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The Hallmarks of Aging

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Published Article
DOI: 10.1016/j.cell.2013.05.039
  • Biochemistry
  • Genetics And Molecular Biology(All)


Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations , loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Introduction Aging, which we broadly define as the time-dependent functional decline that affects most living organisms, has attracted curiosity and excited imagination throughout the history of humankind. However, it has only been 30 years since a new era in aging research was inaugurated following the isolation of the first long-lived strains in Caenorhabditis elegans (C. elegans) (Klass, 1983). Nowadays, aging is subjected to scientific scrutiny based on the ever-expanding knowledge of the molecular and cellular bases of life and disease. The current situation of aging research exhibits many parallels with that of cancer research in previous decades. The cancer field gained major momentum in 2000, with the publication of a landmark paper that enumerated six hallmarks of cancer (Hanahan and Weinberg, 2000), recently expanded to ten (Hanahan and Weinberg, 2011). This categori-zation has helped to conceptualize the essence of cancer and its underlying mechanisms. At first sight, cancer and aging may seem to be opposite processes: cancer is the consequence of an aberrant gain of cellular fitness, whereas aging is characterized by a loss of fitness. At a deeper level, however, cancer and aging share common origins. The time-dependent accumulation of cellular damage is widely considered to be the general cause of aging (Gems

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