Resveratrol Helps The Heart Says New University Study
Resveratrol Keeps Hearts Young
June 4, 2008
Resveratrol, A natural compound found in red wine, may protect the heart against the effects of the aging process, researchers said on Tuesday.
In their study, mice were given a diet supplemented with the compound known as resveratrol starting at their equivalent of middle age until old age. These mice experienced changes in their gene activity related to aging in a way very similar to mice that were placed on a so-called calorie restriction diet that slows the aging process by greatly cutting dietary energy intake. Most striking was how the resveratrol, like calorie restriction, blocked the decline in heart function typically associated with aging, according to Tomas Prolla, a University of Wisconsin professor of genetics who helped lead the study. Much as Spaniard Juan Ponce de Leon once searched for the mythical fountain of youth, researchers now are seeking ways to extend the quality and length of human life. In some studies, animals given a diet with greatly reduced caloric intake have lived longer than animals with normal diets. But perpetual hunger is a steep price to pay for greater longevity, some researchers say. Resveratrol, found in abundance in grapes and in red wine, has drawn a lot of interest from scientists and some companies, including GlaxoSmithKline, which in April said it would pay $720 million to buy Sirtris Pharmaceuticals Inc, a company that is developing drugs that mimic the effects of resveratrol. Some studies have shown that in high doses, resveratrol extended the life span of fruit flies and worms and prevented early death in mice fed a high-fat diet. In this study, mice were given relatively low doses compared to the earlier research, and still experienced important aging-related benefits, the researchers said. The researchers began giving the resveratrol diet to the mice when they were 14 months old — their middle age — and followed the animals until they were about 30 months old. The researchers then conducted tests on cardiac function and on gene activity related to aging. “”Resveratrol at low doses can retard some aspects of the aging process, including heart aging, and it may do so by mimicking some of the effects of caloric restriction, which is known to retard aging in several tissues and extend life span,”" added Prolla, whose study was published in the scientific journal PLoS ONE. Using a method that permits simultaneous analysis of thousands of genes at the same time, the researchers found a huge overlap in the genes whose activity were changed by resveratrol and caloric restriction. They looked at the heart, brain and muscles, and said that the effect of resveratrol was strongest in the heart but did prevent some aging-related changes in the other tissues. Just because mice had these benefits does not mean people also would, although Prolla said, “”I think there’s a high likelihood that our findings are applicable to humans.”" He said he expected to see a lot of studies in the coming years on the effects of resveratrol supplementation in people.
Acetyl L-Carntine vs. L-Carnitine
The Essential Difference Between the Carnitines
Do you lack energy, or feel tired and physically or mentally unprepared to take on the tasks of the day? This is not unusual, especially as we age, and today’s topic may help explain some of the reasons for this energy deficit.
Two natural compounds produced by our tissues, L-carnitine and acetyl-L-carnitine (ALC), are similar in that both have identical chemical core structures. However, one (ALC) contains an extra component, an acetic acid bound to the core molecule (in what is known as an ester linkage). It turns out that this extra chemical piece makes a significant difference in how this molecule behaves in our body relative to its non-acetylated cousin, L-carnitine. These differences are described below, but first a brief summary of how these molecules normally function in our body.
L-carnitine functions as a vehicle to ferry fat constituents (fatty acids) across a membrane barrier into the cell’s energy-producing machine, the mitochondria, where the fat is converted to energy. Equally important, L-carnitine works in the reverse direction, too. It ferries toxic products produced during fat metabolism out of the mitochondria. This latter step helps maintain the mitochondria as clean-burning, energy-efficient machines.
We are all aware of the fact that as we age, our energy level diminishes. This decrease in energy parallels a decrease in the plasma level of L-carnitine. L-carnitine also decreases under conditions of stress, both psychological and physical. Consequently, it is described as a conditionally essential nutrient. This simply means that when our bodies cannot produce enough of it to meet demand, we need to increase the intake of this nutrient.
Acetyl-L-carnitine is just as active as L-carnitine in transporting fatty acids into the mitochondria. However, as described below, that extra acetyl group confers additional properties to this form of L-carnitine, which make it superior to its non-acetylated cousin. Both compounds increase energy Acetyl L-Carnitine or ALC Physical Energy Fat Metabolism Brain Protection Neurotransmission
Experiments with rats show a dramatic decrease (between 50-70%) in the activity level of old rats as compared to the young animal. Old rats, too, get tired with age! This decrease, as mentioned above, parallels a decrease in the amount of L-carnitine present in the animal’s tissues and blood.
