Aging changes

Aging is the time-related progressive functional decline that affects all organ systems. It is believed to be caused by the accumulation of DNA damage, hormonal changes, and internally programmed cellular changes. Effects of aging include stiffening of the arteries and calcification of valves (cardiovascular system), osteoporosis and increased risk of fracture (musculoskeletal system), decreased chest wall compliance and increased ventilation-perfusion mismatch (respiratory system), susceptibility to recurrent infections and malignancies (immune system), and decline in cognitive function and changes in sleep patterns (nervous system).

All cells and all organ systems are subject to the natural processes of aging that ultimately lead to progressive functional decline. Aging is characterized by cellular degradation combined with a diminished capacity for biosynthetic processes and cellular repair mechanisms.

Effects of aging on repair and regeneration

A number of factors are associated with reduced regenerative ability during aging and contribute to the aging process, e.g.: ^[1]

• Genomic instability
  • Accumulation of genetic damage with age
  • Causative factors can be exogenous (e.g., UV light, chemical carcinogens) or endogenous (e.g., reactive oxygen species, DNA replication errors, hormonal changes).
  • These factors can reduce cellular regenerative capacity, alter gene function, and promote neoplastic transformation.
• Telomere shortening: Each cell cycle leads to a progressive decrease of telomere length; if telomere length falls beneath a certain threshold, cellular apoptosis or senescence is signalled.
• Epigenetic modifications: Research suggests that epigenetic changes (e.g., posttranslational histone modification, DNA methylation) can contribute to a decreased regenerative ability.
• Disrupted protein homeostasis: Decreased efficiency of pathways controlling proteostasis (e.g., autophagy, ubiquitin-proteasome degradation system) results in protein dysfunction and cellular damage, which in turn contributes to cellular dysfunction.
• Metabolic changes: Age-related changes in pathways responsible for nutrient sensing (e.g., mTOR pathway, mitochondrial dysfunction) can negatively impact cellular function.
• Changes in stem cell microenvironment: Aging is associated with a dysregulation of molecular mediators in the microenvironment that are necessary for proper stem cell regeneration (e.g., in muscle, intestine, CNS).

• Increased bone resorption and osteoporosis, increased risk of fracture (♀ > ♂)
  • Postmenopausal osteoporosis: decreased estrogen levels → increased bone resorption
  • Senile osteoporosis; (especially in individuals > 70 years): decreased osteoblast activity → decreased osteoid production
• Decreased lean body mass due to atrophy and loss of muscle cells (sarcopenia)
• Degenerative changes in joints: stiffer and less flexible joints, decreased synovial fluid and cartilage, calcification (e.g., in the shoulder), height loss
• Bone marrow: decreased mass, increased percentage of fat, weaker response to stimuli (e.g., ↓ hematopoiesis following blood loss)

Regular exercise and a diet rich in protein, vitamin D, creatine, and omega-3 fatty acids are essential to ensure muscle growth and help prevent sarcopenia.

Intrinsic aging

There is an increased incidence of:

• Noncancerous skin growths such as:
  • Seborrheic keratosis
  • Keratoacanthomas
• Cancerous growths such as basal cell cancer and squamous cell carcinoma
• Skin tags, warts, liver spots, solar lentigo
• Hyperpigmented macules due to cutaneous deposition of lipofuscin (typically in the face and dorsum of hand)
• Xerosis cutis and pruritus due to decreased lipid and sebum synthesis and increased moisture loss
• Heatstroke due to decreased number of sweat glands
• Wrinkles due to:
  • Decreased elastin synthesis → increased skin laxity and rigidity
  • Decreased collagen synthesis → atrophy of the dermis → wrinkle formation and decreased strength → increased risk of skin damage (e.g., decubitus and bruises)
  • Increased crosslinking of elastin and collagen → skin stiffness and decreased elastic recoil (elastosis) ^[2]
  • Decreased glycosaminoglycan (including hyaluronic acid) synthesis → decreased dermal moisture retention → decreased dermal volume
  • Decreased subdermal fat → skin sagging and risk of hypothermia
• Senile purpura: recurrent, irregularly shaped, dark purple macules
  • Progressive loss of connective tissue, subcutaneous fat, and blood vessel elasticity → extravasation of blood into the dermis
  • More common in light-skinned individuals
  • Typically develops on areas most exposed to the sun (e.g., forearms, face, neck)
  • Existing lesions will spontaneously resolve in 1–3 weeks but new lesions can occur

Extrinsic aging

• Solar elastosis
  • Age-related cutaneous change characterized by the development of diffusely thickened and wrinkled skin, sometimes with yellow discoloration
  • Caused by the accumulation of damaged collagen and elastic tissue as a result of chronic sun exposure (photoaging), especially with UVA light

• Nails
  • Become more brittle and may become yellowed
  • Toenails may become thicker
  • Ingrown toenails and onychomycosis are more common
• Hair: graying, baldness (see “Male pattern hair loss” and “Female pattern hair loss”)

