In weight gain, increased adiposity is accompanied by accelerated aging of fat tissue. This change is most marked in visceral adipose, where it cultivates a specific array of inflammatory changes that enable these fat cells to survive under the disadvantageous conditions. With the expansion of fat tissue, this pattern of altered cytokine production is known as a “senescence-associated secretory phenotype,” or SASP. In adipose, having a SASP affects immune homeostasis and energy metabolism, with long-term health consequences. A number of plant nutrients have long been studied for their effects on biological aging, and an emerging priority is the identification of natural and synthetic senolytic agents, which aid the elimination of overly-aged and damaged cells. The dietary flavonoid quercetin, for example, is known to target senescent cells within the endothelium of blood vessels. By aiding clearance of poorly functioning cells, senolytics have the potential to allow organs, in turn, to regain healthier function. In previous studies, the researchers discovered that senescent cells depend on survival-oriented metabolic networks to avoid normal programmed cell death. In this experiment, mice with either high-fat diet-induced obesity or genetic predisposition to obesity were given a combination of two senolytic substances: quercetin and the drug dasatinib. During multiple courses of administration of these senolytics, animals were examined for functional and structural changes in vital organs, the abundance of senescent cells within adipose tissue, and alterations in animals’ senescence-associated secretory phenotype (SASP).
Quercetin Helps Target Pathways of Cell Aging and Survival
KEY TAKEAWAY: In fat tissue, increased senescent cell burden appears to drive insulin resistance by cultivating a senescence-associated secretory phenotype (SASP) and encouraging immune infiltration of tissues, especially in metabolically sensitive visceral adipose. This innovative study highlights quercetin as a nutritional means of improving normal elimination of aged or damaged cells—an action that may also benefit healthy organ function.
