Yale researchers receive $12 million NIH grant to study impact of FGF21 protein on aging

Researchers from Yale University and the University of Texas Southwestern Medical Center have received a five-year, $12.4 million grant from the NIH’s National Institute on Aging to deploy their unique research designs and expertise in coordinated way to develop a new course of gerontological research.

Vishwa Deep Dixit, DVM, PhD, Waldemar Von Zedtwitz Professor of Pathology and Professor of Immunobiology and Comparative Medicine and Director of the Yale Center for Research on Aging (Y-Age), is the Project Grant Program Manager (PPG ). PPG’s Yale Principal Investigators include Tamas Horvath, DVM, PhD, the Jean and David W. Wallace Professor of Comparative Medicine and Professor of Neurosciences and Obstetrics, Gynecology, and Reproductive Sciences, and Chair of Comparative Medicine, and Joseph Schlessinger, the William H. Prusoff Professor of Pharmacology and co-director of the Yale Cancer Biology Institute.

The team has previously demonstrated that fibroblast growth factor 21 (FGF21), a hormonal protein encoded by the FGF21 gene, acts through an obligate co-receptor βKlotho (KLB) to control features of the process of aging such as inflammation, immune senescence and impaired energy metabolism. This project is based on new findings that specific overexpression of FGF21 in adipose tissue and thymus controls the aging of the organism and that FGF21, via AGRP neuron-mediated integration of hypothalamic and autonomic circuits, regulates aging.

“We will test the central hypothesis that FGF21 is a central gero-checkpoint that initiates a molecular prolonging program by integrating the neuro-metabolic and immune axes,” said Dr. Dixit. “The corollary is that pharmacological means to elevate FGF21 signaling by novel agonist variants of FGF21 may serve as therapy to prolong lifespan and lifespan.”

The PPG includes three projects:

  • Dr. Dixit will test the impact of FGF21 on immune senescence
  • Phillip Scherer, PhD, Professor, Department of Internal Medicine, UTSW, will define the role of fat-derived FGF21 on aging and metabolic dysfunction
  • Drs. Horvath and Schlessinger will investigate neural-induced signal transduction of the hypothalamic AGRP FGF21 toward organism aging

The PPG will be managed by the Y-Age research team and its core, which will support health and lifespan studies.

“We anticipate that the successful implementation of the proposed targets will lead to a generation of new knowledge that will enable the development of new strategies to exploit the geroprotective effects of FGF21 against aging and chronic disease,” said Dr. Dixit.

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