Biology of Aging

4.

Systemic and Organismal Aging

4.1.

Immunosenescence and Inflammaging

4.1.1.

Thymic Involution

4.1.1.1.

Reduction in thymic output

4.1.1.2.

Impact on T cell diversity

4.1.1.3.

Thymic epithelial cell changes

4.1.1.4.

Adipose tissue replacement

4.1.2.

Decline in Adaptive Immunity

4.1.2.1.

T cell senescence

4.1.2.1.1.

Memory T cell accumulation

4.1.2.1.2.

Naive T cell reduction

4.1.2.1.3.

TCR repertoire contraction

4.1.2.2.

B cell dysfunction

4.1.2.2.1.

Antibody production decline

4.1.2.2.2.

Class switching defects

4.1.2.2.3.

Memory B cell changes

4.1.3.

Dysregulation of Innate Immunity

4.1.3.1.

Altered macrophage and neutrophil function

4.1.3.1.1.

Phagocytic capacity

4.1.3.1.2.

Cytokine production

4.1.3.2.

Natural killer cell changes

4.1.3.3.

Dendritic cell dysfunction

4.1.4.

Chronic Low-Grade Inflammation (Inflammaging)

4.1.4.1.

Sources of inflammation

4.1.4.1.1.

Senescent cells

4.1.4.1.2.

Gut microbiome changes

4.1.4.1.3.

4.1.4.2.

Systemic effects

4.1.4.2.1.

Acute phase response

4.1.4.2.2.

Metabolic dysfunction

4.1.5.

Autoimmunity and Aging

4.1.5.1.

Increased autoantibody production

4.1.5.2.

Molecular mimicry

4.1.5.3.

Loss of self-tolerance

4.2.

Endocrine System Aging

4.2.1.

4.2.1.1.

Hormonal changes

4.2.1.1.1.

Estrogen decline

4.2.1.1.2.

FSH and LH elevation

4.2.1.2.

Physiological consequences

4.2.1.2.1.

4.2.1.2.2.

Cardiovascular changes

4.2.1.2.3.

Cognitive effects

4.2.2.

4.2.2.1.

Decline in testosterone

4.2.2.2.

Symptoms and effects

4.2.2.2.1.

Muscle mass loss

4.2.2.2.2.

Bone density reduction

4.2.2.2.3.

4.2.3.

Somatopause (Decline in Growth Hormone)

4.2.3.1.

Changes in IGF-1 levels

4.2.3.2.

Effects on metabolism and body composition

4.2.3.2.1.

Muscle mass reduction

4.2.3.2.2.

Fat accumulation

4.2.3.2.3.

Bone metabolism

4.2.4.

Adrenopause (Decline in DHEA)

4.2.4.1.

Adrenal hormone changes

4.2.4.2.

Impact on aging

4.2.4.3.

Cortisol dysregulation

4.2.5.

Changes in Insulin Sensitivity

4.2.5.1.

Insulin resistance

4.2.5.2.

Risk of metabolic disorders

4.2.5.3.

Beta cell dysfunction

4.2.6.

Thyroid Function Changes

4.2.6.1.

4.2.6.2.

T3 and T4 alterations

4.2.6.3.

Subclinical hypothyroidism

4.3.

Musculoskeletal Aging

4.3.1.

Sarcopenia (Loss of Muscle Mass and Function)

4.3.1.1.

Mechanisms of muscle loss

4.3.1.1.1.

Protein synthesis decline

4.3.1.1.2.

Mitochondrial dysfunction

4.3.1.1.3.

Motor unit loss

4.3.1.2.

Functional consequences

4.3.1.2.1.

Strength reduction

4.3.1.2.2.

Mobility impairment

4.3.1.2.3.

4.3.1.3.

Type II fiber atrophy

4.3.2.

Osteoporosis (Loss of Bone Density)

4.3.2.1.

Bone remodeling imbalance

4.3.2.1.1.

Osteoblast dysfunction

4.3.2.1.2.

Osteoclast activation

4.3.2.2.

4.3.2.3.

Trabecular vs cortical bone loss

4.3.3.

