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Building an Atlas of Senescent Cell Secretions

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Recently, a team of researchers, including Professor Judy Campisi, has published an atlas charting the inflammatory senescence-associated secretory phenotype (SASP) [1].

The nature of the SASP

As we grow older, increasing numbers of our cells enter a state known as senescence. Senescent cells no longer divide to support and help maintain the tissues that they are a part of and instead secrete a range of harmful inflammatory signals: the SASP.

The SASP contributes to the chronic background of inflammation that is typically seen in older people and facilitates the development of a multitude of age-related diseases. Worse still, it can also cause nearby healthy cells to become senescent through exposure.

Because of how harmful the SASP is, it has been proposed that therapies that remove excessive senescent cells could delay, prevent, and even reverse certain age-related diseases. These therapies are known as senolytics, a class of drugs or interventions that encourage senescent cells to destroy themselves via a process known as apoptosis.



Normally, apoptosis occurs naturally as part of our waste disposal system, removing damaged and non-dividing senescent cells to maintain healthy tissues and organs. However, as we age, the removal of these problem cells begins to decline until, eventually, they build up to excessive levels and dump their harmful SASP into the bloodstream, impairing tissue repair and driving disease development.

The accumulation of senescent cells and the resulting SASP is one of the hallmarks of aging.

Building a SASP Atlas

Prof. Campisi’s team of researchers has created a full database of the chemicals expressed in the SASP, including proteins and factors secreted in exosomes, which cells use to communicate. This new atlas represents the culmination of many years of research in which researchers have been exploring the various molecules secreted by senescent cells in order to create a comprehensive database that the research community can use.

The senescence-associated secretory phenotype (SASP) has recently emerged as a driver of and promising therapeutic target for multiple age-related conditions, ranging from neurodegeneration to cancer. The complexity of the SASP, typically assessed by a few dozen secreted proteins, has been greatly underestimated, and a small set of factors cannot explain the diverse phenotypes it produces in vivo. Here, we present the “SASP Atlas,” a comprehensive proteomic database of soluble proteins and exosomal cargo SASP factors originating from multiple senescence inducers and cell types. Each profile consists of hundreds of largely distinct proteins but also includes a subset of proteins elevated in all SASPs. Our analyses identify several candidate biomarkers of cellular senescence that overlap with aging markers in human plasma, including Growth/differentiation factor 15 (GDF15), stanniocalcin 1 (STC1), and serine protease inhibitors (SERPINs), which significantly correlated with age in plasma from a human cohort, the Baltimore Longitudinal Study of Aging (BLSA). Our findings will facilitate the identification of proteins characteristic of senescence-associated phenotypes and catalog potential senescence biomarkers to assess the burden, originating stimulus, and tissue of origin of senescent cells in vivo.

Conclusion



This atlas does a public service for the research community, and we hope such collaborative efforts to chart processes such as the SASP continue to develop. It is clear that there are many nuances to senescent cells and the molecules they secrete, and understanding them further will help researchers to develop more clinically relevant biomarkers for detecting their presence and thus to develop effective therapies for humans. This atlas goes a long way towards this end, and we are delighted to see its publication.

Literature

[1] Basisty, N., Kale, A., Jeon, O. H., Kuehnemann, C., Payne, T., Rao, C., … & Campisi, J. (2020). A proteomic atlas of senescence-associated secretomes for aging biomarker development. PLoS biology, 18(1), e3000599.



About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
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