging. Mol. Biol. Rep. 17: 29–34, 1992a.
 393. Thakur, M. K., and J. Kaur. Methylation of DNA and its modulation by estrogen in the uterus of aging rats. Cell. Mol. Biol. 38: 525–532, 1992b.
 394. Thakur, M. K., T. Oka, and Y. Natori. Gene expression and aging. Mech. Ageing Dev. 66: 283–298, 1993.
 395. Tollefsbol, T. O., and H. J. Cohen. Decreased protein synthesis of transforming lymphocytes from aged humans. Mech. Ageing Dev. 30: 53–62, 1985.
 396. Tonna, E. A., and I. J. Singh. Autoradiographic investigation by aging mouse cartilage cells. Exp. Gerontol. 11: 231–241, 1976.
 397. Travali, S., G. Carnazzo, A. M. Distefano, P. Manciagli, C. Cosenza, E. Fidone, S. Petralia, A. Bernardini, L. Motta, and F. Stivala. Expression of cell cycle‐dependent genes and proliferative state of lymphocytes in aging. Arch. Gerontol. Geriatr. 11: 133–139, 1990.
 398. Tumer, N., C. Hale, J. Lawler, and R. Strong. Modulation of tyrosine hydroxylase gene expression in the rat adrenal gland by exercise: effects of age. Mol. Brain Res. 14: 51–56, 1992.
 399. Uauy, R., J. C. Winterer, C. Bilmazes, L. N. Haverberg, N. S. Scrimshaw, H. N. Munro, and V. R. Young. The changing pattern of whole body protein metabolism in aging humans. J. Gerontol. 33: 663–671, 1978.
 400. Uehara, Y., O. Tetsuya, A. Kurishita, H. Kokuryu, and S. Okada. Age‐dependent and tissue‐specific changes of DNA methylation within and around the c‐fos gene in mice. Oncogene 4: 1023–1028, 1989.
 401. van Bezooijen, C. F., T. Grell, and D. Knook. Albumin synthesis by liver parenchymal cells isolated from young, adult, and old rats. Biochem. Biophys. Res. Commun. 31: 513–519, 1976.
 402. van Bezooijen, C. F., T. Grell, and D. L. Knook. The effect of age on protein synthesis by isolated liver parenchymal cells. Mech. Ageing Dev. 6: 293–304, 1977.
 403. Vandenhaute, J., N. Claes‐Reckinger, and J. Delcour. Age‐related functional alteration of mouse liver ribosomes. Exp. Gerontol. 18: 355–363, 1983.
 404. Van der Vliet, P. C., and C. P. Verrijzer. Bending of DNA by transcription factors. BioEssays 15: 25–32, 1993.
 405. Vedova, F. D., F. Fumagalli, G. Sacchetti, G. Racagni, and N. Brunello. Age‐related variations in relative abundance of alternative spliced D2 receptor mRNAs in brain areas of two rat strains. Mol. Brain Res. 12: 357–359, 1992.
 406. Vinayak, M. A comparison of tRNA populations of rat liver and skeletal muscle during aging. Biochem. Int. 15: 279–285, 1987.
 407. Viskup, R. W., M. Baker, J. P. Holbrook, and R. Penniall. Age‐associated changes in activities of rat hepatocytes. I. Protein synthesis. Exp. Aging Res. 5: 487–496, 1979.
 408. Waggoner, S. M., M. Z. Gu, W. H. Chiang, and A. Richardson. The effect of dietary restriction on the expression of a variety of genes. In: Genetic Effects on Aging II, edited by D. E. Harrison. Cadwell, NJ: Telford Press, 1990, p. 255–272.
 409. Wagner, A. P., K. D. Beck, and G. Reck. Neural cell adhesion molecule (NCAM) and N‐cadherin mRNA during development and aging: selective reduction in the 7.4–kb and 6.7‐kb NCAM mRNA levels in the hippocampus of adult and old rats. Mech. Ageing Dev. 62: 201–208, 1992.
