Senolytics in Food: Potential Benefits for Healthy Aging

Aging leads to the accumulation of senescent cells, which stop dividing but remain active, releasing inflammatory signals that contribute to tissue dysfunction. Researchers are exploring ways to remove these cells to support healthier aging, with senolytics—compounds that selectively eliminate senescent cells—emerging as a promising approach.

Certain foods contain natural compounds with potential senolytic properties, raising interest in dietary strategies for longevity. Scientists are investigating whether specific food-derived molecules can help clear harmful senescent cells and improve overall health.

Physiology Of Senescent Cells

Cellular senescence occurs when cells permanently cease dividing in response to stressors like DNA damage, oxidative stress, and telomere shortening. Initially, this process prevents the proliferation of damaged cells, but over time, the accumulation of senescent cells contributes to aging and disease. These cells resist apoptosis, the programmed cell death that typically removes dysfunctional cells, leading to their persistence in tissues where they secrete a mix of bioactive molecules known as the senescence-associated secretory phenotype (SASP).

The SASP includes pro-inflammatory cytokines, chemokines, growth factors, and enzymes that degrade the extracellular matrix. While some SASP components aid in wound healing, their chronic presence promotes inflammation and tissue dysfunction, exacerbating conditions like osteoarthritis, atherosclerosis, and neurodegenerative diseases.

Senescent cells also impair tissue regeneration by disrupting stem cell function, reducing the body’s ability to replace damaged or aging cells. In organs with high cellular turnover, such as the skin and liver, this decline in regenerative capacity contributes to age-related deterioration. Studies in aged mice have shown that eliminating senescent cells improves tissue function and extends lifespan, highlighting their role in aging.

Compounds In Food That Target Senescence

Certain bioactive compounds in food may help reduce senescent cell burden by influencing pathways involved in their survival and clearance. Among the most studied are polyphenols, flavonoids, and isoflavones, which exhibit properties that could support healthier aging.

Polyphenols

Polyphenols are plant-derived compounds with antioxidant and anti-inflammatory effects. Some, like quercetin and fisetin, have demonstrated senolytic activity by inducing apoptosis in senescent cells. A 2018 study in EBioMedicine found that fisetin, a flavonol in strawberries, apples, and onions, reduced senescent cell burden in aged mice, improving tissue function and extending lifespan. This effect is linked to the inhibition of pro-survival pathways, such as those regulated by BCL-2 family proteins.

Resveratrol, found in grapes and red wine, influences cellular aging by activating sirtuins, proteins involved in stress resistance and longevity. While not a direct senolytic, resveratrol enhances autophagy and mitochondrial function, potentially mitigating the harmful effects of senescent cells.

Flavonoids

Flavonoids, a subclass of polyphenols, are found in fruits, vegetables, and tea. Quercetin, present in capers, onions, and citrus fruits, has been studied as a senolytic, particularly in combination with dasatinib, a tyrosine kinase inhibitor. A 2015 Nature Medicine study found that this combination selectively eliminated senescent cells in aged mice, improving physical function and reducing markers of aging.

Epigallocatechin gallate (EGCG), the primary catechin in green tea, modulates oxidative stress and inflammation, factors contributing to senescence. While not classified as a senolytic, EGCG influences pathways such as AMPK activation and NRF2 signaling, which regulate antioxidant defenses and metabolic balance.

Isoflavones

Isoflavones, found in soy products, affect senescence-related pathways. Genistein, a predominant isoflavone in soybeans, influences oxidative stress and inflammation. Research in The Journals of Gerontology (2020) suggests that genistein may reduce senescence markers in endothelial cells, potentially supporting vascular health.

Daidzein, another isoflavone, has been studied for its effects on metabolism and longevity pathways. Some findings suggest it activates sirtuins and modulates autophagy, processes that may influence the accumulation of senescent cells. While not direct senolytics, isoflavones help regulate cellular stress and inflammation, making them relevant in aging research.

Research On Food-Based Senolytic Activity

Scientists are investigating food-derived senolytics for their ability to selectively eliminate senescent cells while preserving healthy tissue. This research has gained momentum as dietary interventions may complement pharmacological approaches to aging.

Polyphenols like fisetin disrupt pro-survival mechanisms that senescent cells rely on. A 2022 clinical trial in The Lancet Healthy Longevity found that fisetin supplementation in older adults reduced circulating senescence biomarkers, aligning with prior animal studies where fisetin improved tissue function and extended lifespan. Researchers believe fisetin’s ability to inhibit the PI3K/AKT and mTOR pathways contributes to its effectiveness.

Quercetin has also been studied in combination with dasatinib for age-related diseases like idiopathic pulmonary fibrosis (IPF), a condition linked to senescent cell accumulation. A 2019 EBioMedicine study reported that participants receiving quercetin and dasatinib experienced improved physical function and reduced inflammation. While dasatinib is a drug, quercetin’s presence in foods like apples and onions raises the possibility of dietary strategies influencing senescence pathways.

Green tea catechins, particularly EGCG, have been explored for their role in reducing senescence-induced inflammation. A 2021 study in The Journal of Nutritional Biochemistry found that EGCG supplementation in aged rodents reduced senescence-associated β-galactosidase activity, a marker of cellular senescence. Though not a direct senolytic, EGCG may create an environment less conducive to senescent cell persistence.