To adapt or not to adapt: Consequences of declining Adaptive Homeostasis and Proteostasis with age

Mechanisms of Ageing and Development
Laura C D PomattoKelvin J A Davies

Abstract

Many consequences of ageing can be broadly attributed to the inability to maintain homeostasis. Multiple markers of ageing have been identified, including loss of protein homeostasis, increased inflammation, and declining metabolism. Although much effort has been focused on characterization of the ageing phenotype, much less is understood about the underlying causes of ageing. To address this gap, we outline the age-associated consequences of dysregulation of 'Adaptive Homeostasis' and its proposed contributing role as an accelerator of the ageing phenotype. Adaptive Homeostasis is a phenomenon, shared across cells and tissues of both simple and complex organisms, that enables the transient plastic expansion or contraction of the homeostatic range to modulate stress-protective systems (such as the Proteasome, the Immunoproteasome, and the Lon protease) in response to varying internal and external environments. The age-related rise in the baseline of stress-protective systems and the inability to increase beyond a physiological ceiling is likely a contributor to the reduction and loss of Adaptive Homeostasis. We propose that dysregulation of Adaptive Homeostasis in the final third of lifespan is a significant factor in the agein...Continue Reading

Citations

Aug 23, 2019·Translational Psychiatry·Breno S DinizBrenda W J H Penninx
Feb 12, 2020·British Journal of Cancer·Ezio LaconiJames DeGregori
Jan 1, 2020·International Journal of Molecular Sciences·Tomasz BoczekLudmila Zylinska
Sep 1, 2020·Free Radical Biology & Medicine·Ethan L Ostrom, Tinna Traustadóttir
Mar 18, 2021·Antioxidants & Redox Signaling·Marilene DemasiLeonor Thomson
Apr 26, 2019·Redox Biology·Laura C D PomattoKelvin J A Davies

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