Senescent Cells Are Weakening Your Bones, Here’s What To Do About It
Newly published research has revealed one more tool for reversing osteoporosis. And the good news is that you can easily incorporate this new approach to improving bone quality and density into your current bone-healthy habits.
It has to do with controlling the accumulation of senescent cells, which are cells that have stopped dividing due to damage or aging. In today’s article, you’ll learn about the negative impact of senescent cells on your bones and two natural compounds that science has confirmed can effectively eliminate them, helping to prevent and reverse bone loss.
Senescence, Cells, And Bone
Senescence is a cellular mechanism activated in stressed or damaged cells to end cellular growth and reproduction. When cells enter senescence, they release chemical compounds that signal the immune system to destroy them. 1
However, as we get older, our bodies become less adept at removing senescent cells, resulting in the accumulation of the chemical compounds they release. These compounds cause inflammation, tissue dysfunction and deterioration.2
Therefore , senescent cells play a direct role in aging and age-related conditions that are caused or exacerbated by low-grade chronic inflammation including atherosclerosis, cancer, Alzheimer’s disease, type 2 diabetes, and osteoarthritis.3
Until recently the role of senescent cells in osteoporosis was unclear. But research conducted at the Mayo Clinic has concluded that the chemical compounds released by accumulating senescent cells are a driving factor of bone loss.4
When cells enter senescence, they release inflammatory compounds to mark themselves for removal from the body. When aging slows the removal process, the accumulation of inflammatory compounds contributes to age-related conditions, including osteoporosis.
The Eradication Of Senescent Cells And Osteoporosis
The Mayo Clinic study used multiple methods to target senescent cells in naturally aged mice with demonstrated bone loss. The mice’s age was the equivalent of older than 70 human-years. The study targeted senescent cells in three ways:
- A genetic intervention that eradicated senescent cells
- An enzyme-inhibiting drug that prevented the senescent cells from releasing their proinflammatory compounds
- A senolytic drug that eliminated senescent cells
All three methods resulted in enhanced bone mass and strength. The treatments didn’t have the same effect on younger mice, indicating that the senescent cells are linked explicitly to age-related bone loss. The beneficial effects of the experimental treatments were due to lower bone resorption paired with either maintained or increased bone formation.
Here is the conclusion of the study:
“Collectively, these data establish a causal role for senescent cells in bone loss with aging, and demonstrate that targeting these cells has both anti-resorptive and anabolic effects on bone. Given that eliminating senescent cells and/or inhibiting their proinflammatory secretome also improves cardiovascular function, enhances insulin sensitivity, and reduces frailty, targeting this fundamental mechanism to prevent age-related bone loss suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.”4
If the “novel treatment strategy” involves the senolytic drugs used in the study, then this strategy will prove unsafe and undesirable. The mice were given a combination of dasatinib (Sprycel), which is a drug used to treat certain forms of leukemia, with quercetin, a plant polyphenol.
The authors emphasized that this drug only needs to be administered intermittently to achieve the desired effect, which they claim would reduce the risk of side effects when compared to daily use. Once a day is the typical dosing schedule for dasatinib.
Sprycel (dasatinib), taken once daily for chronic myeloid leukemia has an array of severe side effects including:5
- Anemia (low blood cell count)
- Severe bleeding that can lead to death
- Fluid retention in the lining of your lungs, stomach cavity, and the sac around your heart
- Abnormal heart rate and other heart problems
- Heart attack that can lead to death
- Pulmonary Arterial Hypertension (PAH)
- Severe skin reactions including sore mouth, sore throat, blistering and peeling
- Shortness of breath
- Muscle pain
Even if the risk of these side effects is lower on a different dosing scheduling, they aren’t risks worth taking, especially when there are safer alternatives. We know that senescent cells contribute to bone loss, but you don’t need to take life-threatening cancer drugs to target them.
The study found that targeting senescent cells improved bone mass and strength. Mice were given Sprycel (dasatinib), a drug used to treat myeloid leukemia known to have many dangerous side effects, combined with the polyphenol quercetin.
Fisetin: An Effective And Safe Senolytic Antioxidant
Savers may already be familiar with the polyphenol antioxidant fisetin.
Fisetin fights inflammation via multiple metabolic pathways.6 That already makes fisetin a powerful all-natural tool for reducing fracture risk. Here are some of fisetin’s beneficial functions:
- Inhibits the formation of collagen-destroying Advanced Glycation End products (AGEs)7
- Maintains levels of the Master Antioxidant glutathione6
- Increases resveratrol levels by slowing its breakdown8
- Protects brain function and prevents cognitive decline9
- Protects mitochondria6
- Prevents DNA damage, guarding against cancer10
We can now add to the list that fisetin eliminates senescent cells, reversing a variety of age-related conditions, including osteoporosis. A study released in October of this year found that fisetin is a potent senolytic. This passage from the study describes the results:
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.2
This finding confirms fisetin as an essential component to naturally reverse osteoporosis. And fortunately for Savers, fisetin is present in many fruits and vegetables that are likely already a part of your pH-balanced diet.
