MedicalResearch: What is the background for this study? What are the main findings?
Dr. Mair: Dietary restriction, the reduction of food intake without malnutrition has been known for 80 years to prolong lifespan in organisms ranging from single celled yeast to non human primates, and early signs suggest improvement of metabolic parameters in patients undergoing clinical trials. However, negative side effects associated with low calorie intake remain, and compliance and lifestyle factors make it an unappealing therapeutic. Since calorie restriction (CR) can have remarkable protective effects against multiple age onset diseases in mouse models – ranging from cancer to neurodegeneration to metabolic disease – finding molecular mechanisms though which calorie restriction functions might provide novel therapeutic targets that promote healthy aging. Using a model system, the nematode worm C. elegans, we show that perception of energy intake in the nervous system may be as critical for the effects of low energy on aging as actual calorie intake itself. Animals expressing an active form of a protein called AMPK, which is a cellular energy sensor, were long lived despite eating normally but this longevity could be turned off or on by changes to a neurotransmitter in just a few neurons. This suggests that therapeutic targets that modulate the perception of energy status in the nervous system might provide novel ways to gain the benefit of calorie restriction and promote healthy aging.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. William Mair: Calorie restriction is a remarkable phenomenon as it has such a broad protective effect on age related diseases with very different proximal causes. Therefore understanding the links between energy intake and aging itself might be an alternative to disease centric approaches in biomedicine. The molecular mechanisms that mediate calorie restriction in the nervous system in C. elegans are conserved in mammals and deregulated during aging and obesity. If our results linking energy perception to healthy aging are similarly conserved to mammals, targeting these processes as broad spectrum therapeutics might one day become a reality.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. William Mair: Our goal is now to translate this work into a mammalian setting and understand how central nervous system regulation of peripheral metabolism might play a role in the beneficial effects of calorie restriction.
Burkewitz, K., Morantte, I., Weir, H. J. M., Yeo, R., Zhang, Y., Huynh, F. K., Ilkayeva., O. R., Hirschey, M. D., Grant, A. R., and Mair., W. B. Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal. Cell. In Press
MedicalResearch.com Interview with: William Mair, Ph.D (2015). Cellular Energy Sensor Links Calorie Restriction With Healthy Aging