The Potential for Epigenetic Rejuvenation

Epigenetic change occurs with age, altering cellular behavior for the worse. Epigenetic reprogramming, via approaches derived from the use of Yamanaka factors to produce induced pluripotent stem cells, offers the potential to reset cell behavior in order to restore a more youthful tissue function. In mice, this is producing promising results. It remains an open question as to how age-related epigenetic change relates to fundamental causes of aging. It appears to be a far downstream consequence of underlying damage and dysfunction, but more recent work suggests that it may be an immediate consequence of stochastic DNA damage, and thus closer to root causes of aging than suspected. How distant epigenetic aging is from the causes of aging should set expectations regarding how effective and long-lasting epigenetic reprogramming will prove to be as a class of therapy.

Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks, including genetic and epigenetic alterations. These aging-associated epigenetic changes include DNA methylation, histone modification, chromatin remodeling, non-coding RNA (ncRNA) regulation, and RNA modification, all of which participate in the regulation of the aging process, and hence contribute to aging-related diseases. Therefore, understanding the epigenetic mechanisms in aging will provide new avenues to develop strategies to delay aging. Indeed, aging interventions based on manipulating epigenetic mechanisms have led to the alleviation of aging or the extension of the lifespan in animal models.

Small molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related conditions. In addition, adopting health-promoting activities, such as caloric restriction, exercise, and calibrating circadian rhythm, has been demonstrated to delay aging. Furthermore, various clinical trials for aging intervention are ongoing, providing more evidence of the safety and efficacy of these therapies.

Here, we review recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases. A better understanding of the critical roles of epigenetics in the aging process will lead to more clinical advances in the prevention of human aging and therapy of aging-related diseases.


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