Abstract
Many features of aging result from the incapacity of cells to adapt to stress conditions. When cells are overwhelmed by stress, they can undergo senescence to avoid unrestricted growth of damaged cells. Recent findings have proven that cellular senescence is more than that. A specific grade of senescence promotes embryo development, tissue remodeling and wound healing. However, constant stresses and a weakening immune system can lead to senescence chronicity with aging. The accumulation of senescent cells is directly related to tissue dysfunction and age-related pathologies. Centenarians, the most aged individuals, should accumulate senescent cells and suffer from their deleterious effects, however, they enjoy a compression of morbidity. We have shown that they overexpress B-cell lymphoma-extra large (Bcl-xL). Bcl-xL could avoid an excessive burden of senescent cells through the regulation of intrinsic apoptosis, mitochondrial bioenergetics and oxidative stress. On the other hand, Bcl-xL maintains a fully functional immune system that ensures an efficient clearance of senescent cells. Moreover, there is a paradox, as inhibitors of Bcl-xL have been employed as senolytic agents, which have been shown to protect from aging in animal models. In this review, we aim to discuss how Bcl-xL could modulate senescence-associated harmful effects in centenarians, protecting them from the burden of accumulation of senescent cells.
Highlights
These results suggest that overexpression of B-cell lymphoma-extra large (Bcl-xL) is able to rescue impaired lymphocytes from septuagenarians to behave like those from centenarians and young individuals
Senescence is a physiological response with a particular role from embryonic development until adulthood
Chronic senescence appears upon aging as a result of the accumulation of senescent cells as a consequence of constant damage through life and an impaired clearance by the immune system
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Both mitotic and postmitotic cells will undergo one of the three main pathways that will determine the pro-death or pro-survival fate of a single cell towards the benefit of the whole organism [4]. These pathways are autophagy, apoptosis and senescence. It is known that autophagy is downregulated through aging [5] and this reduced function has been blamed for the accumulation of damaged proteins in old organisms [6,7], but it has been reported that it contributes to cell survival and to cell death as well [8]. What determines that a cell decides one pathway, or another is yet to be clarified
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