The Journey to Illuminating the Biological Mysteries of Healthy Aging

University of Minnesota Medical School researchers were awarded $19.3 million in NIH grants to identify and molecularly map senescent cells.

The road to discovering more about what drives our bodies to age may lead to informing potential therapeutics for many age-related conditions and improvements in a healthy life span.

Researchers from the Institute on the Biology of Aging and Metabolism (iBAM) at the University of Minnesota Medical School, Mayo Clinic and Northwestern University are addressing that challenge by collectively coming together to identify and map senescent cells in humans and mice as a function of aging.

Senescence is a cellular response to trauma, damage or stress known to contribute to aging. Senescent cells have both positive and negative effects on our health. “Understanding these and being able to discriminate between them is going to be very impactful to biomedicine,” says Laura Niedernhofer, MD, PhD, the director of iBAM and a professor in the Department of Biochemistry, Molecular Biology and Biophysics.

This multi-institutional effort is referred to as SenNet and consists of two grants to the Medical School. Each grant supports a tissue mapping center. Dr. Niedernhofer will lead a project focused on human tissue supported by a five-year grant worth $8.5 million to focus on human tissue. While David Bernlohr, PhD, a professor and head of the Department of Biochemistry, Molecular Biology in Biophysics, is leading a project focused on mouse tissue supported by a four-year companion grant worth $10.8 million.

“This large tissue mapping center focuses on identifying senescent cells in the healthy mice as a function of aging and sets the stage for future things that are going to be more translational,” states Dr. Bernlohr.

Altogether, the $19.3 million award is funded by the National Institutes of Health Common Fund. Not only is this project essential to the science behind aging, but it impacts all NIH institutes. The project involves curiosity-driven science led by nearly 60 principal investigators. The impact of these awards is significant, as researchers say it will require novel spatial technologies and yield large data sets, allowing them to advance the science, and bring foundational information to develop other projects in the future.

“The hope is that by defining normal senescence during a normal aging period, we would then be able to apply that information in the future to disease states which could yield novel therapeutic approaches targeting senescent cells,” Dr. Bernlohr explains.

The U of M Medical School and the Mayo Clinic have been at the forefront of developing senolytics, drugs that target senescent cells. Dr. Niedernhofer says that it is advantageous to our drug development program to learn more about senescent cells and their unique characteristics that can be therapeutically targeted.

“A huge component of this is generating a lot of data about senescent cells and then passing it off to bioinformaticians and computational biologists who can make sense of it. It's so much data that we require their input to create a four-dimensional atlas of senescent cells in the body. Our outstanding data analytical team is the same for both grants and led by the Institute for Health Informatics at U of M medical school,” shared Dr. Niedernhofer.

By gaining more data about various organs and cell types, they will provide crucial information that could lead to other approaches when thinking about healthy aging. The Institute for Healthcare Improvement and the University of Minnesota Genomics Center and Imaging Center is essential in this data analysis process.

Together, the researchers hope the SenNet project will lead to novel approaches to prevent or reverse age-related diseases, including Alzheimer's, cancer and genetic diseases where individuals age rapidly. “Stress drives senescence and aging as well. There are so many ways this research could impact health,” adds Dr. Niedernhofer.

“It’s extremely exciting because it’s a very ambitious project,” states Dr. Niedernhofer. “We don’t have the tools to get the job done perfectly currently in our hands. We’re betting we can build them, and it’s always fun to be on the building side of things.”