Dr Sinclair

Dr. Sinclair and his research team in medical department of

 Harvard University announced “ Resveratrol provides excellent

 anti cancer, anti aging, cell regeneration… “

                      21st   不 老 長 生 物 質 “




How Long Shall Humans Live? The Current Answer Is Found in a Glass of Red Wine

by Bill Sardi
by Bill S

As I entered the Harvard laboratory, it was inauspicious. The myriads of glass flasks and laboratory work benches were arranged in a haphazard fashion. One wonders what could come out of all this biochemical chaos? But this lab has gained unusual attention in the past few weeks, and its discoveries are sure to affect the future of mankind.



David Sinclair, PhD, Harvard genetic scientist has found how to turn a survival gene into a longevity factor.

The laboratory I am talking about is the Sinclair Lab, named after Dr. David Sinclair, a pathology professor at Harvard Medical School.

David Sinclair is a young, smiling, bio-genetic researcher whose passion has been the study of aging. A native of Australia, he came to the USA to do research work at MIT and Harvard noticed his accomplishments and lured him with his own laboratory, now housed in Goldensen Building at Harvard Medical School.

Up till now, the only unequivocal method of prolonging life has been calorie restriction. The prospect of a near-starvation diet is obviously a difficult idea to market to human populations. So the announcement of Sinclair's research is being met with glee.

Sinclair has been interviewed by every major news network in recent weeks for his discovery, published in Nature magazine, that a dietary component could lengthen the human life span by 70 percent, up to 50 years. A 125-year human lifespan could become common! Even an older adult could live years longer by increasing dietary resveratrol intake.

A survival gene becomes a longevity factor

What Sinclair and his students have uncovered is a survival gene that can be "switched on" to become a longevity gene. The gene increases the production of an enzyme that prolongs the time a living cell has to repair its DNA genetic material. This enzyme is normally produced when the survival of living cells is threatened by starvation, exposure to germs or bombardment by solar ultraviolet radiation. No longer would humans have to starve themselves to prolong life.

In a plant model, the skin of a grape increases its production of the enzyme which produces a protective molecule called resveratrol. It is resveratrol, when given to yeast cells, fruit flies, worms and mice that extends life by a whopping 70 percent. Humans have the similar survival gene.



Pinot noir grapes contain more of a newly found longevity factor than other types of grapes.

There has been a flurry of scientific reports on resveratrol recently. About 450 of the approximately 750 scientific reports on resveratrol listed by the National Library of Medicine have been published in the past 24 months. Studies point to this miraculous molecule as a potential cure for cancer, heart disease, age-related brain disorders, and much more. Resveratrol inhibits fungal infection, raises HDL "good" cholesterol, lowers PSA levels in males, raises immunity, controls blood pressure, preserves red blood cells, prevents blood clots and inhibits inflammation. How much more could one ask of one molecule? Furthermore, it would take only about 3 to 5 milligrams of resveratrol, about the amount provided in a glass of red wine, to produce these results in humans.

The future of resveratrol

During my two-hour interview with Dr. Sinclair, I asked him what he had in mind for the future of this molecule. He said that venture capitalists had the idea of taking artificial copies of resveratrol, called analogs, and making them expensive drugs. But they were disappointed when his laboratory disclosed that the same molecule could be acquired in a glass of red wine. A resveratrol drug would probably take a decade to develop and get approved by the Food & Drug Administration, added Sinclair.

Dr. Sinclair says the public needs to know more about this remarkable natural molecule and how to get more of it into their diet. It could be as simple as drinking a 5-ounce glass of red wine, preferably from pinot noir grapes grown in northern latitudes like New York, Oregon and Washington, that generally yield more resveratrol than other varieties.

Challenging resveratrol

Of course, Sinclair's research is so unbelievable that it required some further challenges. Why aren't everyday imbibers of red wine centenarians? Why can't people just drink grape juice, or eat raisins, or grapes for that matter, and live longer? The answer lies in the wine-making process. The fermentation process extracts resveratrol from the skin of a red or purple grape and then it is kept from spoilage in a nitrogen-flushed bottle. The air doesn't get to the resveratrol in a bottle of wine so it can't oxidize. Grape skins provide resveratrol, but not in an extracted form. Due to processing, grape juice provides little resveratrol. Sun-dried raisins also contain no resveratrol due to oxidation by sun rays. The same is true for resveratrol pills which are widely marketed. Their resveratrol content, extracted from the Giant Knotweed plant (also called fo-ti in Asian cultures) for use in dietary supplements, is nil. Sinclair has tested a number of brands of resveratrol pills and their resveratrol content was zero. The resveratrol disappears soon after exposure to air during encapsulation. For now, red wine is the only reliable source of resveratrol. White wine has ten times less resveratrol.

