Cellular senescence and its role in white adipose tissue

• Cell senescence is defined as a state of irreversible cell cycle arrest combined with DNA damage and the induction of a senescence-associated secretory phenotype (SASP). This includes increased secretion of many inflammatory agents, proteases, miRNA's, and others. Cell senescence has been widely studied in oncogenesis and has generally been considered to be protective, due to cell cycle arrest and the inhibition of proliferation. Cell senescence is also associated with ageing and extensive experimental data support its role in generating the ageing-associated phenotype. Senescent cells can also influence proximal "healthy" cells through SASPs and, e.g., inhibit normal development of progenitor/stem cells, thereby preventing tissue replacement of dying cells and reducing organ functions. Recent evidence demonstrates that SASPs may also play important roles in several chronic diseases including diabetes and cardiovascular disease. White adipose tissue (WAT) cells are highly susceptible to becoming senescent both with ageing but also with obesity and type 2 diabetes, independently of chronological age. WAT senescence is associated with inappropriate expansion (hypertrophy) of adipocytes, insulin resistance, and dyslipidemia. Major efforts have been made to identify approaches to delete senescent cells including the use of "senolytic" compounds. The most established senolytic treatment to date is the combination of dasatinib, an antagonist of the SRC family of kinases, and the antioxidant quercetin. This combination reduces cell senescence and improves chronic disorders in experimental animal models. Although only small and short-term studies have been performed in man, no severe adverse effects have been reported. Hopefully, these or other senolytic agents may provide novel ways to prevent and treat different chronic diseases in man. Here we review the current knowledge on cellular senescence in both murine and human studies. We also discuss the pathophysiological role of this process and the potential therapeutic relevance of targeting senescence selectively in WAT.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Näringslära (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Nutrition and Dietetics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

DNA-damage

premature senescence

secretory phenotype

life-span

growth

cells

p53

dysfunction

regulator

gene

Endocrinology & Metabolism

Nutrition & Dietetics

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