The PHenotypes of Aging and SEnescence (PHASE) study will develop a panel of markers in plasma that reflect cell senescence. Senescence is a fundamental process of biological aging whereby cells irreversibly stop dividing senescent cells. They secrete products, the Senescence-Associated Secretory Phenotype (SASP) and play a pivotal role in age-related diseases and survival. The partial elimination of senescent cells by senolytic treatments reverses age-related dysfunction and increases mean lifespan in mice. Treatments that reduce senescent cells are now being tested in clinical trials so there is an urgent need for a panel of markers of senescence to test and compare the efficacy of candidate treatments and identify individuals who, because of a high burden of senescence, are most likely to benefit from such treatment. PHASE will follow a decision tree with four phases to systematically identify, select, optimize, and clinically validate panels of circulating markers of cell senescence. In the first phase we will assemble a comprehensive panel of candidate markers from extensive research on senescence by our team and others? research. In the second phase we will select a provisional research panel of SASP markers for studies of clinical endpoints based on evidence that the marker reflects underlying cell senescence because it increases with aging, is correlated with senescent cell burden in several tissues, and is reduced by senolytic treatments. In the third phase we will test and optimize the assays. In the fourth phase we will test the associations between the markers and several clinical outcomes, such as osteoarthritis and cardiovascular disease using plasma and data from the Health ABC cohort study. We will also test the association between the markers and healthspan ? survival free of disability and dementia, and reaching over age 100 years. PHASE will provide a panel of markers reflecting cell senescence that can be widely used in clinical research, clinical trials and clinical practice to target treatments that could slow the process of aging, reduce the risk of many disabling and fatal aging-related conditions, and increase healthspan.

Public Health Relevance

The PHenotypes of Aging and SEnescence (PHASE) study will develop a panel of markers for the process of cell senescence, a fundamental biological process of aging in which cells stop dividing and begin to secrete products that impair the function of other cells and tissues. Treatments that partly eliminate senescent cells, ?senolytics,? reduce effects of aging and prolong life in mice and are now being tested in humans. PHASE will produce markers that can be used to test the efficacy of new treatments in humans and identify people who are most likely to benefit from senolytic therapy.

National Institute of Health (NIH)
National Institute on Aging (NIA)
High Priority, Short Term Project Award (R56)
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Special Emphasis Panel (ZAG1)
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Rossi, Winifred K
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California Pacific Medical Center Research Institute
San Francisco
United States
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