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Mammalian Aging Group

Molecular Mechanisms of Aging

Xiaoling Li, Ph.D.
Xiaoling Li, Ph.D.
Principal Investigator

Tel (919) 541-9817
Fax (919) 541-1898
P.O. Box 12233
Mail Drop F1-09
Research Triangle Park, North Carolina 27709
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Research Summary

Aging is one certainty of life. Both genetic factors and environmental influences contribute to the progress of aging, yet the underlying molecular mechanisms are just starting to be appreciated. 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 of such genetic pathways is mediated by Silent information regulator 2 (Sir2). The Sir2 family of proteins (sirtuins) are NAD-dependent protein deacetylase or ADP-ribosyltransferase. In a variety of model organisms, sirtuins regulate aging and longevity in response to nutritional and hormonal cues.

The Mammalian Aging Group is interested in identifying environmental cues that sirtuins sense, and in determining how they affect the progress of aging and age-associated diseases. These studies will have the potential to lead to novel therapies for a number of age-associated diseases. In particular, the group focuses on understanding the roles that sirtuins play in the modification of nuclear receptors and the corresponding age-associated metabolic diseases. Nuclear receptors are sensors of a variety of environmental cues, including small metabolites in diets (e.g. cholesterol, fatty acids and fat-soluble vitamins) and steroid hormones. Dysfunctions of these receptors are linked to a number of age-associated metabolic diseases, including diabetes, obesity and atherosclerosis. The group has shown that SIRT1, a mammalian member of sirtuins, plays an important role in the regulation of cholesterol homeostasis through deacetylation of LXRs, nuclear receptors that are sensors of cholesterol metabolites. This study suggested that SIRT1 may directly participate in the decrease of the risk of cholesterol metabolic diseases.

Major areas of research:

  • The role of the Sir2 family of proteins (sirtuins) in regulating aging and longevity in response to nutritional and hormonal cues
  • The role of sirtuins in age-associated metabolic diseases

Current projects:

  • Investigation of the molecular mechanisms by which SIRT1 regulates the LXR signaling pathway
  • Study of the function of SIRT1 in LXR-related metabolic diseases
  • Identification of other nuclear receptors’ signaling pathways regulated by sirtuins

Xiaoling Li, Ph.D., heads the Mammalian Aging Group within the Laboratory of Signal Transduction.  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 at Massachusetts Institute of Technology before joining NIEHS in 2007.

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Last Reviewed: May 24, 2007