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Headlines about miracle pills that slow ageing can spark excitement, but they often outpace the science. Among these, senolytic supplements have gained serious traction in longevity circles. Promising to clear out “zombie cells” that contribute to ageing and chronic disease, compounds like fisetin, quercetin, and curcumin are touted as the next big thing in health optimisation.
But are the benefits backed by research, or mostly driven by anecdotes? In this article, we explore the science behind key senolytics and provide insights into the current state of research and its future direction, with a focus on ongoing clinical trials investigating these compounds in ageing and beyond.
What are Senolytics?
Senescence is a process in which cells stop dividing. Many mechanisms are believed to cause this effect, including damage to DNA, which may be linked to cancer development. Often these cells are destroyed in a natural process by the body, but can accumulate over time. Recently, senescent cells (i.e., cells that have stopped dividing) have been thought to contribute to aging and to certain diseases1.
These developments have led to the idea of using treatments that specifically target and eliminate senescent cells. The term senolytics refers to agents that destroy senescent cells by causing them to break down and die1. There are several reported senolytics, including fisetin, quercetin, and dasatinib in combination, curcumin, and piperlongumine.
Fisetin
Fisetin is a naturally occurring compound found in different fruits and vegetables and has received attention as a potential senolytic agent without affecting non-senescent cells2.
Fact
- Shown to reduce senescent cell burden and extend lifespan in mouse studies
- Shown to kill some types of senescent human cells grown in a laboratory environment
- May have neuroprotective, cardioprotective, and anti-inflammatory effects
- Currently being trialled in human studies2
Fiction
- Dosing protocols (e.g., 20 mg/kg over two days monthly) are not backed by large-scale trials yet
- Human bioavailability is unclear, and absorption may be poor, which has the potential to limit its usability in the clinic2
Current Clinical Trials
Robust clinical data are currently lacking, but fisetin is being investigated to help manage a diverse set of diseases, including many associated with ageing2:
- Carpal Tunnel Syndrome
- Osteoarthritis
- Depression
- Obesity
- Frailty in older adults and cancer survivors
- Glaucoma
- Arterial stiffness
Quercetin + Dasatinib – The Original Senolytic Duo
Quercetin is a compound found in a variety of vegetables, fruits, and plants3. Dasatinib is a pharmaceutical compound used to treat specific types of blood cancer4.
Fact
- This is the first combo identified with senolytic activity in 20155
- Human pilot studies for idiopathic pulmonary fibrosis show a reduction in senescence biomarkers6
- May lead to improved endurance and speed in animal studies7
- Caused a decrease in senescence markers in patients with kidney disease8
Fiction
- The combination of dasatinib and quercetin has been shown in large-scale human trials to slow the signs of ageing.
Current Clinical Trials
So far, evidence on the effects of dasatinib and quercetin comes mainly from small pilot studies. However, further research is underway to better define the potential of this combination for treating various conditions, including some linked to ageing:
- Alzheimer’s disease9
- Skeletal health10
- Fibrotic non-alcoholic fatty liver disease11
- Accelerated ageing in mental disorders12
Curcumin
Curcumin is a bright yellow compound produced by a plant species called Curcuma longa, which is a member of the ginger family of plants13.
Fact
- Curcumin has been the subject of numerous clinical trials, though few of these have assessed ageing-associated factors14
- There are several preclinical and clinical studies demonstrating the anti-inflammatory effects of curcumin supplementation14,15
- It has been shown in preclinical studies to be potentially beneficial for combating Parkinson's disease16
- A curcumin formulation has improved the physical ability of elderly adults in a human trial17
Fiction
- Curcumin is not a true senolytic. It modulates inflammation but doesn’t kill senescent cells18
- All curcumin formulations have low absorption and poor bioavailability19
Current Clinical Trials
Clinical trials for curcumin supplementation have been increasing over the past decades as interest grows in its ability to impact the management and treatment of different conditions14.
Current clinical trials underway include:
- Preventing gastric cancer20
- Reducing joint pain in breast cancer survivors21
Piperlongumine
Piperlongumine is a compound found in the long pepper plant. It has been used in traditional Chinese medicine and has been shown to have senolytic effects22,23.
Fact
- Shows senolytic effects in lab-grown cells and in mice when combined with other compounds23
- May work by increasing oxidative stress in senescent cells, triggering their death24
Fiction
- It has been shown to be effective at reducing signs of ageing in clinical trials.
Current Clinical Trials
Piperlongumine has shown promise as a potential tool in treating cancer, particularly in making cancer cells more sensitive to other treatments25. However, these studies are limited to laboratory cells and mouse studies where piperlongumine has been shown to slow the progression of aggressive brain tumours26.
Nevertheless, at the time of writing, there are currently no clinical trials investigating piperlongumine as a treatment for any condition, including those related to ageing.
Conclusion
Senolytic supplements are a growing part of the longevity conversation, but the evidence is still catching up to the hype. While fisetin and quercetin-based therapies show promise in lab settings, few have made it to large-scale human trials. Rather than relying on generic claims, it's crucial to personalise your approach and examine the effectiveness of senolytic compounds, including bloodwork, wearables, and imaging tools like MRI. Track your progress. Understand your data. Because ultimately, ageing is individual. What works for someone else may not work for you, and that’s okay. The key is to stay curious, cautious, and evidence-led.
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