As you go about your life, something happens inside your body that you probably aren’t aware of.
When your cells age, they become dysfunctional or senescent. Normally, as a young person, your old cells die off through a process called apoptosis.
But with age this process starts to break down. The old cells don’t die off.
They start building up and emit toxic compounds known as senescence-associated secretory phenotype, or SASP, that cause long term inflammation that leads to disease (1).
Many diseases such as diabetes, stroke, cancer and osteoarthritis can be caused by senescent cells (2).
If you haven’t heard about this, that’s okay. Many people haven’t. This field of study, known as senolytics, seeks to discover how to remove senescent cells.
Senolytics are compounds that eliminate senescent cells by reactivating apoptosis.
Improved physical function and health, as well as increased lifespan were seen in mice given senolytic compounds (11).
Atherosclerosis was halted and reversed in mice given senolytic agents (12).
The good news is that senolytics are showing promise, and they are available to you right now.
Senolytics promote a longer, healthier life
So what are these compounds that can help you remove senescent cells?
A groundbreaking study done at Mayo Clinic and Scripps Research Institute demonstrated that senescent cells can be removed by certain agents (3). Using the cancer drug dasatinib with quercetin, they were able to reduce the senescent cell burden of people with diabetes and chronic kidney disease from ages 55 to 79.
Quercetin is a flavonoid found in fruits and vegetables such as capers, red onions, fennel and kale.
The anti-inflammatory and antioxidant effects of quercetin may also help with controlling blood sugar and preventing cancer and heart disease.
Other plant-based agents known as theaflavins, from black tea, have also been found to have senolytic properties(4,5,6).
Fortunately, naturally occurring flavonoids quercetin and black tea theaflavins don’t have the side effects of the drug dasatinib.
Fisetin, a plant flavonoid found in strawberries, cucumbers, onions, persimmons and apples, has been demonstrated to be a senolytic agent.
Stawberries have the highest content of fisetin of any food. Fisetin has also been shown to be twice as effective as quercetin (9).
Unfortunately, fisetin is quickly digested and very little enters the bloodstream. But scientists have come up with a way to avoid this problem in supplement form by combining it with Fenugreek compounds.
A published study by Yousefzadeh et al tested 10 senolytic compounds and found fisetin to be the most effective (10).
Fisetin has also been shown to benefit people who have had a stroke by extending their therapy window (13).
Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan. Fisetin has been shown to increase the lifespan of mice by 10%.
Another compound found to have senolytic properties is the flavonoid apigenin. It’s found in vegetables and fruits. Parsley, celery, celeriac and chamomile tea are abundant sources of apigenin.
One study was able to suppress SASP in breast cancer cells using apigenin (14).
In addition to being a senolytic, apigenin has been shown to cause cancer cells to stop replicating and die off(15,16,17,18).
How to use senolytics for a longer, healthier life
The effectiveness of senolytics in food hasn’t been determined yet. You may want to consider taking a senolytic supplement.
This doesn’t mean you should cut back on, or stop eating fruits and vegetables.
Fortunately, quercetin, fisetin, apigenin and black tea theaflavins are all available in supplement form.
Another advantage to getting senolytics in the supplement form is that they are more focused and formulated for special delivery.
According to the Life Extension Foundation, quercetin encased in a plant-derived phytosome makes it 50 times more bioavailable than standard quercetin.
Researchers have been trying to determine the best frequency for using senolytics: continual or intermittent.
Nonsenescent cells may be adversely affected by senolytic agents given in a continual high dose (7).
The Mayo Clinic study, as well as other researchers, have discovered that intermittent use of senolytics seems to be a better approach than continual therapeutics (7, 8).
The four senolytics to remember are fisetin, quercetin, theaflavins and apigenin.
Although many published studies show that flavonoid senolytics are safe, it’s always a good idea to make your physician aware of what you’re taking.
If you decide to take a senolytic supplement, as always, don’t exceed the recommended dose.
Taking a senolytic supplement once a week may be a promising strategy for eliminating senescent cells and promoting a longer, healthier life.
- Dodig S, Cepelak I, Pavic I. Hallmarks of senescence and aging. Biochem Med (Zagreb). 2019 Oct 15;29(3):030501.
- Zhu Y, Armstrong JL, Tchkonia T, et al. Cellular senescence and the senescent secretory phenotype in age-related chronic diseases. Curr Opin Clin Nutr Metab Care. 2014 Jul;17(4):324-8.
- Hickson L.J. et al. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine.(In Press).
- Noberini R, Koolpe M, Lamberto I, et al. Inhibition of Eph receptor-ephrin ligand interaction by tea polyphenols. Pharmacol Res. 2012;66(4):363-73.
- Noberini R, Lamberto I, Pasquale EB. Targeting Eph receptors with peptides and small molecules: progress and challenges. Semin Cell Dev Biol. 2012;23(1):51-7.
- Ting PY, Damoiseaux R, Titz B, et al. Identification of small molecules that disrupt signaling between ABL and its positive regulator RIN1. PLoS One. 2015;10(3):e0121833.
- Kirkland JL, Tchkonia T. Cellular Senescence: A Translational Perspective. 2017;21:21-8.
- RC, Bin Z, K. PA, et al. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell. 2016;15(5):973-7.
- Wyld L, Bellantuono I, Tchkonia T, Danson S, Kirkland JL (2020). Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies. Cancers. 12 (8): e2134. doi:3390/cancers12082134.
- Xu M., Pirtskhalava T., Farr J.N., Weigand B.M., Palmer A.K., Weivoda M.M. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24:1246–1256. doi: 10.1038/s41591-018-0092-9.
- Childs BG, Baker DJ, Wijshake T, et al. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. 2016 Oct 28;354(6311):472-7.
- Wang L, Cao D, Wu H, et al. Fisetin Prolongs Therapy Window of Brain Ischemic Stroke Using Tissue Plasminogen Activator: A Double-Blind Randomized Placebo-Controlled Clinical Trial. Clin Appl Thromb Hemost. 2019 Jan-Dec;25:1076029619871359.
- Perrott KM, Wiley CD, Desprez PY, et al. Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells. 2017 Apr;39(2):161-73.
- Cardenas H, Arango D, Nicholas C, et al. Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-kappaB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function. Int J Mol Sci. 2016;17(3):323.
- Shukla S, Kanwal R, Shankar E, et al. Apigenin blocks IKKalpha activation and suppresses prostate cancer progression. Oncotarget. 2015;6(31):31216-32.
- Hashemi M, Nouri Long M, Entezari M, et al. Anti-mutagenic and pro-apoptotic effects of apigenin on human chronic lymphocytic leukemia cells. Acta Med Iran. 2010;48(5):283-8.
- King JC, Lu QY, Li G, et al. Evidence for activation of mutated p53 by apigenin in human pancreatic cancer. Biochim Biophys Acta. 2012;1823(2):593-604.