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.

Alzheimer's disease (AD) is the most common neurodegenerative disease affecting millions of Americans.Neurons have a large amount of polyunsaturated fatty acids in membrane phospholipids that are vulnerable toattack by reactive oxygen species to result in lipid peroxidation. Lipid peroxidation is increased in AD brains andis believed to play a key role in driving neurodegeneration of AD. However, supplementation of lipid solubleantioxidants yields only mixed results in clinical trials. So the importance of lipid peroxidation in AD remainsunproven.

The goals of this application are to evaluate social buffering effects on cognitive decline associated with aging, as well as investigate potential biological markers of brain aging.

Bone fragility fractures are a major concern of health care of rapidly aging populations due to the high

risk of long-term disability and even mortality. Such fractures are not only due to loss of bone mineral density

(BMD), but also due to adverse changes at different structural hierarchies of bone, including ultrastructural

changes observed in bone disorders (e.g. osteogenesis imperfecta, mucopolysaccharidosis, and age-related

Overview: Lorisiform primates represent almost 10% of the living primate species; however, their taxonomy, evolutionary history, and biogeography are still poorly understood. Indeed, a major limitation to investigations of primate evolutionary history is the ability to obtain high quality genetic data across the entire geographic distribution of a taxon. Low quality samples, lack of geographic resolution, and access to wild populations have been some of the many limitations that have negatively impacted the field of primate phylogenetics.

We propose to repurpose an FDA-aproved drug for enhancing cellular function and improving general health. Our specific hypothesis is that Temsirolimus will reverse age-associated decline seen in general activity, sleep, mental activity, and movement in aged baboons. In this pilot study, we will evaluate the effect of 2 doses of Temsirolimus over a 10 months period on the health status of mitochondria, daytime activity, sleep, and motor and mental functions in aged baboons.

The research proposed here aims to optimize the delivery and functionality of a novel, biological therapy that bypasses the broad immunosuppressive mechanisms of current drugs in primary T cells, thereby addressing a major potential hurdle for this therapy.