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On the “struggle between chemistry and biology during aging” – implications for DNA repair, apoptosis and proteolysis, and a novel route of intervention

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Abstract

The possible effects of specificspontaneous changes in protein chemistry onage-related homeostatic dysfunction arediscussed. Spontaneous racemization andisomerization of aspartic acid and deamidationof asparagine to four possible forms ofaspartic acid in caspases and their substratescould profoundly alter apoptotic activity.Deamidation of asparagine residues atcritically important sites of DNA glycosylasescould compromise base excision repairactivity. Furthermore, as oxidative damage mayenhance asparagine/aspartate instability inproteins, and erroneously-synthesized proteins show increased susceptibility tooxidative attack, it is beginning to appearthat the aberrant protein forms thataccumulate during ageing are possiblyinterrelated. The role of cell growth rates incontrolling constitutive proteolyticelimination of various forms of aberrantpolypeptides is then discussed. Finally, it ispointed out that three recently describedagents that delay senescence in cultured cells(aminoguanidine, N-t-butylhydroxylamine andkinetin) resemble carnosine in that they arealso likely to react with glycoxidisedproteins, as well as possess anti-oxidant activity. These observations suggest thatpluripotency may be a necessary pre-requisitefor effective anti-ageing activity.

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  1. Division of Biomolecular Sciences, Henriette-Raphael House, GKT School of Biomedical Sciences, King's College London, Guy's Campus, London Bridge, London, SE1 1UL, UK (email

    Alan R. Hipkiss

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Hipkiss, A.R. On the “struggle between chemistry and biology during aging” – implications for DNA repair, apoptosis and proteolysis, and a novel route of intervention. Biogerontology 2, 173–178 (2001). https://doi.org/10.1023/A:1011599321168

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