Error-protein metabolism and ageing

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How errors in protein synthesis may play a role in aging appears to be reviewed.

I liked the paragraph:

“Dietary limitation of methionine in rats and mice induced anti-ageing effects at whole animal and cellular levels, including suppression of deleterious changes to mitochondria, similar to, but not so extensive as, those induced by caloric restriction (Ayala et al. 2007; et al. 2005; Naudi et al. 2007; Sanz et al. 2006; Richie et al. 1994). Changes in error-protein generation can explain this phenomenon, however, methionine is the initiating amino acid in protein synthesis in cytosol and mitochondria. Consequently, methionine-limitation would lower translation initiation frequency and decrease synthesis of normal and erroneous polypeptides.”

The below paper is pdf-availed

Hipkiss AR.Error-protein metabolism and ageing.Biogerontology. 2008 Oct 16. [Epub ahead of print]PMID: 18923917

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.

Keywords Error-proteins - Mitochondria - Proteases - Aging - Ribosomes - Mis-translation - Chaperone proteins - Proteasomes - Proteolysis

-- Al Pater, alpater@...