Acute kidney injury (AKI) and chronic kidney disease (CKD) are major contributors to overall morbidity andmortality in patients in the US. The overall objective of the proposed study is to establish untargeted andtargeted spatial metabolomics analysis of tissues from normal and diseased kidneys to assess cellularmetabolic states associated with healthy function, acute injury, chronic condition, and recovery.

Several clinically unrelated neurodegenerative disorders, termed conformational diseases, are character-ized by a common pathophysiology that involves aggregation and accumulation of misfolded proteins. All ofthese diseases activate cell stress signaling pathways, mainly the endoplasmic reticulum (ER) stress-inducedunfolded protein response (UPR) pathway. In particular, the proximal UPR kinase, PERK, is abnormally activein Alzheimer's disease (AD), Progressive Supranuclear Palsy (PSP) and Frontal Temporal Dementia (FTD)-affected brain regions.

Identification of small molecules that extend mouse lifespan provides new insights intomechanisms of longevity determination in mammals, and may lay the groundwork for eventualanti-aging therapies in humans. The NIA Interventions Testing Program (ITP) evaluates agentsproposed to extend mouse lifespan by retardation of aging or postponement of late lifediseases.

For the past three decades, the University of Texas Health Science Center at San Antonio (UTHSCSA) hashosted a premier Training Program in the biology of aging that has resulted in the development of a newgeneration of leaders in this field. This application seeks to continue this T32 Training Program and we requestfunds to support four predoctoral and four postdoctoral trainees.