3128 – THE RETIREMENT STRESS INCREASES BIOLOGICAL AGE: SEARCHING STRESS-INDUCED INFLAMMATORY AND IMMUNOSENESCENCE FACTORS OF BIOLOGICAL AGING ACCELERATION.

As the retirement age increase in many countries, new approaches for active healthspan prolongation in a period before and after retirement is required. The age-related elevation of immunosenescence and inflammation increase predisposition to neurodegenerative (NDD), cardiovascular disorders (CVD), cancer and risk of virus-induced mortality. Modern life requires hard work even in pre-retirement age and is often accompanied by stress. Chronic stress-induced cortisol release suppresses lymphocytes and granulocytes sensitivity to activation signals. We show that pre-retirement stress is correlated with an increase of biological age indicators (BAI) (Berezina et al., 2020). Also, ageing is characterised by the rise of CD57++ immunosenescent lymphocytes number, like their increase during the stress and inflammation. Combination of chronic inflammation, high ratio of senescent immune cells and chronic stress is unfavourable background for NDD, CVD and proliferative malignancies development. We consider testing of inflammatory factors, cortisol level and senescent blood cells by multicolour FACS analysis to introduce multiparametric model for age-related disorders predisposition assessment. Analysis of patient's PBMCs ex vivo for phagocytosis, cytokine secretion, lymphoid cells proliferation ability is used as a test for screening of natural or synthetic compounds and FDA approved drugs. This approach will suggest candidate drugs for early prevention of immune senescence, age and stress-related diseases. We hope that combination of psychological assistance, anti-inflammatory treatment (NFkB/mTOR/Akt inhibition, AMPK/SIRT pathway activation) and cortisol control will help to reduce unspecific inflammation, to overcome immunosenescence, to increase virus resistance, and will be beneficial for prolongation of healthspan. Funding: The Russian Science Foundation N 191800058.