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Fisetin (FIS)

Fisetin is a senolytic that helps to gets rid of the Senescence (zombie) cells that accumulate as we age. Our Fisetin provides 750mg of fisetin per serving (three capsules) take for 5 days each month.
Each capsule contains: 250mg fisetin and supports healthy ageing.
Our products are manufactured and stored in cool, dark and dry environments. This product is suitable for vegans.

60 x 250mg API Capsules

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$59.50 AUD

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$169.50 AUD

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$321.50 AUD

What is Fisetin (API)?

Fisetin is a plant polyphenol and part of the flavonoid group in the flavonol sub-category. Fisetin is a bioflavonoid antioxidant that can help maintain glutathione levels and mitochondrial function in the presence of oxidative stress.

Flavonoids are substances that give fruits and vegetables their bright colors (like yellow, orange and blue) and play a major role in conferring the health benefits that we get from eating more vegetables and fruits.

Fisetin is commonly found in many fruits and vegetables such as apples, persimmons, grapes, kiwis, strawberries, onions and cucumbers.  In fact, the earliest record of isolated fisetin dates back to 1833 taken from the smoke bush (Rhus cotinus), so it has been around for a long time.

Flavonoids from dietary sources are the most sought after because of their safety and feasibility of oral administration. 

What foods contain Fisetin?

It can be found in many common fruits and vegetables, although the amounts can vary considerably.


Amount (ml/g)


Amount (ml/g)

Lotus Root5.8Cucumber0.1
fisetin strawberry

Why Fisetin important to Anti Aging?

Senescence is a process by which a cell ages and permanently stops dividing but does not die.  Over time, large numbers of old (senescent) cells can build up in tissues throughout the body and usually occur over a few months.   Senescent cell production rate increases with age due to accumulation of mutations, telomere damage and other factors triggering cell senescence.   Senescence may play a role in the development of cancer and other diseases. 

Recent studies found fisetin to be the most potent senolytic compound among a group of flavonoids that were tested.

Fisetin is the most potent senolytic and can increase lifespan.  Fisetin has also shown the potential to fight multiple cancers, protect the brain from strokes, reduce inflammation, reduce seizures, support the immune system and fight many other diseases.

Karin O, Agrawal A, Porat Z, et al. Senescent cell turnover slows with age providing an explanation for the Gompertz law. Nat Commun. 2019 Dec 2;10(1):5495.


Senescence is a tumor suppressor mechanism activated in stressed cells to prevent replication of damaged DNA.   Senescent cells (SC) have been demonstrated to play a causal role in driving aging and age-related diseases using genetic and pharmacologic approaches.  

Of the 10 flavonoids tested, fisetin was the most potent senolytic.  Acute or intermittent treatment of progeroid and old mice with fisetin reduced senescence markers in multiple tissues, consistent with a hit-and-run senolytic mechanism.

Fisetin reduced senescence in a subset of cells in murine and human adipose tissue, demonstrating cell-type specificity.  Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan.  The natural product fisetin has senotherapeutic activity in mice and in human tissues.  Late life intervention was sufficient to yield a potent health benefit.  

Because SC take weeks to reaccumulate, senolytics can be administered intermittently - a 'hit-and-run' approach.

In preclinical models, senolytics delay, prevent or alleviate frailty, cancers and cardiovascular, neuropsychiatric, liver, kidney, musculoskeletal, lung, eye, haematological, metabolic and skin disorders as well as complications of organ transplantation, radiation and cancer treatment.

Senescent Cell Removal Declines with Aging

In 3 month old mice, Senescent cells turnover every five days but take 25 days to turnover in 22-month-old mice.  This model predicts a vicious cycle where senescent cells accumulate faster and are degraded (turned over) slower.

At the point of 30% senescent cell load animals often appear to reach tipping point resulting in death.

“Our results suggest that treatments that remove senescent cells can therefore have a double benefit:  an immediate benefit from a reduced senescent cell load, and a longer term benefit from increased senescent cells removal.”

What are the benefits of Fisetin?

Fisetin extends lifespan in various organisms.  Fisetin reduces the amount of senescent cells, which are cells that increase during aging and damage healthy surrounding cells, accelerating the aging process.

Whilst more often used for the above reasons, fisetin has also been shown to reduce depression, boost serotonin levels and boost hair growth.   Fisetin has been shown to remove senescent cells, support reduction of inflammation, support the body in its fight against brain decline and cancer progression.