Sources of fisetin include:
* Foundation Foods
Make sure you include these foods in your diet to get the bone-building senolytic effects of fisetin.
The polyphenol antioxidant fisetin has been found to be a potent senolytic, making it a safe and natural way to eliminate senescent cells thereby improving bone quality and density.
Tocotrienols: Potent And Natural Senolytic Compounds
Tocotrienols are a group of chemicals that belong to the Vitamin E (tocopherol) family. Vitamin E has been shown to help build strong muscles and protect cells against damage from free-radicals. This, in turn, helps to build strong bones.
Like fisetin, tocotrienols are antioxidants. Some of their overall health benefits include11:
- Neuroprotective properties
- Anticancer properties
- Lowering cholesterol
- Fighting inflammation
Tocotrienols have also been found to prevent cellular aging by modulating cell proliferation signaling pathways. A study published in 2015 found that tocotrienols slow the cellular changes associated with aging, and promote cell division and specialization.12 Slower aging prevents cells from reaching the phase of senescence, in which cells release the chemical compounds that cause inflammation.12
Tocotrienols are naturally occurring compounds that may already be a part of your diet. Top sources of tocotrienols include:
The bioavailability of tocotrienols is limited, but studies have found that they become detectable in appreciable levels in the plasma after supplementation.11 Therefore, to make the most of the senolytic function of tocotrienols, it is best to take a supplement in addition to consuming the foods mentioned above. At the Save Institute, we recommend taking a daily dose of 500 to 800 mg of a tocotrienol complex supplement consisting of alpha, beta, gamma, and delta tocotrienols.
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Tocotrienols, compounds that are part of the Vitamin E family, offer a variety of overall and bone health benefits, including senolytic properties. You can most effectively absorb these natural antioxidants in a supplement form, with a recommended daily dosage of 500 to 800 mg.
Keep Your Cells Young To Keep Your Bones Strong
Through a deeper understanding of nutrition and biology, we can address a variety of health problems at their root, including cellular senescence, and take a multi-pronged approach to naturally build bone density and strength.
1 Jan M. van Deursen. “The role of senescent cells in ageing.” Nature. 2014 May 22; 509(7501): 439–446. Web. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214092/
2 Yousefzadeh, Matthew J. et al. “Fisetin is a senotherapeutic that extends health and lifespan.” EBioMedicine, Volume 36 , 18 – 28. Web. https://www.ebiomedicine.com/article/S2352-3964(18)30373-6/fulltext
3 Zhu Y1, Armstrong JL, Tchkonia T, Kirkland JL. “Cellular senescence and the senescent secretory phenotype in age-related chronic diseases.” Curr Opin Clin Nutr Metab Care. 2014 Jul;17(4):324-8. Web. https://www.ncbi.nlm.nih.gov/pubmed/24848532
4 Joshua N Farr, et al. “Targeting cellular senescence prevents age-related bone loss in mice.” Nature Medicine, 2017. Web. https://www.nature.com/articles/nm.4385
6 Sengupta B, Banerjee A, Sengupta PK. “Interactions of the plant flavonoid fisetin with macromolecular targets: insights from fluorescence spectroscopic studies.” J Photochem Photobiol B. August 2005. 80(2):79-86. Web. http://www.ncbi.nlm.nih.gov/pubmed/16038806
7 Maher, P. “Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin.” Genes Nutr. 2009 Sep 10.
8 De Santi, C., et al. “Sulphation of resveratrol, a natural compound present in wine, and its inhibition by natural flavonoids.” Xenobiotica. 2000 Sep;30(9):857-66.
9 Currais, A., et al. “Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer’s disease transgenic mice.” Aging Cell. April 2014. 13(2):379-90. Doi: 10.1111/acel.12185. Web. http://www.ncbi.nlm.nih.gov/pubmed/24341874
10 Watjen, W., et al. “Low concentrations of flavonoids are protective in rat H4IIE cells whereas high concentrations cause DNA damage and apoptosis.” J Nutr. 2005 Mar;135(3):525-31.
11 Haseeb Ahsan, et al. “A review of characterization of tocotrienols from plant oils and foods.” J Chem Biol. 2015 Apr; 8(2): 45–59. Web. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392014/
12 Khor SC, et al. “Tocotrienol-rich fraction prevents cellular aging by modulating cell proliferation signaling pathways.” Clin Ter. 2015;166(2):e81-90. Web. https://www.ncbi.nlm.nih.gov/pubmed/25945449