Mammalian Aging Group
Molecular Mechanisms of Aging
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Xiaoling Li, Ph.D.
Principal Investigator -
Tel (919) 541-9817
Fax (919) 541-1898
lix3@niehs.nih.gov -
P.O. Box 12233
Mail Drop F1-09
Research Triangle Park, North Carolina 27709
Delivery Instructions
Research Summary
Aging, the decline in survival and fecundity with age, is one certainty of life. It has long been known that both genetic factors and environmental influences contribute to the progress of aging, yet the underlying molecular mechanisms remain unclear. In the last two decades, a major breakthrough in the aging field is the identification of a few genetic pathways that play master regulatory roles in the aging process. One such genetic pathway is mediated by sirtuins. Sirtuins are a highly conserved family of NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that target histones, transcription factors, co-factors, as well as numerous other key regulators. These NAD+-dependent activities enable sirtuins to monitor cellular energy status and modulate gene transcription, energy metabolism, genome stability that affect aging, thus controlling the delicate balance between metabolism and aging. These activities are also important for cell survival in response to various environmental stressors and are required for lifespan extension provided by calorie restriction (CR) in a number of model organisms. Therefore, sirtuins are considered to be essential genetic factors that directly link the environment to aging, providing us a unique opportunity to study gene-environment interactions during the aging process.
The long-term goal of the Mammalian Aging Group is to understand signal transduction that coordinates the gene-environment interaction during the process of aging and investigate how dysregulation of this interplay contributes to pathogenesis of age-associated diseases. To pursue these research goals, the laboratory focuses on SIRT1, the most conserved mammalian sirtuin. Utilizing the mouse and culture cells as model systems, the group combines molecular, cellular, and genetic approaches to study the role of SIRT1 in the regulate of metabolism, stress response, reproduction, and ultimately aging.
Major areas of research:
- The role of SIRT1 in transcriptional responses, particularly nuclear receptor mediated signaling
- The role of SIRT1 in metabolic diseases associated with aging
- The regulation of SIRT1’s activity in response to various environmental, nutritional, and hormonal cues
Current projects:
- Investigate the function of hepatic SIRT1 in fatty acid metabolism and cholesterol homeostasis
- Study the role of SIRT1 in age-associated metabolic diseases
- Understand the molecular mechanisms underlying the phosphorylation regulation of SIRT1
- Identification of other signaling pathways regulated by sirtuins
Xiaoling Li, Ph.D., heads the Mammalian Aging Group within the Laboratory of Signal Transduction (LST). She received her Ph.D. in Biological Chemistry from The Johns Hopkins School of Medicine in 2002. She has published a number of peer-reviewed articles in leading biomedical journals. She served as a Leukemia & Lymphoma Society Postdoctoral Fellow in the laboratory of Leonard Guarente at Massachusetts Institute of Technology before joining NIEHS in 2007.
