SPARC, secreted protein acidic and rich in cysteine, is a 32kDa calcium-binding matricellular protein. The matricellular proteins (thrombospondin-1, tenascin-C and SPARC) are extracellular matrix proteins that antagonize cell adhesions when presented to cells as soluble molecules. This proposal is based on our findings from CALERIE-II (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) a National Institute on Aging-sponsored randomized control trial in which healthy humans underwent 15% caloric restriction for a period of two years. The RNA sequencing analysis of adipose tissue derived from humans post-caloric restriction identified SPARC as the most highly expressed and most significantly downregulated gene. The proposal tests the hypothesis that microglial-specific SPARC downregulation will protect against age-related central nervous system inflammation, inflammasome activation, and
The process of aging is the single biggest risk factor for development of Alzheimer’s disease. The development of inflammation in a specialized brain cell type called microglia is thought to be responsible for neuronal death and dementia. This proposal will study a novel protein that controls inflammation in microglial cells to develop new approaches to protect against age-related loss of memory and cognition. This research builds on the idea that late-onset chronic diseases such as Alzheimer’s disease are the consequence of the prolonged overworking of various tissues with vulnerabilities. Proteins such as SPARC that are highly expressed in microglial activation could be a target for protecting against age-related loss of memory and cognition.