Senolytics, Cellular Senescence, and the Fight to Reverse Aging: Part 1

What is cellular senescence and why is it so important to reverse it?

All adults have about 50 trillion individual living cells at any time. As cells age, they die and are replaced by new copies. An example is when we scrape a knee. The skin is damaged, leaving raw, sometimes bloody tissue exposed to germs and other dangers which could damage the whole body by poison or infection if left exposed. The damaged skin cells flake off, a scab forms to protect the underlying area, then drops off, leaving the new skin healed as good as before. This process happens on the inside as well-and that’s a problem.

Even without damage about 3 million of our cells die… EACH SECOND!

That’s 259,200,000,000 every 24 hours. Most are removed by normal processes – breathing, urine, solid removal, and sweating. Some though stay within the body for longer until removed as part of the metabolic/digestive cycles.
This still leaves a lot of dead cells hanging around. Over time they bunch together and stick to the linings of the gut, brain, blood vessels and other organs. From the age of around 20 when our body systems begin to break down (which is the beginning of the degenerative disease called aging) our bodies become less efficient at removing dead cells. Some diseases accelerate this process. One is COVID-19. Getting COVID-19 makes you biologically age faster – one reason to attack the enemy by getting the best protection available.

One result is like the furring of a kettle or a car radiator, both caused by mineral deposits. Other furring is formed by minerals, dead cells, and unsaturated fats, which contribute to Alzheimer’s – the classic disease of the later years, which is accelerated when there are too many free radicals in the body. Senolytics help to correct that imbalance. Additionally, we rust up. We have water and iron in our blood, which combined with oxygen, results in iron oxide.

That sticks to the dead cell masses, increasing them until one is big enough to block something. If that something is a major vein or artery, that’s a stroke, heart attack, or pulmonary embolism. If the workings of a machine get clogged, the machine stops. The older we get, the greater that risk – not only of death, but the restriction of the blood system and organ function, two of the factors which make older people physically and mentally frail.

So, what can we do to stop- or even reverse this horror – to clean out our systems to the condition they were at age 20? The answer is that at this point, we can’t, because we can’t get them all out, leaving the pitting and scarring they caused which compromises free-flow. But we can do a lot to largely reverse it and for younger people to prevent it. To do so, an agent is needed which finds and flushes out senescent cells before and after they build up.

These exist. They are called senolytics, from the Latin senilis – old, aged, to be senile.

There are currently two popular options, pharmaceutical and natural ones. The well-tested and proven pharmaceutical ones are 2 synthetic penicillin-based drugs, Rapamycin and Azithromycin. Both have a positive senolytic effect, both also have some significant risks and often unpleasant side effects. The second half of this article examines the gentler and equally effective natural alternatives, quercetin and fisetin.

One excellent source of quercetin is from Double Wood Supplements:

Double Woods Quercetin

References and Works Cited

Kumiko Ishige, David Schubert, Yutaka Sagara, Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms, Free Radical Biology and Medicine, Volume 30, Issue 4, 2001, Pages 433-446, ISSN 0891-5849.

Sagara, Y., Vanhnasy, J. and Maher, P. (2004), Induction of PC12 cell differentiation by flavonoids is dependent upon extracellular signal‐regulated kinase activation. Journal of Neurochemistry, 90: 1144-1155.

Wen-bin He, Kazuho Abe, Tatsuhiro Akaishi, Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo, Journal of Pharmacological Sciences, Volume 136, Issue 1,2018, Pages 42-45, ISSN 1347-8613

Bliss, T.V, Collingridge. A synaptic model of memory: long-term potentiation in the hippocampus. Nature, 361 (1993), pp. 31-39.

Maher, T. Akaishi, K. Abe. Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory, Proc Natl Acad Sci USA, 103 (2006), pp. 16568-16573.

Priprem A, Watanatorn J, Sutthiparinyanont S, Phachonpai W, Muchimapura S. Anxiety and cognitive effects of quercetin liposomes in rats. Nanomedicine. 2008 Mar;4(1):70-8. doi: 10.1016/j.nano.2007.12.001. Epub 2008 Jan 30. PMID: 18249157.

Jeong, Jae-Hoon et al. Effects of low dose quercetin: cancer cell-specific inhibition of cell cycle progression. Journal of cellular biochemistry vol. 106,1 (2009): 73-82. doi:10.1002/jcb.21977

Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet. 1993 Oct 23;342(8878):1007-11. doi: 10.1016/0140-6736(93)92876-u. PMID: 8105262.

Wang DM, Li SQ, Wu WL, Zhu XY, Wang Y, Yuan HY. Effects of long-term treatment with quercetin on cognition and mitochondrial function in a mouse model of Alzheimer’s disease. Neurochemistry Research. 2014 Aug;39(8):1533-43. doi: 10.1007/s11064-014-1343-x. Epub 2014 Jun 4. PMID: 24893798.

By |2021-02-23T21:02:50+00:00February 23rd, 2021|

About the Author:

Dr. Ian Hale earned his BA (Honors) in Cultural Studies (English and History) at the University of Portsmouth, before receiving his Teaching License from Bristol University (England). He earned his M.A. in Professional Special Education Studies, which included genetics, neurology and haemotology at Bath Spa University in 2008. He received his Ph.D. (H.C.) in Humanitas at UNESCO in 2006. Prof Hale has guest lectured at Touro Law School, Jewish Law Institute under Prof Samuel L Levine, New York on Neurodiversity. He is the author of and Prof Hale also holds an International Diploma in Integrated Medicine.