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.

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.

Emerging evidence supports the proposition that the mitochondrial respiratory chain (MRC) functions viaorganized multicomplex structures called supercomplexes. However the dynamics and regulation ofsupercomplex assembly have not been fully investigated. In particular, hardly any regulatory protein factorsinvolved in supercomplex assembly have been identified. Our long term goal is to understand the dynamics ofmitochondrial respiratory machinery and its underling regulatory mechanism.