Aging is a complex and intraindividual process, usually defined as a time-dependent progressive loss of the individual’s physiological integrity, which eventually leads to deteriorated physical function.
The accumulated molecular and cellular damage across an individual’s life span often leads to age-associated pathological conditions and thus makes them more prone to disease and death.
Despite hundreds of explored and developed theories, not a single one fully and comprehensively explains the process of aging. Recently, biologic currents point to 2 main theories: programmed aging and damage or error-based theories.
The programmed aging theory suggests an intrinsic biological programmed deterioration of the structural and functional capacity of the human cells. The error-based theories highlight the cumulative damage to living organisms leading to intrinsic aging.
The world population has been progressively aging and thus raising the average life expectancy. With this life span increase and its associated aging comorbidities, there is a growing challenge to make older people physically active and functionally independent until the rest of their lives.
Regular physical activity in the older population—especially aerobic and resistance training—plays an important role at a multisystem level, preventing severe muscle atrophy, maintaining cardiorespiratory fitness and cognitive function, boosting metabolic activity, and improving or maintaining functional independence.
In a study by Rebelo Marques and colleagues, researchers summarized the specific antiaging effects of physical exercise in different cellular hallmarks.
Genomic instability is caused by exogenous (physical, chemical, and biological) and endogenous factors [deoxyribonucleic acid (DNA) replication errors, spontaneous hydrolytic reactions, and reactive oxygen species (ROS).
Exercise plays a role in maintaining genomic stability. In rodent models, aerobic exercise improves DNA repair mechanisms and nuclear factor kappa B (NF-kB).
Moreover, it augments DNA repair and decreases the number of DNA adducts (up to 77%), related to aging and several risk factors for cardiovascular diseases.
A six-month resistance training program in an institutionalized elderly population showed a tendency to reduce cell frequency with micronuclei (~15%) and the total number of micronuclei (~20%), leading to a higher resistance against genomic instability.
Telomeres are ribonucleoprotein complex structures that protect the integrity of information-carrying DNA throughout the cell cycle, preventing the base pair loss of chromosomal DNA during cellular division.
Over consecutive divisions, the telomers start losing their length, which precludes further cell division, causing cellular senescence or apoptosis. Interestingly, recent evidence supports that telomerase activation can revert aging, namely, in the premature aging of telomerase-deficient mice when the enzyme is genetically reactivated.
Exercise has been associated with an upregulation of protective proteins (such as telomeric repeat-binding factor 2) and DNA repair pathway proteins, as well as a downregulation of negative regulator proteins of cell cycle progression in middle-aged athletes.
Epigenetics studies the mitotically and/or meiotically heritable changes within the genetic function that cannot be explained by DNA sequence changes. A multiplicity of epigenetic modifications affects all tissues and cells throughout life. It studies how our behaviors and environment can cause changes that affect the way our genes work.
Chronic moderate aerobic exercise increases the methylation levels of the pro-inflammatory apoptosis-associated speck-like protein caspase gene, which modulates IL-18 and IL-1b in the aged leukocytes, thereby contributing to reduced age-related pro-inflammatory cytokines.
Loss of Proteostasis
Aging and some aging-related diseases are linked to impaired protein homeostasis, also known as proteostasis.
Aerobic exercise induces autophagy, thus preventing the loss of strength and muscle mass through the modulation of IGF-1 signaling pathway, decreasing cardiovascular disease risk, and eliminating damaging proteins triggering neurodegeneration.
Deregulated Nutrient Sensing
The growth hormone (GH) is produced by the anterior pituitary gland and is regulated by the growth hormone-releasing hormone, acting mainly in the hepatocytes to induce insulin-like growth factor 1 (IGF-1) secretion.
The effect of exercise on glucose metabolism through increased glucose transporter type 4 production is a well-known mechanism of improved insulin sensibility associated with physical activity.
The clear causal relationship between mitochondrial dysfunction and aging has long been a target of great discussion; however, the specific mechanisms involved remain unrevealed. With increasing age comes a decline in mitochondrial integrity and biogenesis because of alterations in mitochondrial dynamics and mitophagy inhibition, impairing dysfunctional mitochondria removal.
The regular practice of physical exercise has a positive impact on mitochondrial function. Regular physical exercise may maintain a pool of bioenergetically functional mitochondria that, by improving the systemic mitochondrial function, contribute to morbidity and mortality risk reduction throughout one’s life span.
Stem Cell Exhaustion
In aging, the declining regenerative potential of tissues is obvious. A good example is the age-related decline in hematopoiesis, causing a diminished production of adaptive immune cells, a process designated as immunosenescence.
The stem cells more affected by aging are myogenic, known as satellite cells. Satellite cell alterations manage the reduced replacement and repair efficiency potential in human skeletal muscle tissue myofibers. Age-reduced functionality or the number of these cells inhibits proper muscle-mass maintenance.
Animal studies showed that aerobic exercise not only promotes satellite cell pool expansion in young and old mice but also potentiates myofibers with greater numbers of satellite cells in young and old rats.
Older individuals must practice physical exercise to maintain the health-related quality of life and functional capabilities that mitigate physiological changes and comorbidities associated with aging.
Physical exercise should include aerobic exercise, muscle strengthening and endurance training, and flexibility and neuromotor exercises. Physical exercise difficulty and intensity progression should be tailored to the individual’s tolerance, preference, and specific needs.
Physical exercise is a free and easy-to-do intervention that reduces the risk of many potentially lethal diseases and helps attenuate many of the systemic and cellular effects of aging, improving the function of most of the mechanisms involved with aging.
Alexandre Rebelo-Marques, et al. Aging Hallmarks: The Benefits of Physical Exercise. 2018. Front Endocrinol. doi: 10.3389/fendo.2018.00258