Principal Investigator Leonard Guarente
Co-investigator H Horvitz
Age is the biggest risk factor and a requirement for onset of many neurodegenerative diseases for reasons that remain unclear. Human brain aging is associated with specific and robust changes in the expression of 5-10% of the genome. These changes are highly reproducible and precise and tend to effect neurodegenerative disease genes disproportionally, suggesting that brain aging may be a “transcriptional program” that is permissive for neurodegenerative disease onset. It is one of our goals to understand how the human brain aging transcriptional program works and how it is regulated to pave the way for anti-aging therapeutic strategies for neurodegenerative disease. We are employing human post-mortem transcriptomic, whole genome SNP chips, epigenomic, and bioinformatic strategies to understand this problem. We have ongoing collaborations with other labs and clinicians at MIT, Harvard, and the Broad Institute, including the lab of Dr. Manolis Kellis (computational biology and epigenetics). We are particularly interested in the role of sirtuins in human brain aging and neurodegeneration. We are investigating the role of sirtuin levels and also sirtuin polymorphisms in regulating human brain aging rates and neurodegenerative disease risk as well as looking broadly using unbiased genome-wide strategies.