Journal of internal medicine
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There is clear heritability of human longevity. However, the genetics of ageing is likely to be complex. Evolution theory tells us not to expect genes that have been selected to promote ageing. ⋯ In addition, there may be contributions either from late-acting deleterious genes that escape the force of natural selection or that trade benefit at an early age against harm at older ages. In some species, there is evidence that genes have evolved to detect and respond to changes in the environment, e.g. food supply. Evolutionary understanding can also help to understand important features of the human life history such as menopause.
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Ageing, or increased mortality with time, coupled with physiologic decline, is a nearly universal yet poorly understood biological phenomenon. Studies in model organisms suggest that two conserved pathways modulate longevity: DNA damage repair and Insulin/Igf1-like signalling. ⋯ Mice lacking SIRT6 develop a degenerative disorder that in some respects mimics models of accelerated ageing [Cell (2006) 124:315]. We discuss how sirtuins in general and SIRT6 specifically relate to other evolutionarily conserved pathways affecting ageing, and how SIRT6 might function to ensure organismal homeostasis and normal lifespan.