Getting enough fisetin from our diets is difficult, the most fisetin can be found in strawberries.  One strawberry contains on average less than 2mg of fisetin.  This means to get the same fisetin from your diet as you do from one serving of Restore-U Fisetin, the minimum you would have to eat is 350 strawberries!

1) Preventing Obesity and Diabetes

Obesity leads to a skyrocketing risk of metabolic disorders such as type II diabetes. It also increases the risk for cardiovascular disease, cancer, dementia, and many other disorders.

Preclinical studies show that fisetin appears to act as a kind of “metabolism control switch,” reducing fat cell accumulation and suppressing activation of the protein mTOR, which is linked to weight gain.  In mice fed a high-fat diet, fisetin prevented increase in body weight and accumulation of harmful white fat tissue.15  

Fisetin also helped fight fat accumulation in the livers of animals fed a high-fat diet, a common occurrence with metabolic disease that can compromise liver function and lead to fatty liver disease.35-38  

Fisetin may provide benefits for those already suffering from type II diabetes.   In rodent models of diabetes, fisetin lowers body weight and leads to improved glucose control with lower hemoglobin A1c levels, a marker of blood sugar regulation over time.16,17  

Poorly controlled diabetes often causes disabling or life-threatening complications throughout the body. In mice, fisetin significantly reduces the severity of diabetic complications, including slowing the progression of cataracts, preventing kidney damage, and improving kidney function.16,39  

A human trial of fisetin’s ability to protect kidney function, particularly in diabetes patients, is currently underway.40

2) Cancer

Cancer remains a major public health concern and a significant cause of death worldwide.  Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities.

Dietary flavonoid fisetin has been shown in preclinical studies to inhibit cancer growth through alteration of cell cycle, inducing apoptosis, angiogenesis, invasion, and metastasis without causing any toxicity to normal cells.  Although data from in-vitro and in-vivo studies look convincing, well-designed clinical trials in humans are needed to conclusively determine the efficacy across various cancers.

Fisetin has shown potential in preventing cancer and limiting the growth and spread of existing tumors in preclinical studies.  Among its anti-cancer properties:

  • Fisetin induces apoptosis, or programmed cell death, in cancer, which can facilitate removal of tumor cells.47-50
  • As an anti-inflammatory, fisetin reduces compounds that contribute to chronic inflammation and cancer progression.42-45 In a study of patients with colorectal cancer, fisetin reduced levels of pro-inflammatory mediators.46
  • Fisetin enhances autophagy,51 cellular housekeeping that keeps cells functioning normally. Enhanced autophagy can inhibit cancer cell survival.
  • Fisetin helps prevent angiogenesis, the formation of new blood vessels, in cancer, starving tumor cells of oxygen and glucose.52,53
  • Fisetin helps prevent oxidative damage which can contribute to DNA mutations and cancer development.42,43
  • Fisetin may inhibit cancer cell migration and metastasis, the spread of cancer to a different part of the body.54
3) Cardiac

Myocardial infarction (MI) is a leading cause of death worldwide.  Reperfusion is considered as an optimal therapy following cardiac ischemia.  Fisetin is thus a highly promising candidate drug with clinical potential to protect from ischemic damage following Myocardial infarction (MI) and to overcome ischemia reperfusion injury (IRI).

People who suffer from a stroke are often treated with medication to dissolve the clot blocking blood flow to the brain.  This can save a patient’s life, prevent damage to the brain, and even reverse the symptoms of stroke in some patients.

But ER doctors are working against the clock when treating acute (ischemic) stroke.  The best chances of success occur when treatment begins within three hours of the onset of symptoms.41  Many people suffering a stroke are treated too late and suffer permanent neurological injury (and paralysis).

Studies show that combining clot-dissolving medication with fisetin significantly extends the treatment window.10

Patients receiving fisetin in addition to usual treatment up to five hours after a stroke had neurological outcomes as good as those treated within three hours.  This extension of the therapeutic window means that many stroke victims who would otherwise suffer permanent loss of brain function have a better chance of recovery.

