The Promise of Senolytics: Targeting Aging at the Cellular Level

As the search for effective anti-aging therapies continues, one of the most promising developments in recent years has been the emergence of senolytics—a class of drugs designed to target and eliminate senescent cells. These so-called “zombie cells” accumulate with age and contribute to many age-related diseases, including cancer, cardiovascular disease, and neurodegeneration. By clearing these harmful cells from the body, senolytics offer the potential to extend healthspan, reduce chronic disease risk, and improve overall quality of life. Early clinical trials in humans are already yielding encouraging results, suggesting that senolytics may be the key to unlocking longer, healthier lives.

What Are Senescent Cells?

Senescent cells are damaged or aged cells that have stopped dividing but remain metabolically active. Recent studies suggest they may in fact be more metabolic active than normal cells. Rather than dying through the normal process of apoptosis (programmed cell death), these cells persist in the body, releasing harmful inflammatory signals and contributing to tissue dysfunction. While senescence is a protective mechanism to prevent damaged cells from becoming cancerous, the accumulation of these cells over time is linked to the development of several chronic diseases, including osteoarthritis, cardiovascular disease, diabetes, and dementia.

 As we age, the immune system becomes less effective at clearing senescent cells, leading to their buildup in tissues throughout the body. This accumulation of senescent cells not only accelerates the aging process but also creates a toxic environment that promotes the progression of age-related diseases.

 The negative effects of zombie cells Is mainly driven by the SASP - Senescence Associated Secretory Phenomena - which affects surrounding cells and contributes to body wide inflammation.

How Senolytics Work

 Senolytics are drugs that selectively target and destroy senescent cells without harming healthy, functioning cells. By clearing out these dysfunctional cells, senolytics can help restore tissue function, reduce inflammation, and potentially reverse aspects of the aging process.

 The first generation of senolytic drugs includes compounds such as dasatinib (a cancer drug) and **quercetin** (a natural flavonoid found in fruits and vegetables). These drugs have been shown to selectively kill senescent cells in animal models, improving physical function, extending lifespan, and reducing the risk of diseases such as osteoporosis, heart disease, and frailty. Other compounds being explored include fisetin, another natural flavonoid, and navitoclax, a drug that targets anti-apoptotic pathways in senescent cells.

Human Clinical Trials: A Glimpse into the Future

 Although most of the research on senolytics has been conducted in animals, several early-phase human clinical trials have shown promising results, suggesting that senolytic therapies could soon become a viable option for preventing or treating age-related diseases in humans.

 1. Mayo Clinic Senolytic Trials: One of the most significant clinical trials was conducted by researchers at the Mayo Clinic, testing the combination of dasatinib and quercetin in older adults with idiopathic pulmonary fibrosis (IPF), a chronic lung disease linked to senescence. The results were encouraging: after just three weeks of treatment, participants showed significant improvements in physical function, including walking speed and grip strength. Importantly, there were no serious adverse effects, supporting the potential safety of senolytic treatments in humans .

 2. UNITY Biotechnology’s Senolytic Trials: UNITY Biotechnology, a company focused on developing senolytic therapies, has conducted clinical trials to test the safety and efficacy of senolytics in patients with osteoarthritis. While the Phase II trial results were mixed, with no significant improvement in pain reduction, the treatment did demonstrate a reduction in markers of cartilage degradation, suggesting that senolytics may have a role in slowing disease progression . This study provided important safety data, showing that short-term administration of senolytics was well tolerated in older adults.

 3. Fisetin Trials: Fisetin, a natural senolytic compound found in strawberries and other fruits, has also been tested in small human trials. Early research suggests that fisetin can reduce markers of inflammation and improve tissue health in older adults. Ongoing studies are exploring its role in reducing frailty and improving cognitive function in older populations, with preliminary results suggesting it could be a safe, over-the-counter option for targeting senescent cells .

The Potential Impact of Senolytics on Healthspan

 By reducing the burden of senescent cells, senolytics offer the potential to delay or even reverse the onset of multiple age-related diseases. This approach is fundamentally different from traditional treatments, which often target single diseases or symptoms. Senolytics, by contrast, address one of the root causes of aging itself—cellular senescence—making them a potentially transformative intervention for extending healthspan and lifespan. Cellular senescence plays key roles in cardiovascular disease, neurodegeneration, musculoskeletal ageing, cancer and the ageing of our immune system, immunosenescence.

 Addressing Safety and Long-Term Effects

 While the potential benefits of senolytics are clear, the usual precautions surrounding long term and unanticipated side effects need to be considered. As with any new therapy, it is crucial to understand both the short- and long-term risks.

 So far, clinical trials have shown that senolytics can be administered safely in the short term, with few serious adverse events reported. However, long-term data are still needed to determine whether senolytics can be used continuously or intermittently over time without causing harm. The selective nature of these drugs—targeting only senescent cells while sparing healthy ones—helps mitigate the risk of widespread toxicity.

Conclusion: The Future of Senolytics

 The early results from human trials, combined with the wealth of data from animal studies, suggest that senolytics could represent a major breakthrough in the field of anti-aging medicine. By targeting and eliminating senescent cells, these drugs have the potential to delay or prevent a wide range of age-related diseases, extending both healthspan and lifespan.

 As more clinical trials are conducted and new senolytic compounds are developed, we are likely to see senolytics become a key component of preventative health strategies for aging populations. While challenges remain—particularly regarding long-term safety and efficacy—senolytics offer a glimpse into a future where ageing itself is treated as a modifiable risk factor, rather than an inevitable decline.

References

1. Justice, J.N., et al. "Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study." *EBioMedicine*, 2019.

2. UNITY Biotechnology. "UNITY Biotechnology Reports Results of Phase 2 Study of UBX0101 in Patients with Osteoarthritis of the Knee." *UNITY Press Release*, 2020.

3. Yousefzadeh, M.J., et al. "Fisetin is a senotherapeutic that extends health and lifespan." *EBioMedicine*, 2018.

4. Xu, M., et al. "Senolytics improve physical function and increase lifespan in old age." *Nature Medicine*, 2018.

 Copyright Dr Christopher Maclay 2024. All rights reserved.

Disclaimer: This information is for educational purposes only, it does not constitute medical advice. Please consult with your health care practitioner for personalised medical advice.