• Vascular sclerosis and stiffness → ↑ systolic blood pressure
• Myocardial hypertrophy → left ventricular hypertrophy and progressive stiffening with a 10% increase in wall size → ↓ left ventricular cavity size and sigmoid-shaped interventricular septum
• Isolated atrial amyloidosis due to atrial natriuretic peptide accumulation
• Mitral and aortic valve thickening and calcification
• Increased aortic diameter
• Marked decline in stress-induced and exercise-induced maximal heart rate due to decreased response to the action of catecholamines
• Lipofuscin deposits in cardiac muscle
• Increased left atrial cavity size

• Kidneys
  • Increased susceptibility to intravascular volume depletion → prerenal acute kidney injury
  • Decreased glomerular filtration rate (GFR), diffuse sclerosis of glomeruli
  • Decreased number of nephrons
  • Decreased acid load excretion
  • Decreased renal mass and replacement of parenchyma by fat and fibrosis, predominantly in the renal cortex → decreased maximal concentrating ability
• Urinary and sexual
  • General
    • Voiding dysfunction (e.g., increased urinary frequency and urgency)
    • Increased risk of urinary tract infection
    • Decrease in libido (typically more pronounced in women than men)
  • Women
    • Postmenopausal estrogen deficiency leading to:
      • Vaginal shortening, atrophy, dryness, and irritation
      • Increased risk of yeast infections and other UTIs
      • Increased vaginal pH
      • Possibly dyspareunia
    • Decreased tone of pelvic floor muscles → prolapse of vagina, uterus, or bladder
  • Men
    • Testicular atrophy → ↓ spermatogenesis
    • Enlarged prostate gland
    • Slowed urination, erection, and ejaculation
    • Increased refractory period
  • See also “Sexuality and aging.”

• Impaired immune response and regulation of inflammation predispose individuals to recurrent infection, impaired wound healing, malignancy, and autoimmune disease.
• Decreased antibody and cell-mediated immune responses to a new antigen, which leads to:
  • A decline in the counts of most subsets of B cells and T cells (exception: memory T-cell and memory B-cell counts increase)
  • Decreased affinity of antibodies for new antigens
    • Decrease in the variety of B-cell receptors for antigens
    • Increase in the proportion of monoclonal cell lines
    • Impaired affinity maturation and impaired V(D)J recombination
• Total immunoglobulin level remains the same.
• Macrophage and neutrophil counts do not decrease but they are less effective in their functions (e.g., phagocytosis).
• Increased number of NK cells, PGE₂, and increased autoantibody production
• Immunosenescence
  • Definition: remodeling of the immune system with age, which decreases immune efficacy
  • Complications include:
    • ↑ Susceptibility to infection
    • ↓ Response to vaccination
    • ↑ Risk of inflammatory diseases

References:^{[4][5][6][7][8][9]}

• Decreasing hormones
  • Calcitonin, growth hormone, renin, aldosterone, melatonin (loss of normal circadian rhythms)
  • Estrogen and prolactin in women (e.g., contributes to breast atrophy)
  • Testosterone gradually decreases in men.
• Increasing hormones: FSH, LH, norepinephrine, parathyroid hormone (contributes to osteoporosis)

• Decreased colonic motility
• Decreased mucosal protection in the stomach
• Decreased tone of the lower esophageal sphincter

• Hearing impairments: presbycusis
• Visual impairments
  • Presbyopia
  • Decline of depth perception, contrast, and visual fields
  • Decline of vertical gaze and convergence ^[11]
• Decreased sense of smell and taste
• Reduced ability to detect vibration, touch, temperature, and pressure changes (increased risk of pressure ulcers, hypothermia, and burns)
• Decreased/absent deep tendon reflexes (e.g., ankle jerk reflex)
• Decline in balance and gait stability (e.g., slow speed, reduced tandem gait ability) leading to increased risk of falls in older adults
• Lower-extremity weakness
  • Delay in the onset of muscle activation due to a greater contraction of antagonistic muscles
  • Decline in the ability to develop joint torque using lower extremity muscles (e.g., compromised balance recovery during a postural disturbance)
  • Decline in physical function due to increased muscle tone, decreased muscle mass and increased muscle adiposity
• Decreased cerebral blood flow and brain volume (due to neuronal loss)
• Fluid intelligence declines, whereas crystallized intelligence increases.
• Altered sleep patterns in older adults: early morning awakening, later sleep onset, decreased REM, and decreased slow-wave sleep
• Psychomotor slowing
  • A state characterized by decreased and decelerated physical movements, speech, and mental processes (i.e., decline in executive function, working memory, processing speed, and attention span)
  • In most cases, no clinically significant impairment in social or occupational functioning
• Increased suicide risk in individuals with physical illness, mental illness (particularly depression), functional impairment, and stressful life events (e.g., loss of a partner)