Research Projects

According to WHO, India has become the diabetic hub of the world with 74.2 million diabetic patients, and is likely to increase to 124.8 million in 2045. Diabetes and Obesity are emerging global health challenges aiding in the development of metabolic disorders associated with chronic low-grade inflammation. Adipose tissue being the major endocrine organ plays a crucial role in glucose, lipid, and energy homeostasis in response to changes in nutritional status, environment, lifestyle, and aging. Aging is the gradual process in which physical and mental capacity declines and the chances of diseases increased. Aging is correlated with increase in prevalence of diabetes, cardiovascular diseases and dyslipidemia. Adipose tissue senescence is now considered as one of the major culprit in obesity and age-associated metabolic disorders. The key unaddressed question in the research field is whether metabolic insult such as chronic hyperinsulinemia exposure in adipocyte/adipose tissue can exhibit accelerated senescence development and any immune metabolic level alterations are also associated with this phenomenon or not. Towards this, we wish to develop and characterize chronic hyper-insulinemia induced insulin resistance (IR) model in 3T3-L1 and hMSC derived adipocytes and their detailed effects on senescence pathways in in vivo tissue level too. Studies have shown that elevated glucose and lipid level causes inflammation and accumulation of senescent cell in adipose tissue. Due to its broad implications for general health and welfare in the ageing population, increasing healthy lifespan can be associated with a decrease in adipose senescence. We further intend to employ β3 adrenergic receptor agonists as potential senolytics as a strategy to eliminate senescent cells. These agonists were selected as they were increasing mitochondrial mass as well as exhibited improvement at mitochondrial fuctional aspects. Currently available therapies i.e. approved mirabegron and vibegron exhibit partial agonistic activity apart from β3 adrenergic i.e. β2 agonism therefore have implication in other cells like cardiovascular cells. Identification of novel and selective β-3 adrenergic receptor agonists would help to unravel the therapeutic potential as insulin sensitizer as well as senolytic to ameliorates senescence associated adipocyte dysfunction. This project will open new avenues for generating therapies for age-associated metabolic disorders.