Buck Institute professors Judith Campisi, PhD and Birgit Schilling PhD, have been awarded a $12 million grant from the NIH’s Common Fund to join the newly established Cellular Senescence Network (SenNet), a national “tissue and cell mapping” effort involving 13 research institutes. The initiative is aimed at understanding cellular senescence, a stress response which has been linked to numerous age-related diseases. The five-year grant will enable Buck researchers to identify and characterize senescent cells in human ovaries, breast tissue and skeletal muscle. A separate $672,000 grant to Buck professor Simon Melov, PhD, will involve evaluating diverse technologies for detecting and validating senescent cells in ovarian tissue utilizing modern ‘organ on a chip’ models in collaboration with Francesca Duncan, PhD.
“We are thrilled that the NIH is investing in studying cellular senescence in humans. We are very excited to join SenNet and are eager to add to the knowledge base, which will be available to researchers around the world,” said Campisi, who is recognized as a pioneer in in the field. “We also look forward to interacting with the other SenNet awardees as we all work toward the same goal of accelerating the development of therapeutics to improve human health. This is a great time to be doing research on aging and collaboration will be the key to the project’s success.”
Why focus on cellular senescence?
Senescent cells promote chronic low-level inflammation by spewing out a panoply of inflammatory and other molecules (known collectively as the SASP – the senescence-associated secretory phenotype) that can have profound effects on tissue structure and function. The SASP is of great interest to researchers who study aging biology; several biotech companies are developing therapeutics aimed at quelling the damaging effects of senescent cells. But the field is challenged by a lack of common terms and classifications for senescent cells. SenNet aims to unite cellular senescence researchers by providing publicly accessible atlases of senescent cells, the differences among them, and the molecules they release, using data collected from multiple human and model organism tissues.
“The number of senescent cells in a person’s body increases with age, which may reflect both an increase in the generation of these cells and a decreased ability of the aging immune system to regulate or eliminate these cells. This age-related accumulation of senescent cells leads to production of inflammatory molecules and corruption of healthy cells,” said Richard J. Hodes, M.D., director of the National Institute on Aging, part of NIH. “This can affect a person’s ability to withstand stress or illness, recuperate from injuries, and maintain normal brain function. The aim of NIH’s strengthened focus on this field of science is to one day conquer these and other challenges.”
SenNet at the Buck
The SenNet award involves multiple labs at the Buck. Co-Principal Investigator Schilling brings expertise in mass spectrometry and proteomics to the effort; her lab has extensively profiled the SASP of human cells and has generated a curated database available to researchers. “Becoming part of SenNet will allow us to apply our modern technologies to profile transciptomic senescence signatures at single cell resolution, we will determine spatial relationship and frequencies of senescent cells in various tissues, as well as linking these signatures back to human biofluid signatures, such as plasma and follicular fluid using novel proteomic workflows.” she said.
In this tissue mapping center award Melov and team will apply the latest emerging technologies for single nuclei sequencing (sNuc-Seq) and Digital Spatial Profiling (DSP) to achieve comprehensive spatial tissue mapping, and to discover unique senescent cell signatures (either single nuclei mRNA or protein) that will be confirmed in tissue sections.
Campisi says the three human tissue samples being studied at the Buck are particularly relevant to aging, given that the ovary ages first in the body and is associated with a fibro-inflammatory microenvironment, the breast exhibits a strong SASP with aging and has a high fat content which often contains senescent cells, and skeletal tissue because muscle deterioration is associated with sarcopenia, the most common cause of age-related frailty. “The human muscle biopsies will be obtained over time, with the interval between repeated biopsies being the longest ever attempted in molecular studies on human aging in muscle in both sexes,” she said. “We are well positioned and very excited to reveal the burden of cellular senescence across the lifespan in a manner that has never been done before.”
Other Buck scientists included in the grant include President and CEO Eric Verdin, MD, Chief Scientific Officer Malene Hansen, PhD, faculty members David Furman, PhD, Pankaj Kapahi, PhD, Daniel Winer, PhD, and Christopher Benz, MD, as well as assistant research professor Akos Gerencser, PhD, and Senior Staff Scientist Gary Scott, PhD.
Funding is provided by NIH grant 1 U54 AG075932 “Senescent cell mapping, identification and validation for human somatic and reproductive tissues,” and 1 UG3 CA268105 “Evaluating diverse technologies for detecting and validating senescent cells in vivo”
About the NIH Common Fund: The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs. Common Fund programs are managed by the Office of Strategic Coordination in the Division of Program Coordination, Planning, and Strategic Initiatives in the NIH Office of the Director in partnership with the NIH Institutes, Centers, and Offices. More information is available at the Common Fund website: https://commonfund.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov
About the Buck Institute for Research on Aging
At the Buck, we aim to end the threat of age-related diseases for this and future generations. We bring together the most capable and passionate scientists from a broad range of disciplines to study mechanisms of aging and to identify therapeutics that slow down aging. Our goal is to increase human health span, or the healthy years of life. Located just north of San Francisco, we are globally recognized as the pioneer and leader in efforts to target aging, the number one risk factor for serious diseases including Alzheimer’s, Parkinson’s, cancer, macular degeneration, heart disease, and diabetes. The Buck wants to help people live better longer. Our success will ultimately change healthcare. Learn more at: https://buckinstitute.org