Understanding senescent cells’ secrets and how they affect ageing and human health

The Jackson Laboratory is one of several prominent research organisations involved in an ambitious endeavour to investigate senescent cells that involves numerous researchers from the Jackson Laboratory. Senescent cells appear to have a function in ageing and human health because they cease proliferating in response to stresses. Senescent cell clearance may postpone the development of age-related dysfunction and illness as well as all-cause mortality, according to recent mouse studies.

Could senotherapeutics, or treatments that eliminate senescent cells, enhance people’s health as they age? The National Institutes of Health (NIH) has undertaken a substantial research project with the goal of addressing these and other questions that have the potential to dramatically improve human health. With facilities set up to collect and analyse human data, the SenNet Consortium, a partnership of universities from throughout the United States, was originally launched in 2021. To understand the whole range of senescent cells and how they could affect the ageing process, the researchers will gather and examine 18 tissues from healthy adults throughout the course of their lives. Recently, a study from Nature Aging detailed the findings of the SenNet Consortium.

Paul Robson, Ph.D., a professor at JAX, is participating in the mapping of four human tissue types—kidney, adipose, pancreas, and placenta—with associates from the Mayo Clinic, University of Texas Health Science Center in San Antonio, and UConn Health. The Data Analysis Core of KAPP-Sen TMC is supervised by JAX Associate Professor Duygu Ucar, Ph.D., and JAX Professor Jeff Chuang, Ph.D., while the Biological Analysis Core is also under the direction of the Robson Lab.

SenNet has expanded over the past year to include researchers that specialise in mice, and in August 2022, JAX was named a Tissue Mapping Center (TMC) for SenNet, thanks to a four-year, $10.7 million funding from the National Institute on Aging. Associate Professor Sheng Li and Principal Computational Scientist Matt Mahoney oversee the Data Analysis Core of the JAX-Sen TMC, which is led by Professor and Maxine Groffsky Endowed Chair Nadia Rosenthal, Ph.D., FMedSci, Robson, JAX Associate Professor Ron Korstanje, Ph.D., and Ming Xu, Ph.D. from UConn Health.

Profiling senescent cells in the kidney, placenta, pancreas, and heart, all organs that are important for chronic disorders of ageing, will enable JAX to significantly advance SenNet. To replicate a variety of molecular senescence features, the team will employ its genetically varied mouse resources, including Diversity Outbred mouse populations and inbred mice particularly designed to aid in the visualisation of senescent cell subsets.

These initiatives fit nicely with the JAX institutional aim to continue developing the human-mouse interface since three tissues—the placenta, pancreas, and kidney—in the mouse JAX-Sen TMC and the human KAPP-Sen TMC are shared. SenNet’s objectives go beyond compiling an atlas of the body’s senescent cells and learning more about their biology.

Senotherapeutics’ potential advantages for healthy human ageing as well as other prospective clinical advancements including the ability to detect those who are more likely to develop age-related diseases are interesting.