Senescent Cells & Holistic Medicine

Senescent cell are cells  that some scientists call zombie cells because they refuse to die. Dysfunctional, they have ceased to divide and just linger in tissues in a state of inflammatory “decomposition”.

Metabolically active, these cells are normally useful and get eliminated by the immune system or destroyed in the form of programmed cell death. If they don’t, if they accumulate in the body, they accelerate the aging process by harming surrounding cells over time. Senescent cells are removed from the body by a robust immune system.  The immune cells that participate in the clearance of senescent cells are natural killer cells, macrophages, and T cells.

Senescent cells can represent up to 10% – 15% of cells in the body and up to 20% in the skin.  1  2    Senescent cells can also be found all over the body and in may accumulate in certain body organs.  The most common areas of the body and organs that senescent cell accumulate are the following: Skin – Senescent cells can often accumulate in the fibroblasts, which are cells in the skin that are essential for producing new skin tissue.  3 Joints – Old cartilage-producing cells (chondrocytes) in the joints can accumulate which can lead to osteoarthritis.  4  5 Brain – As the brain ages, it starts to accumulate senescent cells which secrete inflammatory cytokines.  This may then lead to the age related brain disorders like Alzheimer’s and Parkinson’s disease.  6  Heart – Senescent cells accumulate in the heart tissue which may lead to cardiovascular disease.  The endothelium layers of the blood vessels can also accumulate senescent cells. Lungs – Senescent cells have been discovered in the lungs of smokers.  7 Liver – Senescent cells can accumulate in the liver and compromise its function and lead to conditions like non-alcoholic fatty liver disease (NAFLD).  8  9 Lymph Nodes – The lymph nodes of aged individuals may accumulate senescent T cells.  10

The Deep Cause: an un-holistic life with its accompanied immune deficiency

The problem with senescent cells is their accumulation in various body organs and tissue and not the fact they are produced by the body. Senescence scientists believe that senescent cells are similar to cancer cells in that they express pro-survival networks that help them resist apoptosis, (programmed cell death).

The evidence shows that these senescent calls increase with age and an unholistic lifestyle that compromises the immune system, because of which these senescent cell won’t be cleared from the body efficiently.  11 With an unholistic lifestyle, telomeres tend to shorten and this triggers a DNA damage response with elevated reactive oxygen species (ROS) causing further DNA damage that which causes the activation of oncogenes and cell-cell fusion, inter alia.  

Since senescent cells are produced at a higher frequency with age and stress, these aging cells and tissues demonstrate a steady accumulation of cells that show DNA damage12  13

Once the senescent cells accumulate in the body, they secrete pro-inflammatory cytokines, chemokines, and protein digesting extracellular matrix proteases, which together constitute the senescence-associated secretory phenotype or SASP.  14  15  16

The Solution to Senescent Cells 

To date, scientists have not found a way to stop the process and development of senescent cells in the body.  So instead of focusing on research on how to stop senescent cells from developing, the focus has been on identification of approaches to remove damaged, senescent cells.  By removing inflammation prone senescent cells from the body, it could lead to a state of longer healthspans and lifespans and a decrease of the diseases linked to these senescent cells.

Senolytics

Research scientists have invented the term “Senolytics” as drugs that selectively induce death of senescent cells.  In an article published in August 2015 in Aging Cell entitled The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs, the authors stated that:

“The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age-related chronic diseases. Here, we describe the rationale for identification and validation of a new class of drugs termed senolytics, which selectively kill senescent cells. (…) These results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.”  17

The authors of the Aging Cell article were able to find two compounds among the 46 they tested that would effectively induce the death of senescent cells.  These two compounds are: Dasatinib, a cancer drug marketed under the name Sprycel, and Quercetin, a natural compound. Tests in cell cultures showed that these two compounds did selectively induce death of senescent cells, targeting different cells. The dasatinib eliminated senescent human fat cell progenitors. On the other hand, Quercetin was found to be most effective in eliminating senescent cells in Human endothelial cells  and mouse bone marrow stem cells (Ibid).

