Biological Theories of Aging

Biological Theories of Aging PTE 753

Programmed Theories of Aging

Aging is believed to be genetically determined, suggesting an internal clock that programs longevity.

  • Genetic Contribution:
    • Twin studies estimate that 20-30% of aging is attributable to genetics.
    • The maximum human lifespan is posited to remain unchanged, indicating a limit set by genetic factors.

Hayflick Limit

  • Refers to the phenomenon known as "replicative senescence", where cells undergo a limited number of divisions before they age and cease to divide.
  • This limitation may potentially be attributed to the shortening of telomeres, protective structures at the ends of chromosomes.
  • Studies involving telomere-deficient mice indicate that these mice age normally, suggesting additional factors may influence aging beyond telomere length.

Neuroendocrine Theory

  • Proposes that programmed functional changes in neurons along with associated hormones contribute to the aging process.
  • The hypothalamic-pituitary-adrenal axis (HPAA) is identified as a key regulator, acting as a pacemaker for aging.
  • Impairments in homeostatic mechanisms lead to conditions like somatopause, characterized by decreased growth hormone levels with age.

Immunological Theory

  • This theory suggests a functional decline of the immune system with age.
  • There is an observed increase in autoimmune phenomena, where the body begins to attack its own tissues.
  • The thymus gland, responsible for T-cell maturation, undergoes involution with age, contributing to decreased immune function.

Stochastic Theories of Aging

The stochastic perspective posits that aging results from small random changes accumulating over time, leading to failures in biological repair mechanisms.

  • Observation: Animals living in protected environments do not exhibit an increase in maximum lifespan, challenging deterministic old-age theories.

Free Radical Theory

  • Free radicals are highly reactive molecules that can damage various biomolecules.
  • Their accumulation leads to oxidative damage impacting lipids, DNA, proteins, and tissues.
  • Mitochondrial DNA has been linked to longevity; thus, its integrity is essential.
  • While reactive oxygen species are critical for cellular health, neutralizing free radicals does not necessarily correlate with increased longevity.

Energy Restriction Theory

  • The concept posits that there is a finite number of calories the body can utilize over a lifetime.
  • Energy expenditure is inversely proportional to lifespan, meaning that reduced energy expenditure may lead to longer lifespans.
  • The assertion is less compelling for primate species, indicating potential limits to extrapolation from other animal models.

Cross-linking Theory

  • This theory explains aging through the binding of glucose to proteins, leading to a deterioration in biological function.
  • Specific consequences include hardening of connective tissues, cardiac enlargement, and renal disorders.
  • In individuals with diabetes, aging appears accelerated, with these patients exhibiting 2-3 times more cross-linked proteins than non-diabetics.

Application of Aging Theories

Age-related Inflammation

Inflammation is a major mechanism linking aging to various diseases.

  • Cardiovascular Diseases:
    • Conditions may include cardiomyopathy, atherosclerosis, and stroke.
  • Neurodegenerative Diseases:
    • Includes Alzheimer's and Parkinson's diseases.
  • Chronic Inflammation:
    • Associated with metabolic disorders such as Type 2 diabetes, fatty liver disease, and sleep apnea.
  • Musculoskeletal Disorders:
    • Contributes to conditions like osteoarthritis, osteoporosis, and sarcopenia.
  • Cancer:
    • Related types include gastric, liver, lung, gall bladder, colon, rectal, pancreatic, prostate, among others.

Effects of Chronic Inflammation

  • Cardiovascular Diseases:
    • Chronic inflammation can induce arterial contraction and vasoconstriction, leading to atherosclerosis.
    • Approximately 15 to 20% of cancer-related deaths are associated with inflammatory responses; anti-inflammatory agents may reduce cancer risks.
  • Type 2 Diabetes:
    • Tied to increased circulating inflammatory mediators.
  • Bone Diseases:
    • Inflammatory cytokines are involved in bone homeostasis, increasing bone reabsorption, and are implicated in osteoarthritis.
  • Brain Dysfunction:
    • Major contributor to Alzheimer's disease pathogenesis and general cognitive decline in older populations.
  • Frailty:
    • Inflammatory processes correlate with the frailty syndrome observed in aging.

Mechanism of Age-Related Inflammation

The causes of age-related inflammation remain unidentified, though potential sources include:

  • Immune system dysregulation
  • Oxidative stress
  • Advanced glycation end products (AGEs)
  • Senescent cells

What Can Physical Therapists Do?

Physical Activity

  • Unfavorable neurotoxicity and neurodegeneration can be prevented through physical activity.
  • It can attenuate the expression of pro-inflammatory markers, indicating a role in reducing inflammation.
  • Physical activity modulates adaptive immunity, beneficial for overall immune health.
  • Particularly, it can mitigate the effects of Alzheimer’s Disease, highlighting the importance of exercise in managing age-related conditions.