Senescence and DNA Damage in Adipocytes and Fat Tissues and Its Potential Amelioration through Nutritional Interventions

Abstract

Accumulating evidence demonstrates that senescence and the associated inflammatory phenotype (SASP) also occur in post-mitotic cells such as mature adipocytes. Visceral adipose tissue in humans is susceptible to inflammation due to nutritional imbalance and ageing. However, while adipose tissue has been well researched in the context of obesity, senescence of differentiated adipocytes has not been investigated thoroughly. Our group recently demonstrated that ageing and normal ad libitum (AL) nutrition in mice resulted in increased adipocyte size, DNA damage, p16INK4a expression and inflammation in visceral adipose tissue while some of these senescence markers could be alleviated by dietary restriction (DR). Moreover, another dietary restriction study described a “metabolic memory” as protection against AL-induced senescence after shifting mice from DR back to AL nutrition. Other recent DR studies on mice of different ages analysed the transcriptional profile of adipose tissue and described a metabolic memory for AL at high age. Finally, our group modelled nutritional imbalance in vitro through treatment of primary human subcutaneous and omental adipocytes with the saturated fatty acid (FA) palmitic acid (PA). This resulted in a significant increase in DNA damage as well as p16INK4a levels correlating with enhanced intracellular lipid accumulation. In contrast, DNA damage could be prevented with the unsaturated FA oleic acid (OA). With olive oil being an important part of the Mediterranean diet another study found also other oils such as argan oil to have similar effects of preventing DNA damage in vivo and in vitro. This review is focused on senescence, DNA damage and inflammation in WAT and adipocytes including nutritional interventions in vivo and in vitro. It also gives some basic background on these topics. However, it is not a systematic review but aims to highlight recent developments and nutritional interventions in the areas of senescence and DNA damage related to adipocyte tissues and cells.