Ageing: Definition, Importance & Theories

Ageing Definition and Importance

• Ageing is defined as a decline in survival ability.
• Ageing impacts work capacity, increases disease risk, and drives significant healthcare costs.

Ageing Terminology

• Life expectancy: average age of death in a population.
• Lifespan: maximum attainable age for a species.

Features of Ageing

• Senescence: a natural decline in function
• Age-related diseases: illnesses linked to ageing.
• Senescent changes trigger and exacerbate age-related diseases.

Theories of Ageing

Wear and Tear Theory

• Free radicals: highly reactive atoms/molecules causing cellular damage.
• Glycation: reaction of sugars with proteins, leading to damage.
• Waste products: accumulate in cells, hindering function.
• Error-catastrophe: accumulation of errors in protein production harms cells.

Free Radicals in Ageing

• Free radical damage increases with age.

• Antioxidant defenses decrease with age.

• Free radicals are atoms/molecules with unpaired electrons.

• Free radicals damage DNA, RNA, proteins, enzymes, lipids, and cells.

• Sources of free radicals include phagocytic cells, radiation, smoking, and oxidation-reduction reactions.

• Types of Free Radicals: hydroxyl radical (OH), superoxide radical (O2), nitric oxide (NO).

• Antioxidants delay or impede oxidation, protecting against free radical damage.

• Extracellular antioxidants include vitamin E; intracellular antioxidants include superoxide dismutase (SOD) and catalase.

• SOD protects cells from superoxide damage.

Protein Glycation in Ageing

• Elderly populations are more susceptible due to glucose intolerance and diabetes.
• Glycation increases cross-linking, alters enzyme activity, affects immunogenicity, and changes protein half-lives/receptor recognition.

Accumulation of Waste Products

• Lipofuscin: lipid-rich pigment accumulating in cells, especially in long-lived tissues.
• Lipofuscin is produced via free radical peroxidation of cell membranes.
• The effects of lipofuscin accumulation are not fully understood.

Error-Catastrophe Theory

• Abnormal proteins form due to transcription/translation errors.
• Accumulation of abnormal proteins disrupts cellular function.
• Genome-based factors like programmed ageing and mutations contribute.

Genome-Based Ageing

• Programmed ageing: a genetically controlled process contributing to ageing.
• Mutations: DNA replication errors that accumulate, affecting cell viability.
• Hayflick Limit: cells divide a fixed number of times.
• Telomeres shorten with cell division, limiting division potential.
• Telomerase: enzyme that rebuilds telomeres.

Cellular Ageing

• Reduced mitochondrial function impairs energy production.
• Reduced DNA/RNA synthesis affects cellular processes.
• Reduced nutrient uptake impacts cellular function.
• Reduced chromosomal repair leads to DNA damage accumulation.
• Accumulation of waste products (like lipofuscin) disrupts cellular homeostasis.
• Changes in organelle shapes affect cellular integrity.

Ageing in Specific Systems

• Immune System: declines in antibody production, T cell function, and thymus size. Increased autoimmune reactions.
• Skin: wrinkles, pigmentation changes, hair loss, and impaired wound healing.
• Lungs: decreased size, elasticity, and capacity reducing gaseous exchange.
• Cardiovascular: stiffening of blood vessels, calcification, increased BP, and reduced cardiac output.
• Kidneys: decreased volume, reduced nephron function, and impaired waste elimination.
• Liver: reduced size and decreased function (e.g., drug detoxification).
• Muscles: atrophy and reduced work capacity.
• Endocrine System: decreased hormone production and receptor sensitivity.
• Brain: loss of weight, nerve cells, and increased amyloid deposition.
• Eyes: decreased lens flexibility, protein cross-linking.
• Body Composition: reduced muscle, increased fat.

Progeria

• Progeria (Hutchinson-Gilford syndrome): accelerated ageing.
• Extremely rare (1 in 10 million).
• Affected children age significantly faster.
• Average lifespan ~13 years.
• Common causes of death are heart disease and stroke.
• Diagnosis is challenging due to rarity.
• Management is focused on symptom relief and support.

Calorie Restriction and Ageing

• Calorie restriction extends lifespan and delays age-related diseases in numerous species.
• Calorie restriction may reduce age-associated mutations, free radical damage, and advanced glycation end products.

Anti-Ageing Therapy

• Companies are pursuing research to slow/reverse ageing.
• Companies researching anti-ageing therapies include Centagenetix, Elixir, Eurakon, Alteon, and Geron Corporation.
• Ongoing studies and therapies target specific mechanisms of ageing.