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A Biomarker Based on Senescent Cell Secretions

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Researchers have published a new study suggesting that some of the inflammatory signals secreted by senescent cells could be used as a biomarker to measure aging and health.

What are senescent cells?

As you age, increasing numbers of your cells enter into a state known as senescence. Senescent cells do not divide or support the tissues of which they are part; instead, they emit a range of harmful chemical signals known as the senescence-associated secretory phenotype, or SASP. The SASP contains a complex cocktail of factors including cytokines, chemokines, proteins, growth factors, and more.

This secreted SASP is what makes senescent cells such a problem, as it not only contributes to the chronic systemic inflammation known as inflammaging, it can also encourage nearby healthy cells to become senescent as well. This means that a relatively small number of senescent cells in tissue can have a very large impact on the health and function of that tissue.

The presence of senescent cells and their SASP has been implicated in a myriad of age-related diseases and conditions; this is why researchers are currently developing senolytics, therapies that can remove them from the body.



Using the SASP as a biomarker of aging

The researchers of a new study make the case for collectively using certain factors in the secreted SASP to form a biomarker of aging and health [1]. Within the complex cocktail of secreted proteins and molecules that make up the SASP, the researchers identified a total of seven factors that they believe give a reliable indication of biological age and relative health.

These factors are also easy to test given that they can be sampled via a simple blood draw and then fed into diagnostic testing equipment. This is critical because, in order to be clinically useful, biomarkers should be both cost-effective and accurate.

Produced by senescent cells, the senescence-associated secretory phenotype (SASP) is a potential driver of age-related dysfunction. We tested whether circulating concentrations of SASP proteins reflect age and medical risk in humans. We first screened senescent endothelial cells, fibroblasts, preadipocytes, epithelial cells, and myoblasts to identify candidates for human profiling. We then tested associations between circulating SASP proteins and clinical data from individuals throughout the life span and older adults undergoing surgery for prevalent but distinct age-related diseases. A community-based sample of people aged 20–90 years (retrospective cross-sectional) was studied to test associations between circulating SASP factors and chronological age. A subset of this cohort aged 60–90 years and separate cohorts of older adults undergoing surgery for severe aortic stenosis (prospective longitudinal) or ovarian cancer (prospective case-control) were studied to assess relationships between circulating concentrations of SASP proteins and biological age (determined by the accumulation of age-related health deficits) and/or postsurgical outcomes. We showed that SASP proteins were positively associated with age, frailty, and adverse postsurgery outcomes. A panel of 7 SASP factors composed of growth differentiation factor 15 (GDF15), TNF receptor superfamily member 6 (FAS), osteopontin (OPN), TNF receptor 1 (TNFR1), ACTIVIN A, chemokine (C-C motif) ligand 3 (CCL3), and IL-15 predicted adverse events markedly better than a single SASP protein or age. Our findings suggest that the circulating SASP may serve as a clinically useful candidate biomarker of age-related health and a powerful tool for interventional human studies.

Conclusion

This SASP-based biomarker could potentially prove useful in quantifying the presence and level of senescent cells, along with their subsequent health risks in older people. It could also have potential in measuring the reduction of said senescent cells, following senolytics and other therapies aimed at removing them from the body.



Quite simply, the more high-quality biomarkers of aging we have available, the easier it will be to confirm the efficacy of a therapy aimed at addressing the reasons we age. Using the components of the SASP to measure biological age, health, and risk factors for age-related diseases seems like a promising avenue of research.

Literature

[1] Schafer, M. J., Zhang, X., Kumar, A., Atkinson, E. J., Zhu, Y., Jachim, S., … & Kotajarvi, B. (2020). The senescence-associated secretome as an indicator of age and medical risk. JCI insight, 5(12).



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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