William Mair, Assistant Professor of Genetics and Complex Diseases

Our lab focusses on the molecular and genetic processes that govern the aging process. Aging is a universal trait that is observed across the evolutionary spectrum. From a public health perspective, aging is also the critical risk factor for a variety of human pathologies, including neurodegenerative diseases, many forms of cancer and metabolic disease. We are interested in understanding the molecular pathways underpinning aging, with the goal of using this knowledge to develop novel therapeutic strategies to treat age-onset disorders.

In particular, we study the mechanisms by which animals can modulate the rate at which they age in response to changes in nutrition and the environment. The profound ability to slow aging when energy availability is low is seen in organisms ranging from yeast to primates and is coupled to a striking protection against a suite of age-related pathologies. By elucidating the genetic and molecular pathways that dictate this response, we aim to recapitulate the positive effects of dietary restriction on lifespan and health without the need for changes in dietary intake and its associated detrimental side effects.

AMPK
An emerging central upstream regulator of the response to dietary restriction is the pro-longevity AMP-activated protein kinase (AMPK), a cellular energy sensor that functions as a critical fuel gauge, becoming activated during energy stress. One focus of our lab is identifying the longevity-specific processes regulated by AMPK using a combination of genetic and molecular approaches in both the nematode worm C. elegans and mammalian cell culture.

Education
Ph.D., 2005, Institute of Healthy Ageing, University College London.
Postdoctoral Training, The Salk Institute for Biological Studies, La Jolla, CA.
Selected Publications
Mair, W., Morantte, I., Rodrigues, A. P. C., Manning, G., Montminy, M., Shaw, R. J., and Dillin, A. (2011). Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB. Nature 470, 404–U179.
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., Asara, J.M., Fitzpatrick, J., Dillin, A., Viollet, B., Kundru, M., Hansen, M., Shaw, R. J. (2011). Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331, 456–461.
Mair, W., McLeod, C. J., Wang, L., and Jones, D. L. (2010). Dietary restriction enhances germline stem cell maintenance. Aging Cell 9, 916–918.
Mair, W., and Dillin, A. (2008). Aging and survival: the genetics of life span extension by dietary restriction. Annu. Rev. Biochem. 77, 727–754.
Mair, W., Piper, M. D. W., and Partridge, L. (2005). Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS Biol 3, e223.
Mair, W., Goymer, P., Pletcher, S. D., and Partridge, L. (2003). Demography of dietary restriction and death in Drosophila. Science 301, 1731–1733.