SENS5 Video: Increased Damage to Proteins in Aging

At its simplest, aging is nothing more than damage and the flailing of adaptive systems that try and fail to cope with operating while damaged. The damage of aging comes in a variety of forms, but much of it involves broken proteins. Proteins are the cogs and wheels of cellular machinery, intricate assemblies of atoms encoded in your DNA and tailored by evolution to specific roles. The inside of any cell is a madhouse of flowing material and chemical reactions, however, not all of them benign. There is constant turnover as proteins are damaged, recycled, and replaced, some more often than others. In this dynamic environment of wear and repair, it takes decades for forms of damage to begin to overwhelm the recycling machinery, but the downward slide only gets faster with time.

Here is a recently posted video from last year's SENS5 conference that looks at research into this contribution to degenerative aging:

Proteins undergo continual spontaneous modifications in physiological systems leading to change in their structure and function. This increases with age. ... Data of protein damage is now being combined to produce refined dynamic, multi-compartmental mathematical models of in-life protein damage. Accumulation of protein damage in ageing, that is, increased steady-state levels of damaged proteins occurs as a consequence of: (i) increased rates of protein damage -- linked to increased rate of damaging agent formation and decreased anti-glycation and oxidant defences, (ii) decreased rates of repair of damaged proteins, and (iii) decreased rates of proteolysis of damaged proteins.

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Antistress gene transcriptional responses also decline with age leaving the proteome particularly vulnerable in periods of oxidative, metabolic and lipogenic stress. Healthy ageing has been achieved in transgenic animals through manipulation of oxidative and non-oxidative mechanisms. Healthy ageing may be available for people through dietary supplements which prevent decline in expression in adulthood of a battery of genes protective against multi-modal stresses. Such interventions are designed to maintain vascular, metabolic, skeleto-muscular and other aspects of health, in part, through preventing increased flux of damage to proteins and increased steady-state levels of damaged proteins.

There are a fair number of researchers interested in protein homeostasis in this way - that is the maintenance of relative protein abundances and low damage levels over time. Aging manifests as an accelerating disruption of homeostasis, and the thinking is that there may be something to be learned from the details of how this disruption proceeds.

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