Understanding senescent cell biology and healthy aging

Understanding senescent cell biology and healthy aging

Several Jackson Laboratory researchers are participating in an ambitious research program spanning 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 eliminating senescent cells delays the onset of age-related dysfunction and disease, as well as all-cause mortality.

Could therapies that eliminate senescent cells – called senotherapy – also improve human health as we age? Answering this question and more has the potential to significantly advance human health, and the National Institutes of Health (NIH) has launched a massive research initiative with just that goal.

The SenNet Consortium, a collaboration of institutions across the United States, was originally launched in 2021 with centers created to collect and analyze human data. Researchers will collect and analyze 18 tissues from healthy humans 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 an article published in natural aging.

With colleagues from Mayo Clinic, University of Texas San Antonio Health Sciences Center, and UConn Health, JAX Professor Paul Robson, Ph.D. is helping map four types of human tissue (kidney, fat, pancreas and placenta) within the KAPP-Sen Tissue Mapping Center. The Robson Lab also leads the Biological Analysis Core, and KAPP-Sen TMC’s Data Analysis Core is led by JAX Associate Professor Duygu Ucar, Ph.D., and JAX Professor Jeff Chuang, Ph.D. .

SenNet has also expanded over the past year to add mouse-focused researchers, and JAX was designated as the Tissue Mapping Center (TMC) for SenNet in August 2022, supported by a $10.7 grant. million dollars over four years from the National Institute on Aging. JAX-Sen is led by Maxine Groffsky Professor and Chair Nadia Rosenthal, Ph.D., FMedSci with Co-Principal Investigators Robson, JAX Associate Professor Ron Korstanje, Ph.D., and Ming Xu, Ph. D. of UConn Health. Associate Professor Sheng Li and Senior Computational Scientist Matt Mahoney lead the data analysis core of the JAX-Sen TMC.

JAX is poised to make substantial contributions to SenNet by profiling senescent cells in kidney, placenta, pancreas, and heart, all tissues relevant to chronic diseases of aging. The team will draw on its resources of genetically diverse mice, including populations of Diversity Outbred mice, to model a range of molecular senescence traits, as well as specially engineered inbred mice to help visualize cell subsets senescent.

As three of the tissues (kidney, pancreas and placenta) of the JAX-Sen TMC mouse are shared with the human KAPP-Sen TMC, these efforts align well with the JAX institutional initiative to continue building the human-mouse interface. . SenNet’s goal goes beyond building an atlas of senescent cells in the body and learning more about senescent cell biology. The potential benefits of senotherapy for healthy human aging are exciting, as are other possible clinical advances, such as identifying those at higher risk for age-related diseases.

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