 410. Wallach, Z., and D. Gershon. Altered ribosomal particles in senescent nematodes. Mech. Ageing Dev. 3: 225–234, 1974.
 411. Wang, E. Characterization of the absence of an unique DNA‐binding protein in senescent but not in their young growing and nongrowing counterparts provides the means to mark the final stage of the cellular aging process. Exp. Gerontol. 27: 503–517, 1992.
 412. Wang, S., S. Zhu, J. A. Joseph, and E. E. El‐Fakahany. Comparison of the level of mRNA encoding ml and m2 muscarinic receptors in brains of young and aged rats. Neurosci. Lett. 145: 149–152, 1992.
 413. Wang, S. Y., and J. W. Rowe. Age‐related impairment in the short term regulation of insulin biosynthesis by glucose in rat pancreatic islets. Endocrinology 123: 1008–1013, 1988.
 414. Ward, W., and A. Richardson. Effect of age on liver protein synthesis and degradation. Hepatology 14: 935–948, 1991.
 415. Ward, W. F. Enhancement by food restriction of liver protein synthesis in the aging Fischer 344 rat. J. Gerontol. 43: B50–B53, 1988a.
 416. Ward, W. F. Food restriction enhancement of the proteolytic capacity of aging rat liver. J. Gerontol. 43: B121–B124, 1988b.
 417. Wattiaux, J. M., M. Libion‐Mannaert, and J. Delcour. Protein turnover and protein synthesis following actinomycin‐D injection as a function of age in Drosophila melanogaster. Gerontologia 17: 289–299, 1971.
 418. Weber, G., J. Margetan, C. E. Finch, and L. L. Mays. Brain transfer ribonucleic acid methyltransferases in young adult and old mice. Exp. Gerontol. 14: 157–160, 1979.
 419. Webster, G. C., Protein synthesis in aging organisms. In: Molecular Biology of Aging: Gene Stability and Gene Expression, edited by R. S. Sohal, L. S. Birnbaum, and R. G. Cutler. New York: Raven Press, 1985, p. 263–290.
 420. Webster, G. C., and S. L. Webster. Decreased protein synthesis by microsomes from aging Drosophila melanogaster. Exp. Gerontol. 14: 343–348, 1979.
 421. Webster, G. C., and S. L. Webster. Aminocylation of tRNA by cell‐free preparations from aging Drosophila melanogaster. Exp. Gerontol. 16: 487–494, 1981.
 422. Webster, G. C., and S. L. Webster. Decline in synthesis of elongation factor one (EF‐1) precedes the decreased synthesis of total protein in aging Drosophila melanogaster. Mech. Ageing Dev. 22: 121–128, 1983.
 423. Webster, G. C., V. T. Beachell, and S. L. Webster. Differential decrease in protein synthesis by microsomes from aging Drosophila melanogaster. Exp. Gerontol. 15: 495–497, 1980.
 424. Webster, G. C., S. L. Webster, and W. A. Landis. The effect of age on the initiation of protein synthesis in Drosophila melanogaster. Mech. Ageing Dev. 16: 71–79, 1981.
 425. Weiland, N. G., K. Scarbrough, and P. M. Wise. Aging abolishes the estradiol‐induced suppression and diurnal rhythm of proopiomelanocortin gene expression in the arcuate nucleus. Endocrinology 131: 2959–2964, 1992.
 426. Welle, S., C. Thornton, R. Jozefowicz, and M. Statt. Myofibrillar protein synthesis in young and old men. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E693–E698, 1993.
 427. Weller, E. M., M. Poot, and H. Hoehn. Induction of replicative senescence by 5‐azacytidine: fundamental cell kinetic differences between human diploid fibroblasts and NIH‐3T3 cells. Cell Prolif. 26: 45–54, 1993.