What will humanity do?

What will humanity do with a molecule that can repair damaged DNA, abolish age-related disease as we know it and prolong human life by decades? Who will pay the Social Security payments up to age 125? How will insurance companies re-calculate actuary tables? Can you get a refund on your long-term care (nursing home) insurance if you don't need it? After all, a great deal of planning goes into the assumption human beings will die on time, in their seventh or eight decade.

Dr. Sinclair says the world will need to adjust accordingly to discoveries such as resveratrol. This kind of discovery can't be hidden. Just imagine, Sinclair said, what people could have said after Alexander Fleming announced his discovery of penicillin in 1922. At the time, nay-sayers could have claimed that penicillin would eradicate infectious diseases and dramatically expand human populations, resulting in famine and war. Why not let the concept of "survival of the fittest" reign?

Thomas Malthus issued his doomsday theory on population growth in 1798 which meant any dramatic increase in survival would doom humanity to overpopulation, scarcity of food, and eventual massive trimming of the size of the world's human populations. But Malthus couldn't foresee the industrial revolution or modern methods of crop production. Similarly, the availability of a stabilized resveratrol plant extract, now underway, could also be used to increase human food supplies. For example, dipping apples in resveratrol preserves their freshness for weeks following harvesting. Resveratrol may have use as a novel food preservative, thus remedying a social problem of its own creation.

The word resveratrol is soon to become widely known. Millions will benefit from its availability. The introduction of a non-alcohol dietary supplement that can reliably deliver standardized amounts of resveratrol to human populations would certainly cause a stir throughout the world. No date has been given in regards to the introduction of such a product, but it is reported to be beyond the drawing board stage. Dr. Sinclair is the genie who is unleashing this molecule and future reports on his work will only substantiate what has already been documented.

September 18, 2003



Wine may extend human lives

By Amanda Anthony
Assistant Campus Editor

Red wine has long been known to reduce heart disease as part of the "French Paradox," but a new study shows that one compound in red wine may actually prolong the human life span.

The natural compound used in that study, resveratrol, was discovered by John Pezzuto, dean of the Purdue School of Pharmacy, when he was a professor at the University of Illinois-Chicago. Although it was discovered in a non-edible legume in the South American rainforest, Pezzuto found that it could also be induced by stress into the skins of red and white grapes.

"Under sterile conditions, there's no resveratrol," he said. "Grapes have to be put under stress to produce it."

Pezzuto describes resveratrol as a phytoelexin, a compound that protects the plant from damage. It is present in large amounts in red wine because of the fermentation process used to make it.

"Because the compounds in the skin undergo a longer fermentation, they are leached into the wine," he said. "White wine is produced by a quick compress," resulting in less resveratrol present.

Pezzuto said that the effects of the compound are not the same as those of the "French Paradox," a phenomenon in which French people have fewer physiological problems and less heart disease despite consumption of richer foods and more cigarettes than Americans. French people also tend to drink one or two glasses of wine a day, something that scientists have used to explain the paradox even though they don't know the mechanism.

Still, resveratrol may be contributing to those benefits, especially in terms of chemoprevention. Pezzuto has already shown it to be effective in preventing skin and breast cancer while other researchers showed its effectiveness in preventing colon cancer. A recent study out of Switzerland shows that it may prolong life, too.

Dr. David Sinclair of the Harvard Medical School published a paper in Nature that indicates resveratrol extends life in yeast by 70 percent.

In the study, resveratrol was designed to mimic the effect of a low-calorie diet, which has been shown to lengthen the life of rats and mice — something scientists hope applies to humans.

Although resveratrol has not been proven to extend life in humans, scientists involved in the study told The New York Times that human life spans could be extended by as much as 30 percent if humans respond to the chemicals in the same way as rats and mice do.

Sinclair said the research is promising but still 8 to 10 years away from having an approved drug.

Pezzuto said one Canadian company is synthesizing the compound on a large scale to market as a dietary supplement but he said more clinical studies need to be done to see how effective resveratrol is alone as well as part of wine.

He ran one study where people drank two glasses of red wine a day with no clear-cut effects on cancer. One-third of the subjects showed decreased cancer risk, one-third were more likely to get cancer and the last third had no effect.