Quercetin

Quercetin caused a 50% reduction of senescent cells in the Aging Cell study.  The authors stated that:

“Note that at 10 μm Q, nonsenescent HUVECs achieved a 2-3-fold increase in cell number between days 0 and 3, while parallel cultures of senescent cells were reduced by 50%, indicating selective killing of senescent cells.  18

The authors concluded their study by stating the following:

“The identification of approaches to remove damaged, senescent cells would have a tremendous impact on quality of life and burden of age-related chronic diseases. To identify agents able to kill senescent cells, we hypothesized that senescent cells, like cancer cells, are dependent on anti-apoptotic pathways to ensure their survival following stress and damage. Based on this hypothesis, here we demonstrate that senescent cells indeed are susceptible to selective clearance by targeting pro-survival mechanisms using siRNAs and drugs, even at doses insufficient to kill normal proliferating or differentiated, quiescent cells. This observation opens up new approaches to develop clinically relevant small molecules or biologics that selectively eliminate senescent cells from nongenetically modified individuals, acting as senolytic agents. The prototype senolytic agents identified here, dasatinib and quercetin, have the ability to alleviate multiple aging phenotypes, as would be predicted if they truly act by eliminating senescent cells.”  19

Quercetin is found in a variety of foods, (see list above), including in raw capers, canned capers, lovage, sorrel and radish leaves.  The Phenol-Explorer database lists the content of quercetin in various foods. Quercetin is also available as a supplement.  Quercetin dihydrate – The most common form of quercetin, yet it is insoluble in water and has poor bioavailability Quercetin 3-O-beta-glucoside (Isoquercetin) – Isoquercitrin and isoquercetin are naturally occurring forms of quercetin with a glucoside side chain that enhances bioavailability. Alpha-Glycosyl Isoquercitrin – provides the benefits of the flavonoid quercetin with better absorption and superior bioavailability.  Alpha-Glycosyl Isoquercitrin has 3 times the bioavailability of isoquercetin and nearly 18 times the bioavailability of quercetin aglycone. Quercetin Phytosome (Sophora japonica concentrate) – sunflower sourced phosphatidylcholine for optimal absorption.

Quercetin in combination with Reveratrol

Resveratrol has become a popular “anti-aging” supplement because of its beneficial effect on gene expression.

Quercetin has been shown to make more resveratrol available to the body. It does this by reducing the rate of resveratrol degradation (sulfation) in the liver and enhancing its bioavailability.

When resveratrol is ingested, about 70%of it is absorbed from the intestine into the blood.73 The absorbed resveratrol is then transported to the liver. When the liver adds sulfate groups, there is some deactivation of the resveratrol.74

Since quercetin has favorable influences on the bioavailability of resveratrol, it makes sense to take these two nutrients together.75 Interestingly, while red wine is known to contain small amounts of resveratrol, it usually contains even more quercetin, meaning the health benefits associated with red wine may be due to both its resveratrol and quercetin content (along with other polyphenols).75.76

 Resources:

Quercetin dihydrate

Quercetin 3-O-beta-glucoside (Isoquercetin)

Alpha-Glycosyl Isoquercitrin

Quercetin Phytosome

 

Professor Joubert teaches how to extend a healthy cancer-free Lifespan to 122 years thanks to safe, efficient and cost friendly breakthrough protocols. Working on a documentary and book that redefines Medicine in light of new discoveries, ancient wisdoms, innovative research and holistic science, he can be nonetheless available to coach patients back to homeostasis, wellbeing & Joie de Vivre. On occasion, Pr. Joubert can also coach health professionals to better protect their holistic practice when they must deviate from outdated and-or irrational mainstream “standards of care” in order to genuinely serve their patients, evidence-strong Science and internationally recognized human rights. For details, see the links called “Contact” and “Mission” (under the “About” link).

Posted in Longevity Pathways

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