 428. Wellinger, R., and Y. Guigoz. The effect of age on the induction of tyrosine aminotransferase and tryptophan oxygenase genes by physiological stress. Mech. Ageing Dev. 34: 203–217, 1986.
 429. Wessels‐Reiker, M., C. Hale, and R. Strong. Molecular biology of information storage in the nervous system during aging. In: Memory Function and Aging‐Related Disorders, edited by J. E. Morley, R. M. Coe, R. Strong, and G. T. Grossberg. New York: Springer, 1992, p. 22–37.
 430. Wiederanders, B., and B. Oelke. The turnover of liver cytosol proteins in very old rats. Acta Biol. Med. Germ. 40: 1243–1247, 1981.
 431. Wiederanders, B., S. Ansorge, P. Bohley, H. Kirschke, J. Langner, and H. Hanson. The age dependence of intracellular proteolysis: changes of the substrate proteins. Mech. Ageing Dev. 8: 355–362, 1978.
 432. Wildenthal, K., and J. S. Crie. The role of lysosomes and lysosomal enzymes in cardiac protein turnover. FASEB J. 39: 37–41, 1980.
 433. Wilson, V. L., and P. A. Jones. DNA methylation decreased in aging but not in immortal cells. Science 220: 1055–1057, 1983.
 434. Wilson, V. L., R. A. Smith, S. Ma, and R. G. Cutler. Genomic 5‐methyldeoxycytidine decreases with age. J. Biol. Chem. 262: 9948–9951, 1987.
 435. Winterer, J. C., W. P. Steffee, W. Davy, A. Perera, R. Uauy, N. S. Scrimshaw, and V. R. Young. Whole body protein turnover in aging man. Exp. Gerontol. 11: 79–87, 1976.
 436. Wong, N. C., H. L. Schwartz, K. Strait, and J. H. Oppenheimer. Thyroid hormone‐, carbohydrate‐, and age‐dependent regulation of a methylation site in the hepatic S14 gene. Mol. Endocrinol. 3: 645–650, 1989.
 437. Wu, W. T., M. A. Pahlavani, H. T. Cheung, and A. Richardson. The effect of aging on the expression of interleukin 2 messenger ribonucleic acid. Cell. Immunol. 100: 224–231, 1986.
 438. Wust, C. J., and L. Rosen. Aminoacylation and methylation of tRNA as a function of age in the rat. Exp. Gerontol. 7: 331–343, 1972.
 439. Yang, F., W. E. Friedrichs, J. M. Buchanan, D. C. Herbert, F. J. Weaker, J. H. Brock, and B. H. Bowman. Tissue specific expression of mouse transferrin during development and aging. Mech. Ageing Dev. 56: 187–197, 1990.
 440. Young, V. R., W. P. Steffee, P. B. Pencharz, J. C. Winterer, and N. S. Scrimshaw. Total human body protein synthesis in relation to protein requirements at various ages. Nature 253: 192–194, 1975.
 441. Yousef, M. K., and H. D. Johnson. 75–Selenomethionine turnover rate during growth and aging in rats. Proc. Soc. Exp. Biol. Med. 133: 1351–1353, 1970.
 442. Zeelon, P., H. Gershon, and D. Gershon. Inactive enzyme molecules in aging organisms. Nematode fructose‐1,6‐diphosphate aldolase. Biochemistry 12: 1743–1750, 1973.
 443. Zs.‐Nagy, I., and I. Semsei. Centrophenoxine increases the rates of total and mRNA synthesis in the brain cortex of old rats: an explanation of its action in terms of the membrane hypothesis of aging. Exp. Gerontol. 19: 171–178, 1984.

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Holly Van Remmen, Walter F. Ward, Robert V. Sabia, Arlan Richardson. Gene Expression and Protein Degradation. Compr Physiol 2011, Supplement 28: Handbook of Physiology, Aging: 171-234. First published in print 1995. doi: 10.1002/cphy.cp110109