Resveratrol is Weak Medicine, and It's Well Past Time to Move On
There is a very simple measure for any new potential therapy for enhanced longevity: is it either (a) doing at least as well as calorie restriction in mice when it comes to health and longevity, or (b) achieving important results that calorie restriction cannot show in mice - such as outright rejuvenation. The popular supplement resveratrol fails miserably to achieve significant results in either of these goals after more than five years of experimentation and hundreds of millions of dollars in research funding. This means that it is a dead end, or so close to one as makes no real difference. The only value gained lies in incremental improvements in the understanding of metabolism - which could have been achieved while studying more effective paths to the same end goal.
Resveratrol and life extension
Age is the most important risk factor for diseases affecting the Western world, and slowing age-related degeneration would greatly improve the quality of human life. In rodents, caloric restriction (CR) extends lifespan by up to 50%. However, attempts to mimic the effects of CR pharmacologically have been limited by our poor understanding of the mechanisms involved. SIRT1 is proposed to mediate key aspects of CR, and small molecule activators may therefore act as CR mimetics.
The polyphenol resveratrol activates SIRT1 in an in vitro assay, and produces changes that resemble CR in vivo, including improvements in insulin sensitivity, endurance, and overall survival in obese mice. However, resveratrol has numerous other targets that could contribute to its health benefits. Moreover, unlike bona fide CR, resveratrol has not been shown to extend lifespan in lean mice.
Whenever a new supplement, drug, or something else you can put in your mouth is announced to possibly affect longevity, there follows a breathless wave of hype and money-making. Go search for "resveratrol" to see the present pointless wasteland of thoughtless buyers and manipulative sellers. You'd think that no-one has a memory of longer than a year: every time this happens exactly the same way, and in the end it all comes to nothing.
Silver bullets don't exist, and the future of longevity science will not be found in paths that fail to show immediate, exciting benefit in mouse studies. When there are multiple ways to extend mouse life span by 50%, why would anyone be worked up about about something that fails to move the needle at all? It's way past time to move on from the resveratrols of the world and focus on research and development that can have a positive effect on the future of human longevity.
Mr. Reason keeps pushing high-tech answers that society simply cannot afford. Resveratrol research continues and one wonders where all the human research is? Human clinical research is wanting. Resveratrol is being dismissed by Big Pharma because this single small molecule threatens modern pharmacology. Resveratrol would replace most prescription drugs. Rapamycin is posed as the next anti-aging pill, but it could not possibly be employed among the healthy because of its many side effects.
There certainly is truth to the hucksters who sell res pills, and there is truth to the issue of magic bullets. But modern medicine has few of those as well and cancer, hypertension, heart disease and most other age-related disorders are treated with multiple drugs. Single molecules rarely work.
The same goes for resveratrol, its real power is when it is combined with other small molecules and this has been demonstrated in numerous studies. The magic of red wine is that it concentrates by fermentation a number of small molecules that work synergistically.
It is important to first develop a theory of aging rather than be left with the nebulous library of 300 posed theories of aging. Why do humans age? So much research is conducted without addressing that.
Humans age at three different speeds, as evidence by the accumulation of lipofuscin -- cellular debris that is not digested away by enzymes produced by lysosomal bodies within living cells. There is, in general, little or no accumulation of lipofuscin during the growth years, then progressive accumulation during the following middle years, and then a slowing of the rate of aging in late life. The only explanation for this is overmineralization. The demand for minerals is high during childhood growth. Minerals, primarily iron, copper and calcium, begin to accumulate in excess after childhood growth of completed. The lysosomal bodies and mitochondria within calls begin to rust and calcify.
Males age faster than females. By age 40 a male has twice as much iron and four-times as much calcium as an equally-aged female, and incurs double the rate of cancer, diabetes and heart disease. Females live, on average, 5-8 years longer than males. Women avoid overmineralization by donating minerals to their offspring and dumping iron and copper via monthly menstrual flow. If a woman has an early hysterectomy, she has the same rate of disease as males.
Resveratrol is a copper-chelating molecule that also controls iron via production of heme oxygenase. Resveratrol inhibits calcification of tissues and loss of bone by stimulation of osteocalcin, the hormone that holds calcium in bone instead of its typical loss with advancing age and subsequent calcification of arteries and soft tissues.
There currently is evidence that resveratrol, and more so resveratrol when combined with other small molecules, turns mortal heart attacks into non-mortal events. This has been demonstrated in excised animal hearts and cannot be repeated in humans for obvious ethical reasons. There is strong evidence that resveratrol combats cancer at all three stages of development -- initiation, growth and spread (metastasis), something no other anti-cancer drug can claim. I have evidence in hand that a resveratrol-based nutriceutical completely reverses a rapidly-progressive form of blindness in aged adults and rescues stem cells in the process so that tissue regeneration is experienced.
There -- you have been presented with the fact that resveratrol potentially erases mortal heart attacks, prevents cancer and reverses an age-related form of blindness, three scourges of mankind. Is this good enough for you?
In an ignored study conducted over 15-years ago it was shown that CR dramatically reduces accumulation of lipofuscin in the retina. But it was also shown that bran added to the diet of animals produces almost the same effect. Bran contains a mineral-controlling molecule. [Investigative Ophthalmology Vision Science November 1993 vol. 34 no. 12 3297-3302] This study provided early evidence that there are ways to mimic CR molecularly without the need for food deprivation.
Great article posted by Bill Sardy where is unmasked the dirty market driven by Big Pharma for the purpose of accumulating profit regardless of the real wellfare of humanity.Congratulations Bill!!
IIRC, the early first resveratrol findings on yeast life span where accompanied by human in-vitro studies. Cell survival upon exposure to gamma radiation was tripled, again iirc. Humans are not as vulnerable to cancer as mice are, so the results in mice need not necessarily apply to humans, especially high cancer resistance individuals(individuals able to tolerate high carcinogen levels in the environment without developing cancer).
Yessir: That's a heck of an hypothesis! All mechanistic speculation, of course -- but what the heck: let's run a lifespan study in healthy, normal rodents to see if it actually pans out!
Oh -- wait ...
There isn't a magic bullet for long life. But there is one for a happy life. "helping others" There are numerous studies showing that it may not extend your life, but it could help your liver, fat around your waist line, and help spinal disks and joints regrow. I may not live forever but I would like to keep the above healthy~
I think it is unwise to dismiss resveratrol as useless in providing health benefits, if not enhancing longevity. Perhaps, the reason why resveratrol is not replicating the in vitro effects in vivo may be because of NAD. It has now been established that NAD declines with age and NAD is a co-factor for Sirtuin. David Sinclair has recently shown that just providing NAD (via non-pharmacological dose of Nicotinimaide mononucleotide) can provide some reversal of muscle disfunction in aged mice. There is at least some basic evidence that activating resveratrol alone may not lead to restoration of the function of Sirt 1. Quite possibly NAD is also required. Only a clinical trial of resveratrol with an NAD precursor may answer this question whether activating sirtuin with resveratrol would have meaningful benefit.