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	Figure 1. Expected demographic evolution of the different population segments from 2015 to 2050. Data source: U.S. Census Bureau, 2013; International Data Base.
	Figure 2. Hallmarks of aging proposed by López‐Otín et al. 171. Abbreviations: AMPK, AMP‐activated protein kinase; DNA, deoxyribonucleic acid; GH, growth hormone; IGF‐1, insulin‐like growth factor 1; IL, interleukin; miRNA, micro ribonucleic acid; mtDNA, mitochondrial DNA; mTOR, mammalian target of rapamycin; NK, natural killer; NLRP3, NOD‐like receptor protein 3; PGC‐1, peroxisome proliferator‐activated receptor gamma coactivator 1; PTMs, posttranslational modifications; ROS, reactive oxygen species; SIRT, sirtuin; Glut 4; glucose transporter type 4; TERT, human telomerase reverse transcriptase; TNF, tumor necrosis factor.
	Figure 3. Main physiological changes leading to loss of muscle mass and functional decline in the oldest old. Abbreviations: CRP, C‐reactive protein; FSH, follicle stimulating hormone; GH, growth hormone; IGF‐1, insulin‐like growth factor; IL, interleukin; LH, luteinizing hormone; TFG‐β, transforming growth factor β; TNFα, tumor necrosis factor α.
	Figure 4. Algorithm for the diagnosis of sarcopenia and for the quantification of its severity proposed by the European Working Group on Sarcopenia in Older People 70, and available tests for its assessment. SPPB, short physical performance battery.
	Figure 5. Overview of the relationship between sarcopenia, frailty, and overall functional decline in the elderly.
	Figure 6. Relationship between the risk of functional/physiological decline during aging and the levels of physical activity.
	Figure 7. Representative example of the evolution of muscle mass during aging in a very active and a sedentary old man.
	Figure 8. Overview of the multisystem exercise benefits in the oldest old.
	Figure 9. Benefits of aerobic and resistance exercise in the elderly.
	Figure 10. Relationship between muscle protein synthesis (MPS) and breakdown (MPB) in different conditions, and potential factors that influence this relationship.
	Figure 11. Physical interventions to prevent disuse‐induced adaptations. Abbreviations: BFR, blood flow restriction; NMES, neuromuscular electrical stimulation; Vo2peak, peak oxygen consumption.

Teaching Material

P. L. Valenzuela, A. Castillo-García, J. S. Morales, M. Izquierdo, J. A. Serra-Rexach, A. Santos-Lozano, A. Lucia. Physical Exercise in the Oldest Old. Compr Physiol 9: 2019, 1281-1304.

Didactic Synopsis

Major Teaching Points:

• Aging is associated with an increased risk for intrinsic capacity decline, which is largely a result of a multisystem deterioration including changes at the endocrine, neuromuscular, metabolic, and cardiorespiratory level.
• Lifetime physical exercise can help to maintain (or at least attenuate the loss of) many of the properties (notably, muscle mass, functional ability, cardiorespiratory function) affected by aging and especially by inactive aging.
• Exercise programs are also beneficial in frail elders, including institutionalized or hospitalized individuals.
• Multicomponent exercise programs (especially if combining aerobic and resistance training) provide multiple systemic benefits, including improvements in neuromuscular, endocrine, cardiovascular, cardiorespiratory, metabolic and cognitive function.
• Exercise interventions—or alternatively, passive strategies such as neuromuscular electrical stimulation if volitional exercise is not feasible—should be implemented during disuse situations such as hospitalization.

Didactic Legends

The following legends to the figures that appear throughout the article are written to be useful for teaching.

Figure 1 Teaching points: This figure illustrates how societies are expected to age from 2015 to 2050. Particularly, the oldest old (i.e., those aged > 80 years) are expected to triple in this time period, being the most rapidly expanding population segment.

Figure 2 Teaching points: This figure illustrates the nine candidate hallmarks of aging proposed by López-Otín et al. (169). Primary hallmarks (colored in blue) are negative processes that progressively hasten aging, antagonistic hallmarks (colored in red) are necessary processes that can became negative if present in excess, and integrative hallmarks (colored in yellow) are those that directly affect tissue homeostasis and function.

Figure 3 Teaching points: This figure illustrates the multisystem physiological changes that occur with aging and that eventually result in loss of muscle mass and functional decline. Briefly, aging is characterized by a pro-inflammatory status, reduced myogenic and regenerative capacity, decreased cardiorespiratory function, impaired protein turnover, loss of muscle mass and function, impaired endocrine function (reduced anabolic response), and mitochondrial dysfunction (with subsequent oxidative stress).

Figure 4 Teaching points: This figure illustrates an algorithm for the diagnosis of sarcopenia. If an individual present with low muscle strength, which can be assessed through handgrip strength or the chair to stand test, muscle mass (ideally assessed with dual-energy X-ray absorptiometry) should be measured to confirm the presence of sarcopenia. If sarcopenia is diagnosed, the physical performance should be assessed (through walking tests or the short physical performance battery [SPPB]) to quantify the severity of this condition.

Figure 5 Teaching points: This figure illustrates the relationship between sarcopenia, frailty, and overall functional decline in the elderly. Sarcopenia refers to an excessive loss of muscle mass and function that can also affect physical performance. In contrast, frailty refers to a wider concept that not only involves sarcopenia but also a deterioration in multiple physiological systems (e.g., impaired endocrine, immune and musculoskeletal function, and also impaired cognition) that eventually result in negative consequences to physical, cognitive, and social dimensions.

Figure 6 Teaching points: This figure illustrates how the risk of functional decline in the elderly decreases with greater levels of physical activity.

Figure 7 Teaching points: This figure illustrates how lifelong physical activity can help to prevent loss of muscle quantity and quality during aging.

Figure 8 Teaching points: This figure illustrates the multisystem benefits that physical exercise provides on the oldest old. Briefly, it increases muscle mass and improves neuromuscular function, increases muscle protein turnover and energy expenditure, improves body composition, and enhances cardiovascular and respiratory function.

Figure 9 Teaching points: This figure illustrates the multisystem benefits that aerobic and resistance exercise provide in the elderly.

Figure 10 Teaching points: This figure illustrates how muscle protein synthesis (MPS) and breakdown (MPB) vary with advancing age. Aging is accompanied by a decreased anabolic response to lifestyle stimuli such as physical activity and nutrition, also known as ‘anabolic resistance’, which results in a slight imbalance in muscle protein turnover and eventually in a loss of muscle mass. In addition, in some situations such as chronic diseases or frailty, MPB can be aggravated as a result of an excessive pro-inflammatory status, which results in a further imbalance in muscle protein turnover.

Figure 11 Teaching points: This figure illustrates some physical interventions that can be implemented to prevent disuse-induced adaptations in the elderly. These interventions include both active and passive strategies, the latter being feasible even when volitional exercise cannot be performed.