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Elsevier, Mechanisms of Ageing and Development, 5-6(128), p. 355-364

DOI: 10.1016/j.mad.2007.03.004

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Analyses of human-chimpanzee orthologous gene pairs to explore evolutionary hypotheses of aging

Journal article published in 2007 by João Pedro de Magalhães ORCID, George M. Church
This paper is available in a repository.
This paper is available in a repository.

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Abstract

Compared to chimpanzees (Pan troglodytes), the onset of aging appears to be delayed in the human species. Herein, we studied human-chimpanzee orthologous gene pairs to investigate the selective forces acting on genes associated with aging in different model systems, which allowed us to explore evolutionary hypotheses of aging. Our results show that aging-associated genes tend to be under purifying selection and stronger-than-average functional constraints. We found little evidence of accelerated evolution in aging-associated genes in the hominid or human lineages, and pathways previously related to aging were largely conserved between humans and chimpanzees. In particular, genes associated with aging in non-mammalian model organisms and cellular systems appear to be under stronger functional constraints than those associated with aging in mammals. One gene that might have undergone rapid evolution in hominids is the Werner syndrome gene. Overall, our findings offer novel insights regarding the evolutionary forces acting on genes associated with aging in model systems. We propose that genes associated with aging in model organisms may be part of conserved pathways related to pleiotropic effects on aging that might not regulate species differences in aging.