Numerous researchers at the Jackson Laboratory are participating in an ambitious research program involving several leading research institutions to study senescent cells. Senescent cells stop dividing in response to stressors and appear to have a role to play in human health and the aging process. Recent research in mice suggests that clearing senescent cells delays the onset of age-related dysfunction and disease, as well as all-cause mortality.
Could therapies that remove senescent cells—called senotherapeutics—also improve people’s health as we age? The answer to this question and more has the potential to significantly advance human health, and the National Institutes of Health (NIH) has launched a broad research initiative to do just that.
The SenNet Consortium, a collaboration of institutions from across the United States, was originally launched in 2021 with centers established to collect and analyze human data. Researchers will collect and analyze 18 tissues from healthy people across the lifespan to discern the full extent of senescent cells and how they may contribute to the aging process. The work of the SenNet Consortium was recently presented in a paper published in The aging of nature.
Along with colleagues from the Mayo Clinic, the University of Texas Health Science Center at San Antonio and UConn Health, JAX Professor Paul Robson, Ph.D. is participating in the mapping of four human tissue types (kidney, adipose, pancreas and placenta) within the KAPP-Sen Tissue Mapping Center. The Robson lab also leads the Biological Analysis Core, and the KAPP-Sen TMC Data Analysis Core is led by JAX Associate Professor Duygu Ucar, Ph.D., and JAX Professor Jeff Chuang, Ph.D.
SenNet has also grown over the past year to add mouse-focused investigators, and JAX was designated as a Tissue Mapping Center (TMC) for SenNet in August 2022, supported by a four-year, $10.7 million grant from the National Institute of Aging. JAX-Sen is led by Maxine Groffsky Endowed Professor and Chair Nadia Rosenthal, Ph.D., FMedSci with co-investigators Robson, JAX Associate Professor Ron Korstanje, Ph.D., and Ming Xu, Ph.D of UConn Health. Associate Professor Sheng Li and Principal Computer Scientist Matt Mahoney lead the data analysis core of the JAX-Sen TMC.
JAX is poised to make a significant contribution to SenNet by profiling senescent cells in the kidney, placenta, pancreas, and heart, all tissues that are relevant to chronic diseases of aging. The team will draw on its genetically diverse mouse resources, including Diversity Outbred mouse populations, to model a variety of molecular aging traits, as well as inbred mice specifically designed to help visualize cell subsets of aging.
Since three of the tissues (kidney, pancreas, and placenta) in the mouse JAX-Sen TMC are shared with the human KAPP-Sen TMC, these efforts align well with the JAX institutional initiative to continue building the human-mouse interface. The goal of SenNet goes beyond building an atlas of senescent cells in the body and learning more about the biology of senescent cells. The potential benefits of senotherapeutics for healthy human aging are exciting, as are other potential clinical advances, such as identifying individuals at higher risk for age-related diseases.
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