Systems biology of Aging lab aims to identify novel functional connections between organs and to unravel factors that underlie human metabolism and its disorders. 

Our body is like a house. A house is constantly deteriorating due to external factors, such as sunlight and rain, internal factors such as rusting or woodworm. In the same way our organs can deteriorate due to factors that originate within and outside them. For example, alterations in the levels and/or action of certain cytokines or hormones can lead to changes in distant organ functions. The best example of this phenomenon is the loss of estrogen- an ovary-derived hormone after menopause, which results in changes in adiposity, glucose tolerance,  and bone mass. This fact underscores that systemic influences or molecules originating in other organs are central to the regulation of organ functions. Organs in turn often limit these signals originating in distant organs through feedback loops by secreting different molecules. Understanding the biology surrounding these networks have the potential to identify molecular targets to treat diseases of aging.

In humans it is known that vitamin B12 deficiency leads to several abnormalities. The underlying molecular processes however have remained poorly understood. Over the last decade we have identified a novel gut-liver-endocrine axis operational through vitamin B12 (B12) and delineated the road map of B12 action on growth and musculoskeletal system. Using a mouse genetic model of loss of function of gastric intrinsic factor (Gif), the protein that is essential for the absorption of B12, we have identified the pathway linking B12 action in the liver to other organs such as muscle and bone. In the liver B12 regulates in a GH-dependent manner production of taurine that is then released into the circulation and regulates several processes as a "hormone". These studies have also illustrated how changes in maternal nutrition and endocrine systems have lifelong consequences on offpsring physiology. The discovery of these unanticipated pathways between organ systems and the role of maternal axis in this process would not have been possible without the use of mouse molecular genetics and studies in the clinic that allowed us to understand interactions between organ systems. 

Current studies are aimed at unraveling the signaling pathways that regulate taurine-impacted endocrine axis during development, early postnatal life and aging. We continue to identify and investigate functions of other novel endocrine axis in this process that regulate organ health and investigate molecular interventions to treat degenerative diseases.

Thus the overall goal is to elucidate novel endocrine interactions between organ systems using mouse and human genetics to identify novel and adapted therapies to cure diseases of aging.