Fisetin has also shown neuroprotective benefits in animal models of Alzheimer’s disease, Amyotrophic Lateral Sclerosis, Parkinson’s disease and other brain pathologies, reducing the severity of disease and improving cognitive function.2,4-9

4) Brain Function

It is becoming increasingly clear that neurological diseases are multi-factorial involving disruptions in multiple cellular systems.   Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin.   Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant.  Fisetin can also activate key neurotrophic factor signaling pathways.   In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products.

5) Anti Inflammatory

Chronic inflammation is a prolonged and dysregulated immune response leading to a wide variety of physiological and pathological conditions such as neurological abnormalities, cardiovascular diseases, diabetes, obesity, pulmonary diseases, immunological diseases, cancers, and other life-threatening conditions.

Therefore, inhibition of persistent inflammation will reduce the risk of inflammation-associated chronic diseases.

6) Anti-Aging Properties

Sirtuin proteins are another anti-aging target.24,25  These cellular protectors are found in all cells in the body, and are vital for keeping cells performing at peak level.

Sirtuin function tends to diminish with age.  But fisetin activates sirtuin function in cells, countering this decline.26-30

In various animal models, sirtuin activation has been shown to extend lifespan significantly.24,25,31,32

Fisetin may protect against aging in other ways:

  • It reduces inflammation, a driver of many chronic illnesses and even of aging itself.2
  • It mimics some of the effects of a calorie-restricted diet, which has been shown to boost resistance to disease and increase lifespan.1,2,29,34
  • It helps prevent oxidative damage that leads to accelerated aging and degenerative disease.33
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Is Fisetin Safe? And what are the side effects of Fiestin?

There is no evidence that fisetin would cause side effects, but no studies in humans have been conducted.   There is no safety data for fisetin supplementation in humans, though no toxicity in animals has been reported.

However, clinical trial data is still quite limited in particular regarding long-term use.  As always, if you do decide to take a fisetin supplement and experience any adverse effects, you should cease taking it immediately and consult your doctor.

Importantly, no adverse effects of fisetin have been reported, even when given at high doses.  Thus, our results suggest that supplementation or even intermittent treatment with this safe, natural product could improve healthy aging, even in elderly individuals.


What dosage do I take?

The amount of fisetin consumed in clinical trials vary greatly, with participants taking doses ranging from 100 milligrams per day to 1,400 milligrams daily.  Recommendations on fisetin supplement labels vary as well, with doses ranging from 100–500 milligrams per day.

There is no safety data for fisetin supplementation in humans, though no toxicity in animals has been reported.  

Two studies in Japanese women suggest an average daily intake of 400-800mg was safe; however, this was conducted from food surveys (Kimira et al, 1998; Arai et al, 2000).


Fisetin is a senotherapeutic that extends health and lifespan.

Fisetin: A Dietary Antioxidant for Health Promotion.

Some aspects of the in vivo neuroprotective capacity of flavonoids: bioavailability and structure-activity relationship.

Fisetin and Its Role in Chronic Diseases.

Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations.

Fisetin provides antidepressant effects by activating the tropomyosin receptor kinase B signal pathway in mice.

The antidepressant-like effect of fisetin involves the serotonergic and noradrenergic system.

Fisetin, a dietary flavonoid, augments the anti-invasive and anti-metastatic potential of sorafenib in melanoma.

Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: findings from 3-D melanoma skin equivalents and computational modelling.

The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways.

Anti-cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies.

Dietary flavonoid fisetin increases abundance of high-molecular-mass hyaluronan conferring resistance to prostate oncogenesis.

Dietary flavonoid fisetin: a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management.

Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity.

Dietary flavonoid fisetin for cancer prevention and treatment.

Fisetin Acts on Multiple Pathways to Reduce the Impact of Age and Disease on CNS Function.

The flavonoid fisetin as an anticancer agent targeting the growth signaling pathways.

Senolytic drugs: from discovery to translation.