"It can't be interpreted properly," he said. "But it still has promise — if not resveratrol itself, then some chemical derivative."



Fruit Extracts Offer Hope in Skin Cancer Prevention

October 30, 2003

Common fruits not only contain a number of vitamins and minerals that help fight everyday illnesses but could also harbour agents that can reduce the risk for skin cancer, suggests new research presented this week at the Frontiers in Cancer Prevention Research meeting.

Researchers from the University of Wisconsin reported that a pomegranate extract inhibited skin tumours in mice, while the red wine compound reseveratrol, applied topically, inhibited the expression of a cancer-causing protein normally caused by exposure to UVB rays.

"We are pleased to see numerous studies exploring the therapeutic value of topically-applied natural ingredients that people can begin incorporating into everyday life and may enhance the activity of standard sunscreens," said Dr David Alberts from the University of Arizona.

Incidence of skin cancer, which is the most frequently diagnosed malignancy in the United States, is also growing rapidly in Europe. In the UK, melanoma accounts for 2 per cent of all newly diagnosed cancers each year. Among people under 35, it is the third most common cancer in women and fifth most common in men.

Pomegranate fruit extract (PFE), from the tree Punica granatum, contains several polyphenols and anthocyanidins (pigment that gives certain fruits their dark red colour), which demonstrates a higher antioxidant activity than that of red wine and green tea, according to the Wisconsin researchers.

The team evaluated pomegranate's anti-skin tumour effects by comparing topical application of pomegranate extract on neonatal mice (CD-1) against TPA-induced markers (12-0-tetradecanoylphorbol-13-acetate), a strong promoter of chemically induced skin cancer. Applying pomegranate extract (2 mg/mouse) onto the skin of neonatal mice 30 minutes prior to TPA (3.2 ole/mouse) application significantly inhibited TPA-mediated increases in skin edema and hyperplasia, they said.

They also tested the pomegranate extract on TPA-induced skin tumour promotion. The animals pretreated with pomegranate extract showed substantially reduced tumour incidence and lower tumour body burden. In the TPA treated group, all mice developed tumours at 16 weeks, whereas only 30 per cent of the mice treated with pomegranate extract exhibited tumours at that point.

"For the first time, we have clear evidence that pomegranate extract possesses anti-skin-tumour-promoting effects," said Dr Farrukh Afaq, lead investigator of the study.

He added: "With such a variety of pathways inhibited by the topical application of the natural supplement, we are confident of its therapeutic value and hope it will translate to other models."

According to the researchers, because pomegranate is capable of inhibiting conventional as well as novel biomarkers of TPA-induced tumours, it may possess chemopreventive activity in a wide range of tumour models. The researchers plan to carry out an in-depth study to define its active agents.

A second study presented at the conference (abstract 1489) examined the effect of resveratrol, an antioxidant found in grapes and red wines, on UVB-related skin damage. Researchers evaluated the effect of topical application of resveratrol (10 ole/mouse/0.2 ml acetone) on multiple UVB (seven consecutive exposures in seven days) exposure-mediated damages in the skin of SKH-1 hairless mice.

The study evaluated resveratrol's influence on survivin, involved in the control of cell division, and a structurally unique member of the apoptosis inhibitors protein family. Survivin is overexpressed in most human cancers, but absent in normal adult tissues, and is considered a promising therapeutic target for novel anticancer therapies. Results of the study showed that resveratrol treatment significantly decreased UVB exposure-mediated up-regulation in the mRNA levels and protein expression of survivin.

"We're pleased to see that resveratrol is able to modulate multiple signaling in the cells, which actually protects the skin cells from damages that may lead to the development of cancer," said Dr Nihal Ahmad, of the University of Wisconsin, and lead author of the study. "Further study should continue to support the argument to incorporate this agent into skin care products and regular diets, through the moderate consumption of grapes and red wine."

Resveratrol significantly inhibited UVB-mediated increases in skin thickness and edema; epidermal cyclooxygenase (COX-2); ornithine decarboxylase (ODC) enzyme and protein levels; and protein levels of proliferating cell nuclear antigen (PCNA), all of which are established markers of tumor promotion. Resveratrol also further stimulated a UVB-mediated increase in p53 protein levels and was found to inhibit UVB exposure-mediated increases in cell cycle promoting signals including the activation of cell division.

Dr Alberts noted the need for promotion of such research. "The incidence of skin cancer is rising faster than any other solid tumour in the United States. It is critical that we develop novel approaches to both primary and secondary prevention of what appears to be becoming an epidemic."