Does hereditary metabolic disease modulate senescence and ageing?

• Published in: Journal of inherited metabolic disease 2002-05, Vol.25 (3), p.235-251
• Main Author: Scriver, C. R.
• Format: Article
• Language: English
• Subjects: Aging; Biological Evolution; Humans; Life Expectancy; Metabolism, Inborn Errors - physiopathology; Mutation
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1023/A:1015650517020

Hereditary metabolic diseases in the context of evolutionary biology elicit interesting questions about ageing and senescence: Will persons successfully treated for inborn errors of metabolism, age and die prematurely because of compromised longevity? Because some unhealthy longevity has its origins in germline and somatic mutational processes, and in an inability to withstand metabolic stress, are there lessons to be learned about senescence from hereditary metabolic disease? Why are ageing, senescence and death necessary for Homo sapiens and how do they happen? These questions form the theme upon which several variations are played during the course of this essay. The theory of the disposable soma recognizes genomic and environmental events, well‐seasoned by Chance, as determinants of ageing and senescence. Together, they cause the somatic damage that results in death. Genomics will reveal genes involved in longevity, both healthy and unhealthy. There will be schedules of gene expression behind our life‐history traits. As in the field of hereditary metabolic disease, analogous genetic enquiries about ageing can be formulated. For example, how will heterozygotes age? Will association studies in centenarians reveal ‘longevity genes’? Will disparate longevity in sib pairs reveal genetic factors? If there are ‘ageing’ mutations, of what types and with what effects? Will these initiatives lead to healthier longevity? A deeper question yet remains: why has human biology invested so greatly in grandparenthood?