Removal of Senescent Cells “Might Transform Medicine”

On July 9, 2018, the world awoke to news from the Mayo Clinic that many age-related afflictions can be reversed by eliminating senescent cells from old mice.¹

In addition to regaining aspects of youthful health, the old mice whose senescent cells were selectively removed lived 36% longer.¹

This is not the first study showing these effects. What makes it exceptional is the meticulous way it was conducted.

The first part of the study involved transplanting a few senescent cells into young mice. This caused the young mice to endure physical decline characteristic of degenerative aging. When senescent cells were transplanted into old mice, the same toxic effects occurred and the mice died sooner.

But with oral administration of compounds that remove senescent cells, physical dysfunction was alleviated and lifespan markedly increased.

The incredible news is that novel ways are being developed to help remove senescent cells from aging humans today!

Why Senescent Cells Accumulate

As cells age, most undergo a beneficial elimination process known as apoptosis.

If all aged cells properly self-eliminated, we would see improvements in healthy lifespans.²

Instead, too many senescent cells linger. These aged cells emit signals that promote inflammation, injure healthy cells, and block regenerative factors that may improve one’s health.³

This scenario occurs inside our bodies, whereby senescent cells fail to undergo apoptosis (normal cell elimination). These pesky senescent cells emit inflammatory-type signals that spread to healthy cells and cause them to deteriorate.

An Old Problem with New Solutions

I was informed about senescent cells in the late 1990s by a brilliant researcher. He made it clear that if we were to achieve meaningful control over aging, we had to selectively remove senescent cells that accumulate and create metabolic havoc.

The problem back then was there was no valid approach to accomplish this.

Starting around year 2014, scientists at the Mayo Clinic and Scripps Research Institute began investigating senolytics, which are compounds that induce normal elimination of senescent cells.⁴

Remarkable Results

The box on the previous page is from a presentation I give to advocate for accelerated age-reversal research. This slide highlights findings from a groundbreaking (year 2015) animal study that found remarkable rejuvenation effects in response to aggressive senolytic therapy.

This 2015 study⁴ was followed by another study funded in part by the National Institutes of Health (NIH) published in 2017.⁵

The 2017 study looked at age-accelerated mice treated with a senolytic compound. The findings showed improvements in grip strength, coat condition, movement, and overall health. This study also revealed improvement in a biomarker of senescent cells in the kidney compared with control mice.⁵

Favorable Media Coverage

These studies generated worldwide headlines, with scientists describing the potential of senolytic compounds to reverse aging in humans.

In a review published by The American Geriatrics Society (2017), senolytics were described as having potential to:

“…transform geriatric medicine by enabling prevention or treatment of multiple diseases and functional deficits in parallel, instead of one at a time.”²

The authors of this review explained how reducing the “senescent cell burden” can lead to less inflammation with enhanced function of stem cells.²

The review went on to describe how senescent cells destroy the knee joints of healthy mice.⁶ These findings have encouraged people with osteoarthritis to self-experiment with senolytic compounds, with encouraging results being reported.

Of interest is that senolytics do not have to be used continuously to derive benefits. This corroborates current strategies whereby people are using senolytics intermittently (“on” and “off” periods).

This 2017 review concluded that after clinical trials are completed:

“…it is conceivable that the rapidly emerging repertoire of senolytic agents might transform medicine as we know it.”²

Researchers have further remarked that the introduction of senolytics into clinical practice could be transformative when stating:

“Our goal is to achieve the same success in humans as we have in preclinical animal models in efforts to prevent or delay the conditions associated with aging.”⁷

Human senolytic studies are being pursued by a number of physician/scientists. We look forward to reporting on them after more long term data is gathered.

Practical Senolytic Approaches

Early stage research on senolytics indicates that intermittent dosing may be an ideal approach. In other words, the strategy is to selectively induce senescent cell apoptosis for a limited time, and then cease until more senescent cells accumulate.

Drugs that purge senescent cells are being clinically studied. Some individuals are self-experimenting today with senolytic drugs + high-dose quercetin.

In a cell culture study, the drug dasatinib eliminated human senescent fat cell progenitors.⁴ Quercetin was more effective against senescent human endothelial cells and bone marrow stem cells.⁴

Improving circulation via enhanced endothelial function and enabling more potential stem cell release from bone marrow is important. Removing fat-cell progenitors is desirable, since these cells can negatively impact surrounding tissue and are linked to metabolic dysfunction.⁸

Until recently, people seeking to achieve senolytic benefits were challenged to take large-doses of quercetin, and many don’t yet want to try dasatinib. A new quercetin phytosome eliminates the need to ingest large amounts of quercetin.