  1. Grynkiewicz G, Demchuk OM. New Perspectives for Fisetin. Front Chem. 2019;7:697.
  2. Pal HC, Pearlman RL, Afaq F. Fisetin and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016;928:213-44.
  3. Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. 2018 Oct;36:18-28.
  4. Ahmad A, Ali T, Park HY, et al. Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice. Mol Neurobiol. 2017 Apr;54(3):2269-85.
  5. Alikatte K, Palle S, Rajendra Kumar J, et al. Fisetin Improved Rotenone-Induced Behavioral Deficits, Oxidative Changes, and Mitochondrial Dysfunctions in Rat Model of Parkinson’s Disease. J Diet Suppl. 2020 Jan 29:1-15.
  6. Chen C, Yao L, Cui J, et al. Fisetin Protects against Intracerebral Hemorrhage-Induced Neuroinflammation in Aged Mice. Cerebrovasc Dis . 2018;45(3-4):154-61.
  7. Maher P. Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin. Genes Nutr. 2009 Dec;4(4):297-307.
  8. Maher P, Akaishi T, Abe K. Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory. Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16568-73.
  9. Zhang L, Wang H, Zhou Y, et al. Fisetin alleviates oxidative stress after traumatic brain injury via the Nrf2-ARE pathway. Neurochem Int. 2018 Sep;118:304-13.
  10. 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.
  11. Khan N, Afaq F, Syed DN, et al. Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells. 2008 May;29(5):1049-56.
  12. Li J, Cheng Y, Qu W, et al. Fisetin, a dietary flavonoid, induces cell cycle arrest and apoptosis through activation of p53 and inhibition of NF-kappa B pathways in bladder cancer cells. Basic Clin Pharmacol Toxicol. 2011 Feb;108(2):84-93.
  13. Suh Y, Afaq F, Johnson JJ, et al. A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB-signaling pathways. 2009 Feb;30(2):300-7.
  14. Ying TH, Yang SF, Tsai SJ, et al. Fisetin induces apoptosis in human cervical cancer HeLa cells through ERK1/2-mediated activation of caspase-8-/caspase-3-dependent pathway. Arch Toxicol. 2012 Feb;86(2):263-73.
  15. Jung CH, Kim H, Ahn J, et al. Fisetin regulates obesity by targeting mTORC1 signaling. J Nutr Biochem. 2013 Aug;24(8):1547-54.
  16. Ge C, Xu M, Qin Y, et al. Fisetin supplementation prevents high fat diet-induced diabetic nephropathy by repressing insulin resistance and RIP3-regulated inflammation. Food Funct. 2019 May 22;10(5):2970-85.
  17. Vinayagam R, Xu B. Antidiabetic properties of dietary flavonoids: a cellular mechanism review. Nutr Metab (Lond). 2015;12:60.
  18. A cross over pilot pharmacokinetic study of fisetin 1000mg and formulated fisetin 200mg administered in a single dose to healthy volunteers. Manufacturer’s study (in press for future publication) . 2020.
  19. Dodig S, Cepelak I, Pavic I. Hallmarks of senescence and aging. Biochem Med (Zagreb). 2019 Oct 15;29(3):030501.
  20. Grynkiewicz G, Demchuk OM. New Perspectives for Fisetin. Frontiers in Chemistry. 2019 2019-October-30;7(697).
  21. Pallauf K, Duckstein N, Rimbach G. A literature review of flavonoids and lifespan in model organisms. Proc Nutr Soc. 2017 May;76(2):145-62.
  22. Zhu Y, Doornebal EJ, Pirtskhalava T, et al. New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463. Aging (Albany NY). 2017 Mar 8;9(3): 955-63.
  23. Available at: Accessed June 22, 2020,
  24. Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014 Aug;24(8):464-71.
  25. Johnson S, Imai SI. NAD (+) biosynthesis, aging, and disease. 2018;7:132.
  26. Bai X, Yao L, Ma X, et al. Small Molecules as SIRT Modulators. Mini Rev Med Chem. 2018;18(13):1151-7.
  27. Kim A, Lee W, Yun JM. Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions. Nutr Res Pract. 2017 Oct;11(5):430-4.
  28. Kim SC, Kim YH, Son SW, et al. Fisetin induces Sirt1 expression while inhibiting early adipogenesis in 3T3-L1 cells. Biochem Biophys Res Commun. 2015 Nov 27;467(4):638-44.
  29. Singh S, Singh AK, Garg G, et al. Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration. Life Sci. 2018 Jan 15;193:171-9.
  30. Zheng W, Feng Z, You S, et al. Fisetin inhibits IL-1beta-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice. Int Immunopharmacol. 2017 Apr;45:135-47.
