From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).

摘要

Aging is accompanied by a gradual loss of cellular function and systemic weakening of the homeostasis of multiple tissues, leading to a variety of age‑related diseases and eventual mortality. Super‑enhancers are a distinct class of cis‑regulatory elements with strong transcriptional activation properties; they are bound by a large number of key transcription factors and cofactors, and possess distinct characteristic modification marks of enhancers. The past decade has seen an exponential growth in the field of super‑enhancer research, partly because of the strong transcriptional activity of super‑enhancers. Super‑enhancers are notably activated in response to aging or aging‑related factors, and serve a pivotal role in aging and aging‑related diseases by modulating key biological processes, including cell proliferation, differentiation and senescence. In the present review, the changes in super‑enhancers under aging‑related stimuli are initially discussed. The mechanistic contributions of super‑enhancers to cellular senescence from the perspective of DNA damage and mitochondrial dysfunction, two hallmarks of aging, are then systematically summarized. Furthermore, the pathogenic involvement of super‑enhancer dysregulation in specific age‑related disorders, including atherosclerosis and type Ⅱ diabetes, is explored, highlighting the potential of super‑enhancers as therapeutic targets. Finally, the current challenges and prospects of super‑enhancers within the context of aging biology are discussed, aiming to provide novel theoretical guidance for the treatment of age‑associated diseases.