The Science of Senescent Burden
Every day, the body eliminates cells that are abnormal or damaged through apoptosis, which prevents the build-up of dysfunctional cells within tissues. As a normal, daily function, this process unfortunately changes as we age. Older cells stop working properly, which includes losing the ability to complete normal tasks and the ability to divide. Instead of dying, however, some of these cells continue to stay put and can accumulate in the tissues in what is known as cellular senescence. These senescent cells can create a burden within the body, and contribute to many of the conditions seen with aging, such as arthritis, reduced vision, cardiovascular diseases, dementia, and cancer. 1-5
As senescent cells do not function properly, they can keep surrounding cells from operating at their peak, in addition to spreading dysfunction systemically through the secretion of compounds known as senescence-associated secretory phenotype. 6,7 It is these compounds that keep the dysfunction going, as well as activates chronic inflammation in the body—a known culprit in premature aging and diseases of aging. 6,7
Plant-derived approaches to address senescent burden Senolytics are therapies that selectively destroy senescent cells so as to produce renewal in tissues, and may include chemical-based or plant-based compounds. Theaflavins and quercetin feature plant-based senolytic properties and are found in everyday food and drink. Quercetin is a plant pigment in fruits and vegetables such as onions, berries, and apples; theaflavins are found in black tea. In particular, theaflavins has been shown to mimic a similar mechanism of action as pharmaceutical senolytics like dasatinib and navitoclax, which are used in the treatment of certain cancers and leukemia. With theaflavins, the Bcl-2 family of proteins is inhibited, which helps to force senescent cells into cell death, as well as helps to decrease the activity of tyrosine kinase receptors, which is how pharma drug dasatinib helps stop the spread of malignant cells. 8 Additionally, theaflavins help modulate cellular pathways that are indicated with cellular senescence. 9 In a human study by researchers at the Mayo Clinic of quercetin and dasatinib senolytic therapy in patients with lung disease, patients were placed on a senolytic regimen of 1,250 mg/day of quercetin and 100 mg/day of dasatinib for three days a week, for three weeks. Noticeable improvements were seen within the short time span of patients’ physical functioning. 10
Using a combination of theaflavins and quercetin may offer senolytic action available without a prescription, as well as the potential for turning back the hands of time.
References
1. Baker DJ, Wijshake T, Tchkonia T, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011 Nov 2;479(7372):232-6.
2. Kirkland JL. Inflammation and cellular senescence: potential contribution to chronic diseases and disabilities with aging. Public Policy and Aging Report. 2013;23:12-5.
3. Kirkland JL, Tchkonia T. Clinical strategies and animal models for developing senolytic agents. Exp Gerontol. 2015 Aug;68:19-25.
4. Tchkonia T, Zhu Y, van Deursen J, et al. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest. 2013 Mar;123(3):966-72.
5. 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.
6. Borodkina AV, Deryabin PI, Giukova AA, et al. “Social Life” of Senescent Cells: What Is SASP and Why Study It? Acta Naturae. 2018 Jan-Mar;10(1):4-14.
7. Coppe JP, Desprez PY, Krtolica A, et al. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010;5:99-118.
8. Mizuno H, Cho YY, Zhu F, et al. Theaflavin-3, 3’-digallate induces epidermal growth factor receptor downregulation. Mol Carcinog. 2006 Mar;45(3):204-12.
9. Han X, Zhang J, Xue X, et al. Theaflavin ameliorates ionizing radiation-induced hematopoietic injury via the NRF2 pathway. Free Radic Biol Med. 2017 Dec;113:59-70.
10. Hickson LJ, Langhi Prata LGP, Bobart SA, et al. Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease [published correction appears in EBioMedicine. 2020 Feb;52:102595]. EBioMedicine. 2019;47:446‐456.
