A Look into Senolytic Therapies for Longevity

With a focus on extending and improving the human lifespan, the medical community continues to explore potential avenues in longevity. One such development has directed increased attention to the practice of senolytics – or, the process of flushing senescent cells from the body to discard harmful proteins. Senescent cells are malfunctioning, aged cells which can trigger inflammation and dysfunction, developed in response to disease, injury, or cancerous formations. 

These cells can remain in the body, contributing to the development of many diseases and features of aging, such as heart disease, dementia, osteoporosis, and lung disease. Removing senescent cells from mice was found to alleviate insulin resistance, cell dysfunction, and ameliorate other complications in cases of kidney failure and disease.

As an emerging strategy in the anti-aging sphere, senolytics still lack a sufficient body of research. Although prior animal-based studies concluded successful results of senolytic therapy, there is no direct demonstration of success in peer-reviewed human clinical trials to date. Recently, the Mayo Clinic revealed the result of an early human study aimed at confirming the effects of decreasing senescent cells in the body as found in animal-based studies.

Preliminary Research Reveals Benefit for DKD Patients

Conducted by a team of Mayo Clinic researchers, the Phase I trial tested a senolytic regimen comprised of the cancer drug dasatinib (Sprycel) and plant-derived quercetin in nine patients with diabetes-related chronic kidney disease (DKD). Patients given the medication combination for a total of three days, after which the treatment was stopped. 

Despite being completely eliminated from the system within a few days, the drugs and their effects appeared to last. According to study authors, the key markers of senescent cell burden decreased in both adipose tissue and skin biopsied from subjects 11 days after treatment completion, as were key circulating SASP factors compared with pre-treatment levels. The results remained persistent across measures – including blood, skin, and fat tissue analysis of senescent cell abundance.

Implications of Senolytic Therapy Potential

Decreasing senescent cell numbers in two human tissues brings promise of growing understanding of senolytics and credibility of animal-based senolytic study results – which may be translatable to humans. Illustrating the mechanism of action discovered in prior research, the study implicates the potential of short-term dasatinib and quercetin treatment to improve physical functioning in patients with diabetes-related chronic kidney disease.

Senolytic therapies may provide efficacious treatment opportunities for an array of age-related diseases – chronic kidney disease, cancer, and neurodegenerative disorders – which place a significant burden on the healthcare system. Current knowledge suggests that senolytics may delay, prevent, or treat Alzheimer’s and Parkinson’s disease while enhancing longevity and improving the quality of later life.

However, the field is still new. As one of the first emerging clinical trials being reported, the latest study highlights the preliminary nature of its results. Fewer than 150 subjects have been treated, knowledge of adverse effects and potential long-term health repercussions is still growing and may further influence the development of senolytic therapy. Researchers caution against implementing senolytics into the practice setting until more information is obtained from additional clinical trials. Nonetheless, the study represents the first preliminary evidence in the promising field of senolytic therapies, verifying the potential benefit of their use on the human body.