Comparative Genomics of Longevity in Mammals

Ancestral mammals typically had the size of mouse, presumably with short lifespan as seen in modern mammals in similar ecological niches. After the extinction of large dinosaurs at the Cretaceous-Paleogene boundary, mammals diversified not only in ecological niches, but also in lifespan and body mass. Long-lived and large mammals faced common problems to solve, such as anti-aging and cancer-resistance. The longer an animal lives and the larger it grows, the more superior anti-aging and cancer-resistance mechanisms it requires. However, the molecular mechanisms behind the longevity in mammals remain largely unclear. It is our goal to unravel the mechanisms of longevity in mammals and eventually apply to human aging and cancer biology to improve human health.

The high-coverage sequencing of >20 mammalian genomes provides extremely valuable information for the evolution of longevity in mammals. We have analyzed mitochondrial genomes of hudreds of animal species and uncovered an important mechanism related to mtDNA replication for the instability of mitochondrial genomes that, together with metabolic rate, explains more than 50% of mammalian lifespan variances. We have also performed genome-wide scan in mammalian proteomes that discovered hundreds of longevity genes, and we are continuing to refine our analysis.

A strength of our lab is that we have a variety of people with deep background in evolutionary theory, computational analysis and molecular and cellular biology. A new and ongoing project in our lab is to provide better predictions of longevity genes, uncover novel targets for aging and cancer research, test the molecular and cellular functions (such as DNA repair, apoptosis, cell proliferation and mitochondrial function) of these longevity genes, uncover the molecular mechanisms for their functions, and eventually test in mouse models. This exciting project may lead to better understanding of the mechanisms of longevity in mammals, specially in species with superior anti-aging and anti-cancer mechanisms than humans, and eventually provide information on the best way to improve human health.

For more information about our ongoing project of comparative genomics of longevity in mammals, please contact Professor Gorbunova and Professor Seluanov, or directly contact Jiang-Nan Yang ( jyang46[at]bio.rochester.edu ) who is the main graduate student responsible for the design and organization of this project.

Content last modified: May 13, 2013