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As we age, our bodies accumulate increasing numbers of damaged or dysfunctional cells known as senescent cells. Unlike healthy cells which contribute to tissue function, senescent cells have stopped dividing but resist dying off. Instead, they linger and secrete an array of inflammatory molecules, growth factors, and proteases - a phenomenon known as the senescence-associated secretory phenotype (SASP) (Tchkonia & Kirkland, 2018). Over time, the toxic effects of senescent cells and the SASP are thought to be key drivers of aging and age-related diseases.
In recent years, scientists have been exploring a new class of drugs known as senolytics, which selectively eliminate senescent cells while leaving healthy cells unharmed. By clearing senescent cells from the body, the goal is to reduce inflammation, improve tissue function, and ultimately slow or reverse certain aspects of aging. Studies in animal models have shown that administration of senolytics can extend lifespan, reverse age-related declines in physical function, and delay the onset of age-related diseases like osteoarthritis, cardiovascular disease, and Alzheimer's (Xu et al., 2018).
One of the most promising senolytic drugs is a combination of dasatinib (a chemotherapy medication) and quercetin (a plant flavonoid). This duo was shown to selectively eliminate senescent cells and improve health in aged mice, extending their lifespan by 36% (Xu et al., 2018). Other potential senolytics under investigation include fisetin (a flavonoid found in fruits and vegetables), navitoclax (a cancer drug), and FOXO4-DRI (a peptide that disrupts the interaction between the FOXO4 protein and p53 in senescent cells).
While these early results are exciting, more research is needed to determine the safety and efficacy of senolytics in humans. The first human trials of dasatinib and quercetin are currently underway in patients with age-related conditions like chronic kidney disease, osteoarthritis, and Alzheimer's (Justice et al., 2019). If these studies demonstrate positive results, senolytics could become a powerful new tool in the fight against aging and age-related diseases.
Of course, it's important to remember that senolytics are just one piece of the anti-aging puzzle. A comprehensive approach to healthy aging should also include lifestyle factors like a nutritious diet, regular exercise, stress management, and social engagement. By combining these proven strategies with promising new therapies like senolytics, we may be able to not just extend lifespan but also improve healthspan - the years we spend in good health, free of chronic disease and disability. As research in this exciting field continues to evolve, the future of anti-aging medicine looks brighter than ever before.
References:
Justice, J. N., Nambiar, A. M., Tchkonia, T., LeBrasseur, N. K., Pascual, R., Hashmi, S. K., Prata, L., Masternak, M. M., Kritchevsky, S. B., Musi, N., & Kirkland, J. L. (2019). Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine, 40, 554–563. https://doi.org/10.1016/j.ebiom.2018.12.052
Tchkonia, T., & Kirkland, J. L. (2018). Aging, cell senescence, and chronic disease: Emerging therapeutic strategies. JAMA, 320(13), 1319–1320. https://doi.org/10.1001/jama.2018.12440
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., Onken, J. L., Johnson, K. O., Verzosa, G. C., Langhi, L., Weigl, M., Giorgadze, N., LeBrasseur, N. K., Miller, J. D., Jurk, D., … Kirkland, J. L. (2018). Senolytics improve physical function and increase lifespan in old age. Nature Medicine, 24(8), 1246–1256. https://doi.org/10.1038/s41591-018-0092-9