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New approaches to bring back youthfulness to aged stem cells
Aging is a nearly universal process affecting all tissues. Despite its constancy in our lives, aging remains mysterious at a fundamental level. Nevertheless, common hallmarks of aging across different species have been proposed offering an integrated view of the basic mechanisms of aging. Primary hallmarks include cell autonomous changes linked to epigenetic alterations, genomic instability, telomere attrition and loss of proteostasis (protein homeostasis), which are followed by antagonistic responses such us deregulated nutrient sensing, altered mitochondrial function and cellular senescence. Aging hallmarks converge in the exhaustion of stem cells, which provokes tissue regenerative decline. Skeletal muscle provides a stark example of this decline. Its stem cells sustain muscle regeneration throughout life but at advanced age they fail for largely undefined reasons. Several causes for this age-associated stem cell regenerative failure are emerging: decline in proteostatic quality-control mechanisms, metabolic alterations, entry into senescence and changes in the systemic (circulatory) environment. I will review our recent findings on how to improve the regenerative capacity of old stem cells by countering these age-associated alterations, with the ulterior idea that the aging process is malleable and that it is feasible to rejuvenate aged cells and tissues.