![]() ![]() ![]() Reprogramming with Yamanaka factors resets epigenetic clocks to zero. Epigenetic clocks tick throughout the entire human lifespan, starting at conception, and they tick in normal human cells in vitro, but not in embryonic or pluripotent cells. Epigenetic clocks can also predict mortality risk in humans, and universal mammalian epigenetic clocks can predict the age of individuals from mammalian species with vastly different lifespans. In recent years, the development of epigenetic clocks has shown that a relatively small number of methylation sites, some becoming hypermethylated and others becoming hypomethylated with age, can predict human chronological age with surprisingly high accuracy. Despite these advances, why human beings age remains a mystery subject to intense debate. There has also been considerable progress in manipulating ageing in model organisms using genetic, dietary, and pharmacological interventions. By contrast, programmatic theories argue that ageing results from predetermined mechanisms encoded in the genome, rather than stochastic damage accumulation. ![]() Although damage can be broadly defined as any change that affects function, here I refer more specifically to molecular damage hypothesized to drive ageing, such as by-products of metabolism, unwanted chemical modifications, and other types of molecular damage affecting crucial cellular components like the genome, telomeres, mitochondria, and proteins. Most damage-based theories postulate that inefficient repair mechanisms result in singular or multiple, and often interacting, forms of damage accumulation. Many theories of why we age have been proposed, including damaged-based and programmatic theories, with the former currently more widely accepted and studied. Although ageing is integral to human biology and has a major impact on society and medicine, it remains at the mechanistic level a poorly understood process. ![]() The human ageing process entails countless changes at multiple biological levels, degenerative changes in virtually all organs and body systems, and increased susceptibility to several diseases, such as cardiovascular diseases, cancer, neurodegenerative diseases, type II diabetes, and many infectious diseases. Ageing can be defined as an inevitable and progressive deterioration of physiological function, accompanied by an increase in vulnerability and mortality with age. ![]()
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