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How the world got lost on
the road to an anti-aging pill
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January 1, 2017: by Bill Sardi
Ignoring prior science that shows the red wine molecule resveratrol blocks oxidative stress and convincingly prevents cell senescence, a researcher at Erasmus University Medical Center in the Netherlands says elimination of senescent cells from an aging body is now plausible.
As cells age they lose their ability to divide and replicate. This so-called cellular senescence is an obvious hindrance to the growth of cancerous cells but removal of senescent cells from animals resulted in animals hair regrowth, improved organ function and faster-paced running. [Science Daily Dec 29, 2016] So reversal of cell senescence (not just slowing senescence) appears to be a bona fide anti-aging strategy.
Peter de Keizer, writing in Trends in Molecular Medicine, in his recent essay entitled “The Fountain of Youth By Targeting Senescent Cells?” says to reverse aging one “needs not only to remove rust and broken parts, but also remove these.”
De Keizer is talking about stem cells being summoned to differentiate into youthful heart, muscle, brain cells. [Trends Molecular Medicine Jan 2017] But just how to remove senescent cells and leave healthy cells unaffected?
De Keizer points to targeting cell-signaling pathways called FOXO, to combat senescence and stimulate tissue rejuvenation. FOXO regulates p21 enzyme inhibitor, a prominent factor in cellular senescence growth arrest, and inhibit B-catenin, a regulator of cell stemness. Stem cells are cells that have not yet been defined by form or function yet. They are necessary for cell and tissue renewal and certainly for reversal of aging. A proposed therapy that alters FOXO gene activity would stimulate cellular rejuvenation and inhibit cell senescence writes de Keizer.
Targeted interference of FOXO by resveratrol has already been demonstrated in lab animals and humans.
The red wine molecule resveratrol was recently reported to modestly modify cell-to-cell communication in the FOXO- β-catenin pathway among cells taken from patients with coronary artery disease. But the favorable effect, an increase (38%) in internal antioxidant activity (manganese superoxide dismutase) was achieved independent of β-catenin. [Iranian Journal Pharmaceutical Research 2016]
In the animal laboratory resveratrol has been demonstrated to selectively cause senescent cells to die off, a biological phenomenon called apoptosis (ap-oh- TOE-sis). [Journal Physiology 2014]
Resveratrol has also been demonstrated to counter cell senescence by its ability to summon the Sirtuin1 survival gene into action. [PLoS One 2015]
Finally, the ability of resveratrol to attenuate cell senescence via the FOXO3 gene, precisely the pathway suggested by de Keizer at Erasmus University, has also been demonstrated. [PLoS One 2015]
In the translation of the science surrounding the red wine molecule resveratrol from the animal laboratory to human use, three factors are to be considered:
Just how these facts get translated and confirmed from the animal lab into human use is difficult because conclusive evidence of longevity in humans would require a life-long study or at least a decade or two study beginning in the latter decades of life.
However, a recently published 30-day human study showed that resveratrol produced about the same blood concentration of Sirtuin1 gene protein as a calorie-restricted diet (up to 5.75 nanograms/milliliter for resveratrol, up to 5.80 for calorie restriction).
Resveratrol also significantly and beneficially altered insulin resistance. It appears the antioxidant activity of resveratrol helped to maintain higher resveratrol blood levels rather than increase synthesis of Sirtuin1 gene protein. [International Journal Cardiology 2017] Resveratrol has just taken another step forward in its confirmation as a calorie-restriction mimic.
A decade after David Sinclair at Harvard Medical School first announced a link between the red wine molecule resveratrol, lower mortality among individuals who consume resveratrol-rich wine and the activation of a survival gene (Sirtuin1) associated with life-prolonging calorie-restricted diets, The National Institute on Aging is finally in the recruitment stage of a study to determine cardiovascular effects of resveratrol among healthy adults. [Clinical Trials]
This is an example of science moving backwards. Usually lab dish experiments are followed by animal lab studies that precede human trials. Prior animal studies showed a given dosage range of resveratrol (not mega doses) when combined with other small molecules significantly exceeds the protective effect of plain resveratrol. There was ~40% less damage to heart muscle tissue when a synergistic matrix of resveratrol + quercetin + IP6 rice bran was utilized in an experimental model of heart attack. [Canadian Journal Physiology Pharmacology 2010; PLoS One 2010]