Bcl-xL as a Modulator of Senescence and Aging.
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.
['Mas-Bargues|Cristina|C|0000-0003-1131-1894', 'Borrás|Consuelo|C|0000-0003-4606-1792', 'Viña|Jose|J|0000-0001-9709-0089']
D000375:Aging D000818:Animals D017209:Apoptosis D015415:Biomarkers D016922:Cellular Senescence D004249:DNA Damage D004198:Disease Susceptibility D005786:Gene Expression Regulation D006801:Humans D007157:Immunologic Surveillance D009928:Organ Specificity D011485:Protein Binding D015398:Signal Transduction D013312:Stress, Physiological D051020:bcl-X Protein
Bcl-xL senescence aging centenarians apoptosis senolytics immunosenescence