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Review
. 2021 Mar:194:111418.
doi: 10.1016/j.mad.2020.111418. Epub 2020 Dec 16.

Decline in biological resilience as key manifestation of aging: Potential mechanisms and role in health and longevity

Svetlana Ukraintseva  1 , Konstantin Arbeev  2 , Matt Duan  3 , Igor Akushevich  4 , Alexander Kulminski  5 , Eric Stallard  6 , Anatoliy Yashin  7
Affiliations
Review

Decline in biological resilience as key manifestation of aging: Potential mechanisms and role in health and longevity

Svetlana Ukraintseva et al. Mech Ageing Dev. 2021 Mar.

Abstract

Decline in biological resilience (ability to recover) is a key manifestation of aging that contributes to increase in vulnerability to death with age eventually limiting longevity even in people without major chronic diseases. Understanding the mechanisms of this decline is essential for developing efficient anti-aging and pro-longevity interventions. In this paper we discuss: a) mechanisms of the decline in resilience with age, and aging components that contribute to this decline, including depletion of body reserves, imperfect repair mechanisms, and slowdown of physiological processes and responses with age; b) anti-aging interventions that may improve resilience or attenuate its decline; c) biomarkers of resilience available in human and experimental studies; and d) genetic factors that could influence resilience. There are open questions about optimal anti-aging interventions that would oppose the decline in resilience along with extending longevity limits. However, the area develops quickly, and prospects are exciting.

Keywords: Aging; Anti-aging interventions; Biomarkers; Cell repair; Debris accumulation; Genetics of resilience; Longevity; Reserve depletion; Resilience; Robustness; Slowdown.

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Figures

Figure 1.
Figure 1.
Resilience (ability to recover) vs. robustness (ability to resist deviation and avoid damage). Explanation in text.
Figure 2.
Figure 2.. Relationships between aging, decline in biological resilience, and longevity.
Major aging components (depletion of limited body reserves; slowdown of physiological processes and responses, and imperfect mechanisms of repair and cleaning) together contribute to the decline in the resilience (ability to recover), which in turn contributes to the increase in vulnerability to death with age, eventually limiting longevity even in people without major chronic diseases. Prospective anti-aging interventions (examples on the top) coming from experimental studies already target these aging components (see in text). For more optimal results, such interventions may need to act together, to simultaneously (i) replenish stem and other cells, (ii) improve quality of cell repair, (iii) enhance removal of senescent and malfunctioning cells, metabolic waste, and debris from tissues, (iv) decelerate the decline in speeds of metabolic, proliferative and signal processing responses to stressors, so that this decline (shown as “slowdown” on the figure) would progress slower with age.
Figure 3.
Figure 3.
Enrichment with GO processes in the set of 490 aging and longevity-related genes from GenAge and LongevityMap bases (Tacutu, Thornton et al. 2018). The results show that these genes are commonly involved in cell responses to stress, proliferation and apoptosis (the results obtained with MetaCore software from Clarivate Analytics).
Figure 4.
Figure 4.
Simplified picture of the aging-related signaling pathways that have been in major focus of experimental aging research: IGF-1/AKT/FOXO3 - mediated growth/survival, TP53/P21/P16 - mediated apoptosis/senescence/autophagy, and mTOR/S6K - mediated autophagy/survival/growth. These pathways biologically interact and together decide on specific outcomes of cell responses to stress/damage, such as apoptosis, senescence, survival, growth, division, or autophagy. The choice of a particular outcome in given conditions may differ between carriers of different genotypes, which might contribute to the differences in pace of aging between individuals, species or strains (Image by Ukraintseva© 2020, using MetaCore Pathway Map Creator tool from Clarivate Analytics).
See this image and copyright information in PMC

References

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