Longevity theories

Aging is the progressive loss of physiological integrity (the normal structure and working of the body) that leads to impaired function and greater vulnerability to death, and it is the main risk factor for cancer, diabetes, cardiovascular disease and neurodegenerative disease [1]. Research on the biology of aging looks for the underlying processes that drive this decline. Studies of Danish twins born between 1870 and 1900 estimated the heritability of lifespan (the share of differences in lifespan explained by genes) at 0.26 in men and 0.23 in women [2], and an analysis of family trees covering hundreds of millions of people, which accounted for spouses resembling each other, put it well below 10% [3]. Most variation in lifespan is therefore attributed to factors other than inherited genes. The inherited risk of specific diseases, which family history captures more strongly than it captures lifespan, is described in Family history and genetics.

The most widely cited framework for these processes is the hallmarks of aging. The 2013 version named nine: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence (cells that permanently stop dividing but stay in the tissue), stem cell exhaustion and altered intercellular communication [1]. The 2023 update added disabled macroautophagy (the cell recycling its own worn-out parts), chronic inflammation and dysbiosis (an imbalance in gut microbes), for twelve in total, and defined a hallmark as a process that appears with age, accelerates aging when experimentally intensified, and slows aging when treated [4]. The hallmarks are interconnected rather than independent [4].

This section covers two of the hallmarks in depth. Telomeres describes the protective DNA caps on chromosome ends, which shorten as cells divide and set a limit on cell division; in pooled data on 121,749 people, the shortest quarter of telomere length was associated with a 26% higher death rate than the longest quarter [5]. Inflammation and aging describes the chronic, low-grade inflammation that rises with age and the trials testing whether blocking it prevents disease, including CANTOS, in which the antibody canakinumab lowered cardiovascular events (such as heart attacks and strokes) in 10,061 heart attack survivors [6]. Inflammatory markers are also associated with poor sleep, and regular exercise has anti-inflammatory effects, topics covered in how sleep works and exercise and longevity [7, 8].