  31. Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018 Mar 6;27(3):529-47.
  32. Watroba M, Dudek I, Skoda M, et al. Sirtuins, epigenetics and longevity. Ageing Res Rev. 2017 Nov;40:11-9.
  33. Naeimi AF, Alizadeh M. Antioxidant properties of the flavonoid fisetin: An updated review of in vivo and in vitro studies. Trends in Food Science & Technology. 2017 2017/12/01/;70:34-44.
  34. Khan N, Syed DN, Ahmad N, et al. Fisetin: a dietary antioxidant for health promotion. Antioxid Redox Signal. 2013 Jul 10;19(2): 151-62.
  35. Cho Y, Chung JH, Do HJ, et al. Effects of fisetin supplementation on hepatic lipogenesis and glucose metabolism in Sprague-Dawley rats fed on a high fat diet. Food Chem. 2013 Aug 15;139(1-4):720-7.
  36. Gaballah HH, El-Horany HE, Helal DS. Mitigative effects of the bioactive flavonol fisetin on high-fat/high-sucrose induced nonalcoholic fatty liver disease in rats. J Cell Biochem. 2019 Aug;120(8):12762-74.
  37. Jeon TI, Park JW, Ahn J, et al. Fisetin protects against hepatosteatosis in mice by inhibiting miR-378. Mol Nutr Food Res. 2013 Nov;57(11):1931-7.
  38. Liou CJ, Wei CH, Chen YL, et al. Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid beta-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice. Cell Physiol Biochem. 2018;49(5):1870-84.
  39. Kan E, Kilickan E, Ayar A, et al. Effects of two antioxidants; alpha-lipoic acid and fisetin against diabetic cataract in mice. Int Ophthalmol. 2015 Feb;35(1):115-20.
  40. Available at: Accessed June 22, 2020,
  41. Available at: Accessed September 1, 2020.
  42. Kashyap D, Sharma A, Sak K, et al. Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy. Life Sci. 2018 Feb 1;194:75-87.
  43. Kashyap D, Garg VK, Tuli HS, et al. Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential. 2019 May 6;9(5):174.
  44. Wang L, Tu YC, Lian TW, et al. Distinctive antioxidant and antiinflammatory effects of flavonols. J Agric Food Chem. 2006 Dec 27;54(26):9798-804.
  45. Park HH, Lee S, Son HY, et al. Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells. Arch Pharm Res. 2008 Oct;31(10):1303-11.
  46. Farsad-Naeimi A, Alizadeh M, Esfahani A, et al. Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients. Food Funct. 2018 Apr 25;9(4):2025-31.
  47. Ravichandran N, Suresh G, Ramesh B, et al. Fisetin modulates mitochondrial enzymes and apoptotic signals in benzo(a)pyrene-induced lung cancer. Molecular and Cellular Biochemistry. 2014 2014/05/01;390(1):225-34.
  48. Kang KA, Piao MJ, Madduma Hewage SRK, et al. Fisetin induces apoptosis and endoplasmic reticulum stress in human non-small cell lung cancer through inhibition of the MAPK signaling pathway. Tumor Biology. 2016 2016/07/01;37(7):9615-24.
  49. Suh Y, Afaq F, Johnson JJ, et al. A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kB-signaling pathways. 2008;30(2): 300-7.
  50. Lim JY, Lee JY, Byun BJ, et al. Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells. Toxicology Reports. 2015 2015/01/01/;2:984-9.
  51. Jia S, Xu X, Zhou S, et al. Fisetin induces autophagy in pancreatic cancer cells via endoplasmic reticulum stress- and mitochondrial stress-dependent pathways. Cell death & disease. 2019;10(2):142.
  52. Bhat TA, Nambiar D, Pal A, et al. Fisetin inhibits various attributes of angiogenesis in vitro and in vivo—implications for angioprevention. 2011;33(2):385-93.
  53. Bhat TA, Nambiar D, Pal A, et al. Fisetin inhibits various attributes of angiogenesis in vitro and in vivo--implications for angioprevention. 2012 Feb;33(2):385-93.
  54. Li J, Gong X, Jiang R, et al. Fisetin Inhibited Growth and Metastasis of Triple-Negative Breast Cancer by Reversing Epithelial-to-Mesenchymal Transition via PTEN/Akt/GSK3beta Signal Pathway. Front Pharmacol. 2018;9:772.
  55. Karin O, Agrawal A, Porat Z, et al. Senescent cell turnover slows with age providing an explanation for the Gompertz law. Nat Commun. 2019 Dec 2;10(1):5495.
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