The Cutting Edge of Senolytics: New Developments in Removing Harmful Senescent Cells
Senolytics are emerging as a promising anti-aging therapy. By selectively removing senescent cells that accumulate with age, senolytics aim to prevent or treat age-related diseases and extend healthspan. Recent studies have demonstrated senolytics can improve health in old mice and clinical trials show potential in humans. Here’s an overview of the latest senolytics news and what it could mean for the future.
Senescent Cell Burden Contributes to Obesity and Accelerated Aging
A pre-print study
found that the senolytic navitoclax extended lifespan and reduced weight in obese mice. Mice treated with navitoclax lived 16.7% longer and had less senescent cell burden in their livers compared to untreated obese mice. The findings suggest clearing senescent cells can counter obesity-accelerated aging.
Other studies have connected high senescent cell burden to obesity. Obese mice and humans have more senescent cells, which secrete inflammatory factors contributing to insulin resistance. Weight loss in obese individuals reduces senescent cell burden. Together, these findings indicate senescent cells drive obesity-related diseases.
By removing senescent cells, navitoclax broke the cycle of inflammation and insulin resistance, allowing treated mice to live longer. The late-life weight loss further suggests clearing senescent cells has anti-obesity effects. Since obesity and sedentary lifestyles are rising, senolytics could effectively treat diseases of aging.
Senolytic Therapy Alleviates Alzheimer’s Disease in Mice
Exciting research presented at the 2022 Alzheimer’s Association International Conference demonstrated senolytic drugs may alleviate Alzheimer’s disease (AD). The phase 1 clinical trial
used dasatinib and quercetin (D+Q) to reduce senescent cells in people with AD.
While the trial was small, D+Q showed safety and biological effects. Participants had reduced senescent cell burden after treatment based on their cerebrospinal fluid biomarkers. They also had lower amyloid beta plaques detected by PET imaging. Beyond biomarkers, the participants’ cognition stabilized over the 9 month trial.
This provides initial human evidence that targeting senescent cells may alleviate AD pathology and symptoms. Previous mouse studies found D+Q reduced tau pathology, inflammation, and cognitive deficits. Larger randomized control trials are needed to fully evaluate D+Q for AD. But the mounting evidence continues to support senescent cells contribute to neurodegeneration.
Senolytics Improve Health and Extend Lifespan in Mice
this year showed senolytics can robustly extend healthspan and lifespan in naturally aged mice. Using D+Q, treated 24-month old mice lived 36% longer and stayed healthier compared to untreated mice.
Remarkably, late-life treatment provided similar benefits as lifelong treatment. Old mice given D+Q from 22 to 24 months had improved physical function, reduced osteoporosis and cataracts, and lived 42% longer. This demonstrates senolytics can rapidly improve health, even when initiated late in life.
Analyzing the mice’s blood, D+Q broadly reduced inflammatory cytokines and hormones dysregulated with aging. This systemic rejuvenation and lifespan extension proves clearing senescent cells can reverse aging decline. It provides hope that senolytics may achieve similar benefits in aging humans.
Ongoing Challenges for Senolytic Therapies
While promising, questions remain around the efficacy and safety of senolytics. Different compounds, doses, and treatment regimens make it difficult to compare senolytic effects between studies. Additional research is needed to optimize treatment protocols.
There are also concerns around off-target effects, as most senolytic drugs were originally chemotherapy agents. Their toxicity led to side effects in some human trials. Developing more specific senolytic compounds could improve safety and avoid unintended impacts.
Lastly, some failed attempts to replicate senolytic benefits in mice raise uncertainty around their reliability. For example, the lifespan extension for fisetin wasn’t reproduced in follow-up studies. This exemplifies the need for rigorous, reproducible animal research before human testing.
The Future of Senolytics
Despite limitations, the upside of senolytics makes further research extremely promising. Already, over a dozen clinical trials are underway exploring senolytic therapies for conditions like diabetes, kidney dysfunction, pulmonary fibrosis and more.
As an analogy, antibiotics don’t perfectly discriminate between bacterial and human cells, yet are invaluable medicines. Similarly, even imperfect senolytics that preferentially clear senescent cells could be transformative. Senescent cell burden impairs tissue repair and function – alleviating this could dramatically improve health in later life.
While realizing senolytics’ full anti-aging potential may take years, their advantages make it an exciting goal worth pursuing. With continued progress, senolytics may soon shift to treating illnesses to instead preventing age-related decline.
Emerging senolytic research continues to demonstrate removing senescent cells counteracts aging processes and age-related diseases. Mouse studies show clearing senescent cells can extend lifespan, reverse frailty, and alleviate obesity. Early human trials provide hope senolytics may treat Alzheimer’s disease.
While questions remain around optimizing senolytic compounds and treatment regimens, their health benefits warrant continued research. Overcoming limitations to selectively eliminate harmful senescent cells could enable senolytics to extend human healthspan and longevity.