The NIH is out to get at the root of senescence — a phenomenon causally linked to aging and age-related diseases in which cells stop dividing. And to do so, the NIH Common Fund has established the Cellular Senescence Network (SenNet) Program to comprehensively identify and characterize the differences in senescent cells across the body, various states of human health, and lifespan. SenNet will provide publicly accessible atlases of senescent cells, their differences, and the molecules they secrete, 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.”

To identify and characterize these rare cells, SenNet will develop innovative tools and technologies that build upon previous advances in single-cell analysis, such as those from the Common Fund’s Human Biomolecular Atlas Program and Single Cell Analysis Program. Lastly, SenNet aims to unite cellular senescence researchers by developing standard terms and classifications for senescent cells.

Why focus on senescence?

Senescent cells promote chronic low-level inflammation by secreting a collection of inflammatory and other molecules known as the senescence-associated secretory phenotype (SASP). The SASP is of great interest to researchers studying aging biology because it can profoundly affect tissue structure and function. But the field is challenged by a lack of standard terms and classifications for senescent cells.

“The trans-NIH approach of the SenNet program will provide tools and technologies capable of studying senescent cells in all their biological roles,” said James M. Anderson, M.D., Ph.D., director of the Division of Program Coordination, Planning, and Strategic Initiatives, which oversees the Common Fund.

“SenNet researchers will capitalize on recent advances in single-cell analysis, including those from the Common Fund’s Human Biomolecular Atlas Program and Single Cell Analysis Program, to create this foundational resource for the broader biomedical research community.”

NIH is funding $125 million to 16 grants over five years

the NIH is funding $125 million to 16 grants over five years, pending available funds:

·     Eight awards for the creation of SenNet Tissue Mapping Centers
·     Seven awards for Technology Development and Application Projects
·     One award for a Consortium Organization and Data Coordinating Center (CODCC)

The CODCC will act as a library for the consortium, developing something like the Dewey Decimal System to annotate and organize the vast collection of maps produced by the other teams. Eventually, the atlas of cellular senescence will be published online in an open-source repository so that other researchers can explore these data to make discoveries about senescent cells and how they contribute to human health. 

“I think that the science of senescent cells is tremendously exciting because of their potential impact on a whole variety of diseases,” said Jonathan Silverstein, M.D., professor in the Department of Biomedical Informatics at Pitt and chief research informatics officer at Pitt and UPMC’s Institute for Precision Medicine.

“By doing the basic science of collecting all of this information and presenting it through SenNet, there is incredible potential to learn more about the role these cells play in disease and develop pharmaceuticals that target them.” 

(Roy et al., 2020 | Cell) Five Broad Objectives to Help Build a Comprehensive Blueprint of Senescent Cells in Human Tissues and Organs. These five objectives are building a multimodal and multidimensional senescent cell atlas (Atlas); identifying a panel of reliable biomarkers (Biomarkers); imaging and visualizing (Imaging & visualization), including artificial intelligence tools to identify senescent cells; establishing experimental model systems (Model systems); and validation experiments (Perturbation & validation) via perturbation to test predictive models.

The awards include:

Brown University: Spatial omics technologies to map the senescent cell microenvironment

Buck Institute for Research on Aging: Senescent cell mapping, identification, and validation for human somatic and reproductive tissues

Buck Institute for Research on Aging: Evaluating diverse technologies for detecting and validating senescent cells in vivo

Columbia University: A Multi-scale Atlas of Senescence in Diverse Tissue Types

Duke University: The Duke Senescent Cell Evaluations in Normal Tissues (SCENT) Mapping Center

Massachusetts General Hospital: Single-cell proteomic identification of novel markers of senescence

Mayo Clinic Rochester: Development of machine learning software to quantitatively map telomere induced senescence in tissue sections during aging

Stanford University: Cellular Senescence Network: New Imaging Tools for Arthritis Imaging

University of Connecticut: The KAPP-Sen Tissue Mapping Center Collaborative

University of Michigan at Ann Arbor: Seq-Scope Microscopic Examination of Spatial Single-Cell Transcriptome in Cell and Tissue Senescence

University of Minnesota: Minnesota Tissue Mapping Center for Senescent Cells

University of Pittsburgh: TriState SenNET (Lung and Heart) Tissue Map and Atlas consortium

University of Pittsburgh: Cellular Senescence Network (SenNet) Consortium Organization and Data Coordinating Center (CODCC)

University of Washington: PIXEL-seq-based spatial, multi-omic profiling for senescent cell mapping with single-cell resolution

Washington University: Washington University Senescence Tissue Mapping Center (WU-SN-TMC)

Yale University: Yale TMC for Cellular Senescence in Lymphoid Organs

Buck Institute professor Judith Campisi, Ph.D., commented, “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 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.”