Another discovery suggests that a tea extract containing theaflavins provides some of the same senolytic properties targeted by dasatinib,^9-11 and other senolytic drugs.¹²

How to Purge Senescent Cells Today

A new quercetin phytosome provides approximately 50 times greater oral bioavailability compared to typical quercetin supplements.¹³

This enables 74 mg of this quercetin phytosome (providing 25 mg quercetin) to deliver a dose approximately equivalent to about 1,250 mg of typical quercetin. This empowers more people to achieve greater amounts of intact and unmodified quercetin into their bloodstream.

In addition to having a similar mechanism of action as dasatinib,^9-11 preclinical evidence indicates the senolytic potential of black tea theaflavins.¹⁴ Based on our interpretation of the current research findings, we suggest most people over age 35 consider taking a once weekly dose of:

• 74 mg of quercetin phytosome

• 275 mg of theaflavins

Those taking lower doses of regular quercetin for its other benefits may continue to do so and use the new phytosome delivery formula on an intermittent schedule. The article on page 6 of this issue describes this low-cost and novel approach to removing senescent cells by taking theaflavins and quercetin phytosome just one time each week.

The cost of this once-weekly senolytic nutrient approach is less than $7 a month.

Restore Youthful Circadian Sleep Patterns

Aging and erratic lifestyle disrupts our ability to retain circadian balance via restorative sleep.

Healthy circadian rhythm function is reliant on expression of genes that “turn on” vital signaling pathways throughout the body. It’s why we often feel “systemically” terrible when we suffer a night of broken sleep or insomnia.

A citrus-peel extract containing nobiletin has been shown to restore circadian gene expression in mice. An article on page 38 of this issue describes how people with disrupted circadian rhythms may derive benefit.

Annual Super Sale Savings!

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This is our 30^th annual Super Sale. It begins November 12, 2018, and extends to January 31, 2019.

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To order the health-preserving nutrients you need today, call 1-800-544-4440 (24 hours).

For longer life,

William Faloon, Co-Founder
Life Extension Buyers Club

References

1. Xu M, Pirtskhalava T, Farr JN, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24(8):1246-56.
2. Kirkland JL, Tchkonia T, Zhu Y, et al. The Clinical Potential of Senolytic Drugs. J Am Geriatr Soc. 2017;65(10):2297-301.
3. 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;17(4):324-8.
4. Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14(4):644-58.
5. Fuhrmann-Stroissnigg H, Ling YY, Zhao J, et al. Identification of HSP90 inhibitors as a novel class of senolytics. Nat Commun. 2017;8(1):422.
6. Xu M, Bradley EW, Weivoda MM, et al. Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice. J Gerontol A Biol Sci Med Sci. 2017;72(6):780-5.
7. Available at: https://www.sciencedaily.com/releases/2017/09/170904093428.htm. Accessed August 6, 2018.
8. Tchkonia T, Morbeck DE, Von Zglinicki T, et al. Fat tissue, aging, and cellular senescence. Aging Cell. 2010;9(5):667-84.
9. Noberini R, Koolpe M, Lamberto I, et al. Inhibition of Eph receptor-ephrin ligand interaction by tea polyphenols. Pharmacol Res. 2012;66(4):363-73.
10. Noberini R, Lamberto I, Pasquale EB. Targeting Eph receptors with peptides and small molecules: progress and challenges. Semin Cell Dev Biol. 2012;23(1):51-7.
11. Ting PY, Damoiseaux R, Titz B, et al. Identification of small molecules that disrupt signaling between ABL and its positive regulator RIN1. PLoS One. 2015;10(3):e0121833.
12. Leone M, Zhai D, Sareth S, et al. Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic Bcl-2-family proteins. Cancer Res. 2003 Dec 1;63(23):8118-21.
13. Supplier Internal Study. A randomized and crossover pharmacokinetic study of Quercetin 500mg., Quercetin Phytosome 500 mg. and Quercetin Phytosome 250 mg. administered in a single dose to healthy volunteers under fasting conditions. Data on File. 2017.
14. Han X, Zhang J, Xue X, et al. Theaflavin ameliorates ionizing radiation-induced hematopoietic injury via the NRF2 pathway. Free Radic Biol Med. 2017;113:59-70.