This observation led researchers to investigate whether the old energy-deficient animals could be transformed into more energetic, youthful animals by feeding them a diet enriched with L-carnitine. Supplying L-carnitine to the diet increased the ambulatory activity of the old rats almost two-fold. The experiment was repeated with ALC, and it too increased the animals’ activity level to about an equal degree. So both compounds worked equally well in improving the old rats’ energy levels. ALC protects the brain
One of the two cousins, ALC, stands out with respect to its effects on the brain and nervous system. First, ALC is more effectively transported into the central nervous system. It more readily traverses the blood-brain barrier
Brain Cell Growth Boosted By DHEA Supplements
‘Anti-aging’ hormone DHEA Found to Boost Brain Cell Growth August 24, 2004
Human neural stem cells, exposed in a lab dish to the steroid DHEA, exhibit a remarkable uptick in growth rates, suggesting that the hormone may play a role in helping the brain produce new cells, according to a new study published this week in the online edition of the Proceedings of the National Academy of Sciences (PNAS).
The new work, conducted by a team of scientists at the University of Wisconsin-Madison, provides some of the first direct evidence of the biological effects of DHEA on the human nervous system, according to Clive Svendsen, the study’s senior author and an authority on brain stem cells at UW-Madison’s Waisman Center.
“What we saw was that DHEA significantly increased the division of the cells,” said Svendsen, a UW-Madison professor of anatomy and neurology. “It also increased the number of neurons produced by the stem cells, prompting increased neurogenesis of cells in culture.”
DHEA or dehydroepiandrosterone is among the most abundant naturally occurring steroids in the blood of young humans, but levels decline with age and its physiological effects are poorly understood.
A synthetic form of the hormone is sold over-the-counter as a dietary supplement in the US, thought to have anti-aging properties and to offer prevention against cancer and heart disease, Alzheimer’s and other diseases. But scientists know relatively little about the drug and its basic biological effects on humans.
“We don’t know much about DHEA, but this new work adds a piece to the puzzle,” said Svendsen, who conducted the study with colleagues Masatoshi Suzuki, Lynda S. Wright, Padma Marwah and Henry A. Lardy, all of UW-Madison. “This is the first real evidence of DHEA’s effects on human neural cells.”
Svendsen and Suzuki carried out the experiments by growing human fetal neural stem cells in culture. The cells form aggregates known as ‘neurospheres,’ which were exposed to a cocktail of DHEA and growth and inhibitory factors, and observed a 29 per cent increase in new brain cells compared to cells grown in a medium with the same factors, but without DHEA.
“We saw such a pure effect of DHEA,” Svendsen said.
“It’s the only steroid we tested that had such a direct effect on stem cell growth and new neuron formation,” according to Suzuki.
The new work is important because it provides a direct window to the controversial hormone’s effects on critical human cells. Similar studies have been conducted in mice and rats, but those models have shortcomings that are difficult to address, Svendsen notes.
“There are previous studies in rats that suggest DHEA is neuroprotective, but the problem with DHEA in rats is that it is not a major metabolite in that animal so its effects may not be the same as those seen in humans,” he said. According to Lardy, metabolic products of DHEA hormone have also been shown to aid memory retention in old mice.
Despite hints from the studies in rodents that DHEA may play a role in enhancing the brain and memory, the new findings reported in the PNAS article were a surprise, he said.
“We assumed the compounds we were testing would be more active than DHEA in brain stem cells,” Lardy explains. In previous studies, Lardy, with Wisconsin biochemistry colleagues James Ntambi and Brian Fox, showed that DHEA blocked a step in fat synthesis.
“The effects of DHEA on brain stem cells is a completely new finding,” said Lardy. “The problem of whether DHEA itself is having this effect, or if there’s another metabolite of the hormone involved, still exists.”
One of the intriguing aspects of the new work, according to Svendsen, is the possibility that DHEA could have some positive effects on the adult human brain.
It is known that DHEA amounts fall progressively during aging, and reduced levels of DHEA have been reported in both adolescents and adults with major depressive disorders. And given the fact that adult humans have neural stem cells that continue to make new neurons in some parts of the brain, there is a possibility that DHEA could play a role in moderating the genesis of new brain cells.