SIRT7: the seventh key to unlocking the mystery of aging

Abstract

Aging is a chronic yet natural physiological decline of the body. Throughout the life, humans are continuously exposed to a variety of exogenous and endogenous stresses, to which they engender various counteractive responses at the cellular, tissue, organ, as well as organismal levels. The compromised cellular and tissue functions, which occur due to genetic factors or prolonged stress (or even the stress response), may accelerate aging. Over the last two decades, the sirtuin (SIRT) family of lysine deacylases has emerged as a key regulator of longevity in a variety of organisms. SIRT7, the most recently identified member of SIRTs, maintains physiological homeostasis and provides protection against aging by functioning as a watchdog of genomic integrity, a dynamic sensor and modulator of stresses. SIRT7 decline disrupts metabolic homeostasis, accelerates aging and increases the risk of age-related pathologies including cardiovascular and neurodegenerative diseases, pulmonary and renal disorders, inflammatory diseases, and cancer etc. Here, we present SIRT7 as the seventh key to unlock the mystery of aging and its specific manipulation holds great potential to ensure healthiness and longevity.

Dysregulation of protein succinylation and disease development

“…It serves important functions such as stimulating the expression of ribosomal RNA, facilitating DNA damage repair, and balancing chromatin compaction (Lagunas-Rangel, 2023). These findings emphasize the critical role of SIRT7 in protecting chromatin structure, controlling innate immune regulation and ensuring reproductive protection during stem cell senescence (Raza et al, 2024).…”

SIRT7 Inhibits Melanin Synthesis of PIG1 and PIG3V by Suppressing the Succinylation of EZR

“…9 Recently, SIRT7 has been shown to function as a histone desuccinylase associated with chromatin compaction and genome stability, 10 in addition to regulating disease progression by participating in multiple cellular processes, like, SIRT7 has been found to selectively deacetylates histone H3 lysine 18 (H3K18Ac) in chromatin, which serves to maintain the cellular transformation ability of human cancer cells and tumor formation, 11 and play an important role in aging process. [12][13][14][15] The SIRT7 knockdown has been found to increase melanin production in melanoma cells, cementing its essential role in regulating melanin synthesis. 16 However, whether SIRT7 is involved in the pathogenesis of vitiligo remains unclear.…”

SIRT7 regulates NUCKS1 chromatin binding to elicit metabolic and inflammatory gene expression in senescence and liver aging

“…SIRT7 is one of the least characterized Sirtuins, however, one important aspect is its role in senescence and aging 9,10 . Deletion of SIRT7 in mice leads to progeria-like phenotypes with altered liver function 11,12 .…”