Declining Resilience as a Manifestation of Aging

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Resilience, meaning the ability to recover from wounds, infection, and other forms of damage, is more or less the flip side of frailty in aging. Frailty increases, resilience decreases. A damaged system is less robustly resilient to further damage, as reliability theory tells us. Degenerative aging is precisely an accumulation of cell and tissue damage at the molecular level, followed by all the myriad downstream dysfunctions and breakages caused by that damage. When we approach the treatment of aging, the guiding principle should be a focus on root cause damage and repair of that damage.

Decline in biological resilience (ability to bounce back and recover) is a key manifestation of aging that contributes to increase in vulnerability to death with age, limiting longevity even in people without major diseases. Resilience is different from robustness which refers to the ability to avoid damage and its destructive consequences whatsoever. The robustness generally declines during aging; however, it may improve in some health domains, sometimes at the cost of resilience to future adverse events.

We propose that aging can be viewed as a combination of three universal components: (i) depletion of limited body reserves (e.g., of stem cells, immune cells, muscle cells, neural cells, etc.), which poses limits to recovery; (ii) slowdown of physiological processes and responses to stress/damage, which delays the recovery with age; and (iii) inherently imperfect mechanisms of cell/tissue repair and cleaning, which result in incomplete recovery and damage accumulation over time. These aging components together create the age-decline in resilience, which in turn contributes to increase in mortality risk with age eventually limiting longevity even in people without major diseases.

These aging components can be seen in all aging animals, albeit their relative contributions to the decline in resilience, as well as to longevity limits, may differ across species, which could contribute to the variability of longevity and pace of aging among the species and strains. This may also be a reason why the effects of anti-aging interventions observed in lab animals are not always replicated in humans. There are open questions about relative impacts of the different aging components on the decline in resilience and the increase in mortality risk with age. However, the area develops quickly, and prospects are encouraging.

Finding the 'optimal' anti-aging intervention that could oppose the decline in resilience and also extend the species longevity limits remains a challenging problem. To be more efficient, the anti-aging interventions may need to target several aging components at once, e.g., help replenish body reserves, enhance cell repair and tissue cleaning, and attenuate the slowdown of metabolism, proliferation, and information processing, simultaneously.

Link: https://doi.org/10.1016/j.mad.2020.111418

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source https://www.fightaging.org/archives/2021/01/declining-resilience-as-a-manifestation-of-aging/