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The presence of senescent cells has been implicated in a wide range of age-related diseases and even conditions such as T1 diabetes. Today, we want to draw your attention to a new publication that explores the relationship between senescent cells and intervertebral disc degeneration (IDD).

It was already known that senescent cells increase during the progression of IDD, but it was not known if they were a driver or a consequence of IDD.

What are senescent cells?

As we grow older, our cells enter into a state known as senescence. Senescent cells cease to divide and begin to secrete a range of harmful chemical signals that cause inflammation, support the onset of various diseases, and disrupt the function of other nearby healthy cells, causing them to also become senescent. Senescent cells are thought to be one of the reasons we age.

Senescent cells usually destroy themselves via a kind of self-destruct mechanism known as apoptosis and are disposed of by the immune system. However, the immune system begins to fail with age, and increasing numbers of senescent cells evade apoptosis and remain at large, causing inflammation throughout the body.

By the time people have reached old age, significant numbers of senescent cells have accumulated in the tissues and organs, causing chronic inflammation and impaired tissue repair [1-2].

Senescent cells secrete proinflammatory cytokines, chemokines, and extracellular matrix proteases, which, together, form the senescence-associated secretory phenotype (SASP). The SASP is thought to significantly contribute to aging [3] and cancer [4]; thus, targeting senescent cells and removing them has been suggested as a potential solution to this problem.

Senescent cells in intervertebral disc degeneration

Age-related changes to the intervertebral discs are a primary cause of back pain as we grow older, and these researchers wondered if senescent cells were driving this process or were merely present as a symptom of IDD.

To test this, they used p16‐3MR transgenic mice, which are engineered to purge their senescent cells when exposed to the drug ganciclovir, an antiviral medication used to treat cytomegalovirus (CMV) infections.

The mice treated with ganciclovir saw a decrease in disc degeneration and an improvement in disc structure. The researchers also noted that reducing the number of senescent cells present also lowered the level of matrix protease MMP13 which is linked to age-related degenerative changes to discs.

Abstract

Rationale

Age‐related changes in the intervertebral discs are the predominant contributors to back pain, a common physical and functional impairment experienced by older persons. Cellular senescence, a process wherein cells undergo growth arrest and chronically secrete numerous inflammatory molecules and proteases, has been reported to cause decline in the health and function of multiple tissues with age. Although senescent cells have been reported to increase in intervertebral degeneration (IDD), it is not known whether they are causative in age‐related IDD.

Objective

The study aimed to elucidate whether a causal relationship exists between cellular senescence and age‐related IDD.

Methods and Results

To examine the impact of senescent cells on age‐associated IDD, we used p16‐3MR transgenic mice, which enables the selective removal of p16Ink4a‐positive senescent cells by the drug ganciclovir. Disc cellularity, aggrecan content and fragmentation alongside expression of inflammatory cytokine (IL‐6) and matrix proteases (ADAMTS4 and MMP13) in discs of p16‐3MR mice treated with GCV and untreated controls were assessed. In aged mice, reducing the percent of senescent cells decreased disc aggrecan proteolytic degradation and increased overall proteoglycan matrix content along with improved histological disc features. Additionally, reduction of senescent cells lowered the levels of MMP13, which is purported to promote disc degenerative changes during aging.

Conclusion

The presence of senescent cells is linked to an ever-increasing number of age-related diseases and conditions. It is also becoming increasingly clear that removing these harmful cells presents a therapeutic opportunity and that clearing these cells appears to ameliorate age-related changes.

In the case of IDD, removing senescent cells appears to improve structure and may potentially delay further age-related disc degeneration. Given that back pain can seriously hamper quality of life and the ability of older people to function and get around, senescent cell-clearing therapies (senolytics) could be a solution to helping them maintain their independence and mobility.

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Literature

[1] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[2] van Deursen, J. M. (2014). The role of senescent cells in ageing. Nature, 509(7501), 439-446.

[3] Freund, A., Orjalo, A. V., Desprez, P. Y., & Campisi, J. (2010). Inflammatory networks during cellular senescence: causes and consequences. Trends in molecular medicine, 16(5), 238-246.

[4] Coppé, J. P., Desprez, P. Y., Krtolica, A., & Campisi, J. (2010). The senescence-associated secretory phenotype: the dark side of tumor suppression. Annual review of pathology, 5, 99.

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 as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, 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. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.
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