PROJECT SUMMARY Shehzad Basaria, MD, an Associate Professor of Medicine and Endocrinology in the Division of Endocrinology, Diabetes, & Metabolism at Brigham and Women's Hospital, Harvard Medical School, submits this application for a K24 Mid-Career Development award to provide protected time to mentor trainees in Patient-Oriented Research (POR) in Endocrine aspects of Gero-Oncology. Dr. Basaria is one of the few endocrinologists worldwide specializing in endocrine and cardio-metabolic disorders in older men with cancer and androgen deficiency. He will pursue additional training to hone his mentoring skills in order to build on his established record of mentorship and foster the research careers of early investigators. Candidate: Dr. Basaria is a highly productive clinical researcher in the field of Endocrinology, Aging and Cancer. Since 2003, he has been continuously NIH-funded to investigate: i) endocrine and cardio-metabolic complications of androgen deprivation therapy (ADT) in men with prostate cancer (PCa), ii) benefits and risks of androgen replacement in older men, and iii) endocrinology of aging. He has conducted his investigations using NIH-supported infrastructure, including RO1s and R21 grants, data from the Baltimore Longitudinal Study of Aging (BLSA), the InChianti Study, and the Boston Pepper Center for Function-Promoting Therapies. With his uncommon skill set and strong POR program in Endocrinology and Gero-Oncology, he has been a sought-after collaborator and mentor at Brigham/Harvard and at national and international institutions. Mentoring Plan/Environment: This application will leverage the extensive training resources at Brigham/Harvard, including the Center for Clinical Investigation, the Brigham Research Institute for Clinical and Translational Research, and T32 training grants in a variety of specialties. It will also draw on the unparalleled resources of the Boston Pepper Center and other funded studies to serve as a platform for POR trainees at multiple levels. Research Plan: The novel research supported by this K24 award will make significant contributions to the 1A) The impact of ADT-induced profound hypogonadism and the resulting decline in muscle mass on physical function, 1B) The impact of ADT on fat infiltration of skeletal muscles and the association of this deterioration in muscle quality on physical function, and 2) The mechanisms by which testosterone replacement improves Cancer- Related Fatigue in older men with cancer. understanding of the impact of androgen deficiency in older men with cancer in three major areas: These novel aims will build on the ongoing work in Dr. Basaria's current R01s, explore new hypotheses, and expand opportunities for trainees.