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Error-protein metabolism and ageing

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Abstract

Ageing and many associated pathologies are accompanied by accumulation of altered proteins. It is suggested that erroneous polypeptide biosynthesis, cytosolic and mitochondrial, is not an insignificant source of aberrant protein in growing and non-mitotic cells. It is proposed that (i) synthesis of sufficient proteases and chaperone proteins necessary for rapid elimination of altered proteins, from cytoplasmic and mitochondrial compartments, is related to cellular protein biosynthetic potential, and (ii) cells growing slowly, or not at all, automatically generate lower levels of protease/chaperone molecules than cells growing rapidly, due to decreased general rate of protein synthesis and lowered amount of error-protein produced per cell. Hence the increased vulnerability of mature organisms may be explained, at least in part, by the decline in constitutive protease/chaperone protein biosynthesis. Upregulation of mitochondria biogenesis, induced by dietary restriction or aerobic exercise, may also increase protease/chaperone protein synthesis, which would improve cellular ability to degrade both error-proteins and proteins damaged post-synthetically by reactive oxygen species etc. These proposals may help explain, in part, the latency of those age-related pathologies where altered proteins accumulate only late in life, and the beneficial effects of aerobic exercise and dietary restriction.

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  1. Centre for Translational Medicine and Therapeutics, William Harvey Research Institute, Bart’s and the London Queen Mary’s School of Medicine and Dentistry, Charterhouse Square, London, EC1 6BQ, UK

    Alan R. Hipkiss

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Hipkiss, A.R. Error-protein metabolism and ageing. Biogerontology 10, 523–529 (2009). https://doi.org/10.1007/s10522-008-9188-9

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