Osteoarthritis and Cartilage Degeneration

4.3.3.1.

Cartilage breakdown

4.3.3.1.1.

Collagen degradation

4.3.3.1.2.

Proteoglycan loss

4.3.3.2.

Joint pain and stiffness

4.3.3.3.

Synovial inflammation

4.3.4.

Tendon and Ligament Changes

4.3.4.1.

Collagen cross-linking

4.3.4.2.

Reduced elasticity

4.3.4.3.

Injury susceptibility

4.4.

Cardiovascular Aging

4.4.1.

Arterial Stiffening and Atherosclerosis

4.4.1.1.

Vascular changes

4.4.1.1.1.

Elastin degradation

4.4.1.1.2.

Collagen accumulation

4.4.1.1.3.

Smooth muscle cell changes

4.4.1.2.

Plaque formation

4.4.1.2.1.

Lipid accumulation

4.4.1.2.2.

Inflammatory processes

4.4.1.3.

Endothelial dysfunction

4.4.2.

Cardiac Hypertrophy and Fibrosis

4.4.2.1.

Structural heart changes

4.4.2.1.1.

Cardiomyocyte enlargement

4.4.2.1.2.

Collagen deposition

4.4.2.2.

Impact on cardiac function

4.4.2.2.1.

Diastolic dysfunction

4.4.2.2.2.

Reduced compliance

4.4.3.

Reduced Cardiac Output

4.4.3.1.

Decline in heart performance

4.4.3.2.

Exercise intolerance

4.4.3.3.

Chronotropic incompetence

4.4.4.

Valvular Changes

4.4.4.1.

4.4.4.2.

Stenosis and regurgitation

4.5.

Neurobiological Aging

4.5.1.

Structural and Functional Brain Changes

4.5.1.1.

4.5.1.1.1.

Gray matter loss

4.5.1.1.2.

White matter changes

4.5.1.2.

4.5.1.2.1.

Dendritic spine reduction

4.5.1.2.2.

Neurotransmitter changes

4.5.1.3.

Vascular changes

4.5.2.

Cognitive Decline

4.5.2.1.

Memory impairment

4.5.2.1.1.

4.5.2.1.2.

Episodic memory

4.5.2.1.3.

Semantic memory

4.5.2.2.

Slowed processing speed

4.5.2.3.

Executive function changes

4.5.2.4.

Attention deficits

4.5.3.

Neuroinflammation

4.5.3.1.

Microglial activation

4.5.3.2.

Cytokine production

4.5.3.3.

Blood-brain barrier dysfunction

4.5.4.

Link to Neurodegenerative Diseases

4.5.4.1.

4.5.4.2.

Pathological mechanisms

4.5.4.3.

Protein aggregation

4.5.4.4.

Neuronal vulnerability

4.5.5.

4.5.5.1.

Sleep architecture alterations

4.5.5.2.

Circadian rhythm disruption

4.5.5.3.

Sleep disorders

4.6.

Integumentary System (Skin) Aging

4.6.1.

Intrinsic vs. Extrinsic Aging (Photoaging)

4.6.1.1.

Genetic factors

4.6.1.2.

UV exposure and environmental factors

4.6.1.2.1.

UVA and UVB damage

4.6.1.2.2.

Pollution effects

4.6.1.2.3.

4.6.2.

Wrinkling and Loss of Elasticity

4.6.2.1.

Collagen and elastin changes

4.6.2.1.1.

Collagen degradation

4.6.2.1.2.

Elastin fragmentation

4.6.2.2.

4.6.2.2.1.

Epidermal atrophy

4.6.2.2.2.

4.6.3.

Impaired Wound Healing

4.6.3.1.

Delayed repair processes

4.6.3.2.

Increased infection risk

4.6.3.3.

Angiogenesis defects

4.6.4.

Pigmentation Changes

4.6.4.1.

4.6.4.2.

Melanocyte dysfunction

4.6.5.

4.6.5.1.

4.6.5.2.

4.6.5.3.

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3. The Hallmarks of Aging: Molecular and Cellular Mechanisms

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5. Aging and Major Diseases