By treating one of the root causes of aging – senescent cells – a new class of drugs, known as senolytics, has the potential to treat a wide range of age-related diseases rather than the traditional approach of dealing with them one at a time.

Today we are going to take a look at what senescent cells are, how they contribute to age-related diseases and a new review by the Mayo Clinic that shows what we can do about this problem. We all age, but the research suggests that we may not have to suffer from age-related ill health.

So what are senescent cells?

As we age, increasing amounts of our cells enter into a state known as senescence. Normally, these cells destroy themselves by a self-destruct process known as apoptosis and are disposed of by the immune system. Unfortunately, as we age, increasing numbers of these cells evade apoptosis and linger in the body.

These senescent cells do not divide or support the tissues of which they are a part; instead, they emit a range of harmful chemical signals. Their presence causes many problems, including impairing tissue repair and increasing inflammation, and is linked with the progression of osteoarthritis[1-2], atherosclerosis[3], cancer[4] and other age-related diseases.







As if that was not bad enough, the harmful signals created by senescent cells can also encourage other nearby cells to enter the same senescent state.

So what is the solution?

It has long been suggested that removing these problem cells could be a way to prevent or delay age-related diseases, and, indeed, positive results have been shown in mouse studies[5-7]. Therapies that remove senescent cells are commonly known as senolytics.

SENS Research Foundation members were some of the earliest proponents of removing senescent cells to promote tissue regeneration and to reduce inflammation. Other researchers have, in the years since then, begun to support this idea, with the key 2013 paper Hallmarks of Aging supporting the same approach[8]. This is important, as the paper is widely supported in academia and has likely helped catalyze interest in the approach.

A new Senolytics review







Today, a new review was published by the Mayo Clinic team led by Dr. James Kirkland, one of the pioneers of senescent cell removal therapies known as senolytics[9]. Like a number of other recent reviews on the topic, this publication discusses how removing senescent cells has the potential to change medicine radically in the near future. Dr. Kirkland is very keen to speed up the development and arrival of senolytic therapies, as recent comments show.

“The emerging repertoire of senolytic drugs shows that they are having an impact on a huge range of diseases,” says Dr. Kirkland. “Our goal is to achieve the same success in humans as we have in preclinical animal models in efforts to prevent or delay the conditions associated with aging.” Source: Mayo Clinic

Conclusion

As we can see in this review, the modern concept of treating the underlying causes of age-related diseases represents a considerable shift in thinking away from the traditional approach of treating the consequences rather than the cause. It is great to see that the concept of repair-based approaches to age-related diseases is really catching on in the mainstream.

Interest in senolytics has been ignited in the last year or so, with a number of groups working on the approach in different ways. The leader of the pack is Unity Biotechnology, which is already entering human clinical trials of senolytic drugs this year.

Now if Mayo Clinic proceeds with its own clinical trials, this could only be a good thing, as diversity in approaches means that we can find the best solutions sooner. As companies like Oisin Biotechnologies and others are also hot on the heels of Unity, we can probably be reasonably confident that this technology could be available in the next few years once it passes through the clinical trial process.







Assuming all goes well, this will be a true rejuvenation technology that directly addresses one of the reasons we age and suffer from the diseases of old age. Perhaps once senolytics is finally here, the public will begin to appreciate that they actually have a choice when it comes to aging.

Will resistance to the idea of doing something about aging persist, or will the public be keen to use therapies that help them stay healthy as they age? We rather suspect that the latter will be the case and that it may be the first step to changing how we look at aging forever.

Literature

[1] Jeon, O. H., Kim, C., Laberge, R. M., Demaria, M., Rathod, S., Vasserot, A. P., … & Baker, D. J. (2017). Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nature medicine, 23(6), 775-781.

[2] Xu, M., Bradley, E. W., Weivoda, M. M., Hwang, S. M., Pirtskhalava, T., Decklever, T., … & Lowe, V. (2016). Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, glw154.







[3] Childs, B. G., Baker, D. J., Wijshake, T., Conover, C. A., Campisi, J., & van Deursen, J. M. (2016). Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science, 354(6311), 472-477.

[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, 99–118.

[5] Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., Van De Sluis, B., … & van Deursen, J. M. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 479(7372), 232-236.

[6] Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … & O’Hara, S. P. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging cell, 14(4), 644-658.

[7] Roos, C. M., Zhang, B., Palmer, A. K., Ogrodnik, M. B., Pirtskhalava, T., Thalji, N. M., … & Zhu, Y. (2016). Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging cell.







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

[9] Kirkland.J, Tchkonia.T, Zhu,Y, Niedernhofer.L, & Robbins.D (2017) The Clinical Potential of Senolytic Drugs. Journal of the American Geriatrics Society. DOI: 10.1111/jgs.14969.