Aging

Aging is the progressive decline in physiological function over time that increases vulnerability to disease and death. It is a nearly universal feature of multicellular life (with a few notable exceptions among some animals and plants).

Core biological mechanisms

Aging is driven by several interconnected processes, often summarized as the “hallmarks of aging”:

• Genomic instability — accumulation of DNA damage and mutations.
• Telomere attrition — progressive shortening of chromosome ends.
• Epigenetic alterations — changes in DNA methylation, histone modifications, and chromatin structure that disrupt gene regulation.
• Loss of proteostasis — impaired protein folding, degradation, and clearance (leading to aggregates).
• Disabled macroautophagy — reduced cellular recycling of damaged components.
• Deregulated nutrient sensing — especially involving pathways like insulin/IGF-1, mTOR, AMPK, and sirtuins.
• Mitochondrial dysfunction — declining energy production and increased reactive oxygen species.
• Cellular senescence — permanent cell-cycle arrest accompanied by a pro-inflammatory secretory phenotype (SASP).
• Stem-cell exhaustion — reduced regenerative capacity.
• Altered intercellular communication — chronic low-grade inflammation (“inflammaging”) and other signaling disruptions.
• Dysbiosis — changes in the microbiome.
• Extracellular matrix stiffening and other tissue-level changes.

These processes interact; intervening in one often affects others.

Why we age (evolutionary perspective)

Natural selection weakens with age because fewer individuals survive to older ages to reproduce. Genes that are beneficial early in life can have harmful effects later (antagonistic pleiotropy). There is no strong evolutionary pressure to maintain the body indefinitely after reproductive years.

Measurable aspects and variability

• Chronological age vs. biological age (the latter can be estimated via epigenetic clocks, such as those based on DNA methylation patterns, or composite biomarkers).
• Large individual differences exist due to genetics, lifestyle, environment, and chance. Some people remain robust into their 90s or beyond; others show accelerated decline.
• Maximum human lifespan has remained roughly stable (around 115–120 years for verified cases), while average life expectancy has risen dramatically through public health, medicine, and reduced early-life mortality.

Interventions and research directions

Lifestyle factors with the strongest evidence for slowing aspects of biological aging or extending healthspan include:

• Caloric restriction or intermittent fasting (in many model organisms; human data more limited but promising for metabolic health).
• Regular physical activity (especially resistance + aerobic training).
• Avoidance of smoking, excessive alcohol, and severe obesity.
• Adequate sleep and management of chronic stress.

Pharmacological and experimental approaches under active investigation include senolytics (drugs that clear senescent cells), mTOR inhibitors (e.g., rapamycin analogs), NAD+ boosters, metformin, and various gene- or cell-based therapies. Many show robust effects in mice and other models; translation to healthy humans is ongoing and results are mixed or preliminary.