One of the oft cited “hallmarks of aging” is cellular senescence, but not everyone is familiar with what this means (Leung et al.). It is a state cells go into under certain conditions, commonly thought to be a defense against cancer, cells begin going into senescence under a variety of conditions believed to signal risk of tumor growth to the cell (Burton, 1-4).
Our sister company, BioViva Science, provides a test to gauge your body’s cellular senescence burden.
The trade-off is that senescent cells stop dividing, which means the body has fewer resources to maintain its systems, which in turn leads to imbalances in the body, leading to even more senescent cells (Patric). It is easy to see how this is, up to a certain point, a lifesaving function of the cell. The body may be deprived of resources, but so are potential tumors. Such a feature probably emerged as part of the evolutionary war between organisms and the tumors which would kill them without protocols in place to stop them (Kowald et al, 6-12.)
Cellular senescence is a war of attrition and can very much be understood as a core part of aging. Our bodies fight valiantly against the specter of cancer, but in doing so they lose a little ground, leave the battle weaker, and eventually, so many cells have been sacrificed, have become senescent, that the organism can no longer sustain itself. In other words, it dies of old age (Childs et al, 1424-1430.)
If we could make it so that less of our cells become senescent, or better yet, allow senescent cells to resume divisions, there might not be much of a fundamental difference between that and reversing aging, at least in part (Patric). This is the reason why cellular senescence is considered a hallmark of aging, it is one of the factors which, if better understood, would reveal a lot about how aging works. A cure for cellular senescence might work as a complete, or at least partial cure, for aging as it is.
The perceived danger of senescent cells go beyond a simple lack of productivity, however. Cells generally reproduce, senescent cells do not, but still accumulate energy. It is believed that instead of replicating, producing offspring, these cells produce unwanted byproducts. It is hypothesized that one such “byproduct” of senescent cells are cytokines, which encourage an overactive immune system, thereby accelerating the aging process (Franceschi et al, 581-590).
However, because senescent cells play a role in preventing growth in tumors, as well as in other processes, this is not a question of simply eliminating senescence, but instead, understanding how to manage senescence in concert with other processes to extend human health span (Iop et al, 1-6). Because while senescent cells may play a certain role, they eventually cause others and accelerate the deaths of their hosts.
Cellular senescence, like so many other parts of biology, is intricately connected to other processes. Maintaining health in any one of the bodies various systems and micro-environments can slow the accumulation of senescent cells. So can maintaining or lengthening telomeres, which is associated with a marked increase in life and health span (Moller et al, 761-770). Telomerases are kinds of protective caps on the end of DNA, over time the gradual shortening of these signals to the cell that damage may be occurring, which leads to the cells becoming senescent to protect themselves.
Telomerase lengthening treatments are already provided by Integrated Health Systems, this is not the only thing which regulates cellular senescence, but certainly a contributing factor. One of the interesting qualities of health interventions is that they can have cumulative effects, as we gain ground, it becomes easier to take, both in terms of the science and as the treatments are applied.
Someone who has had interventions of one kind is likely to see improvements in an array of areas. Telomerase lengthening is just one improvement, but that improvement leads to other improvements over time. Genomic stability can engender molecular stability, encourage the body to generate the kinds of proteins associated with youth simply because it senses that the body is more useful. The further upstream a solution is, the more likely it is that the rest of the body will be able to respond to that solution and that a cure will have more permanency.
And that is the quest of the century for medicine and genetics, to find a solution which not only reverses aging, but can prevent it from happening altogether, because it makes the body’s other systems fall into place.
References and Further Reading
Childs, Bennett G et al. “Cellular senescence in aging and age-related disease: from mechanisms to therapy.” Nature medicine vol. 21,12 (2015): 1424-35. doi:10.1038/nm.4000
Burton, D. “Cellular Senescence, Ageing and Disease.” Age, vol. 31, no. 1, Mar.
2009, pp. 1–9. EBSCOhost, doi:10.1007/s11357-008-9075-y.
Franceschi, Claudio, et al. “Inflammaging: a New Immune–Metabolic Viewpoint
for Age-Related Diseases.” Nature Reviews Endocrinology, vol. 14, no. 10, 2018, pp. 576–590., doi:10.1038/s41574-018-0059-4.
Iop, Laura, et al. “The Light and Shadow of Senescence and Inflammation in
Cardiovascular Pathology and Regenerative Medicine.” Mediators of Inflammation, Oct. 2017, pp. 1–13. EBSCOhost, doi:10.1155/2017/7953486.
Kowald, Axel, et al. “On the Evolution of Cellular Senescence.” Aging Cell, vol.
19, no. 12, Dec. 2020, pp. 1–12. EBSCOhost, doi:10.1111/acel.13270.
Leung, Diana L, et al. “Epigenetic Profiles Of Biological Aging Hallmarks.”
Innovation in Aging, vol. 3, no. Supplement_1, 2019, doi:10.1093/geroni/igz038.1584.
Møller, Peter, et al. “Telomere Dynamics and Cellular Senescence: An Emerging
Field in Environmental and Occupational Toxicology.” Critical Reviews in Toxicology, vol. 48, no. 9, Oct. 2018, pp. 761–788. EBSCOhost, doi:10.1080/10408444.2018.1538201.
Patric, Rhonda, director. Judith Campisi, Ph.D. on Cellular Senescence,
Mitochondrial Dysfunction, Cancer & Aging. Youtube, Found My Fitness, 28 Apr. 2017, www.youtube.com/watch?v=adg3vUez3EU. This interview provides a nice overview of senescence as it relates to aging.
Perrott, Kevin, director. Targeting the Senescence-Associated Secretory
Phenotype – Kevin Perrott. Youtube, SENS Foundation, 3 Feb. 2014, www.youtube.com/watch?v=m8OiyOoFLeM. This presentation provides information on the senescence-associated secretory phenotype, which we were unable to touch on directly in this blog post, but is essential to a more detailed understanding of how senescent cells can be influential.
Ryo Okuda, et al. “Cellular Senescence and Senescence-Associated Secretory
Phenotype: Comparison of Idiopathic Pulmonary Fibrosis, Connective Tissue Disease-Associated Interstitial Lung Disease, and Chronic Obstructive Pulmonary Disease.” Journal of Thoracic Disease, vol. 11, no. 3, Mar. 2019, pp. 857–864. EBSCOhost, doi:10.21037/jtd.2019.02.11.
Suram, Anitha, and Utz Herbig. “The Replicometer Is Broken: Telomeres Activate
Cellular Senescence in Response to Genotoxic Stresses.” Aging Cell, vol. 13, no. 5, Oct. 2014, pp. 780–786. EBSCOhost, doi:10.1111/acel.12246.