Multiple researchers at the Jackson Laboratory are taking part in an ambitious research programme spanning several top research institutions to study senescent cells. Senescent cells stop dividing in response to stressors and seemingly have a role to play in human health and the ageing process. Recent research with 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 – known as senotherapeutics – also improve the health of humans 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 an extensive research initiative for this very purpose.
The SenNet Consortium, a collaboration of institutions from throughout the US, was initially launched in 2021 with centres established to gather and analsze human data. The researchers will collect and analyse 18 tissues from healthy humans across the lifespan to discern the full scope of senescent cells and how they may contribute to the ageing process. The findings of the SenNet Consortium were recently presented in the journal Nature Aging.
Along with colleagues from the Mayo Clinic, the University of Texas Health Science centre at San Antonio, and UConn Health, JAX Professor Paul Robson, PhD is taking part 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 Data Analysis Core of KAPP-Sen TMC is led by JAX Associate Professor Duygu Ucar, PhD and JAX Professor Jeff Chuang, PhD
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 on Aging. JAX-Sen is led by Professor and Maxine Groffsky Endowed Chair Nadia Rosenthal, PhD with co-principal investigators Robson, JAX Associate Professor Ron Korstanje, PhD, and UConn Health’s Ming Xu, PhD. Associate professor Sheng Li and principal computational scientist Matt Mahoney led the Data Analysis Core of the JAX-Sen TMC.
JAX is poised to make substantial contributions to SenNet by profiling senescent cells in the kidney, placenta, pancreas, and heart, all tissues that are relevant to chronic diseases of ageing. The team will draw upon its genetically diverse mouse resources, including Diversity Outbred mouse populations, to model a range of molecular senescence traits, as well as inbred mice specifically engineered to help visualize senescent cell subsets.
As 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 to build the human-mouse interface. The goal of SenNet goes beyond building an atlas of senescent cells in the body and knowing more about senescent cell biology. The potential benefits of senotherapeutics for healthy human ageing are exciting, as are other possible clinical advances, such as identifying individuals at higher risk for age-related disease.
