Estrogen is a steroid hormone that both males and females produce naturally. It is famous for regulating reproduction, but it also protects against some diseases of aging, such as type 2 diabetes, osteoporosis, metabolic syndrome, and Alzheimer’s disease.
Research by Henry Bayele, Ph.D., a molecular biologist at University College London in the United Kingdom, suggests that in small amounts, resveratrol — which is in peanuts, pistachios, the skin of grapes, red wine, blueberries, raspberries, and even cocoa and dark chocolate — may reproduce these health benefits.
His in vitro study of human liver cells found that the compound exerts its physiological effects by activating receptors for estrogen.
The activation of estrogen receptors switches on proteins called sirtuins, which play a wide variety of roles in healthy aging. These roles include controlling mitochondrial biogenesis, promoting the repair of DNA, and regulating metabolism.
Biologists view sirtuins as excellent potential drug targets because they protect against several conditions associated with aging, including obesity, type 2 diabetes, cancer, cardiovascular disease, and neurodegenerative diseases.
“Numerous studies in animals have suggested that these proteins could prolong healthy lifespan by preventing or slowing disease onset,” says Bayele. “But developing effective drugs or dietary interventions has been frustrated by a lack of a common understanding of how exactly they work in the body’s cells.”
Less is more
To find out more, Bayele exposed liver cells to a variety of dietary compounds that activate sirtuins. These included resveratrol, as well as isoflavones, such as daidzein, which is in soybeans and some other legumes.
The compounds are collectively known as dietary sirtuin-activating compounds or dSTACs.
Bayele discovered that at low doses, resveratrol increased sirtuin signaling in the cells by mimicking estrogen. However, at high doses, it reduced sirtuin signaling.
This finding supports the idea that just a small glass of red wine a day, and no more, can promote healthy aging. Other dietary components may work just as well.
For instance, Bayele found that a dSTAC called isoliquiritigenin, which is present in licorice, is even better than resveratrol at activating sirtuins.
The study findings feature in the journal Scientific Reports.
According to Bayele, his research suggests that people could view dSTACs as “plant estrogens.” They may benefit the brain, liver, skeletal muscle, and bone by performing functions that would usually be the preserve of estrogen.
In theory, this could lead to the development of alternatives to hormone replacement therapy (HRT) for counteracting the symptoms of menopause.
HRT increases the risk of stroke, heart attack, and certain types of cancer.
However, Bayele stresses that clinical studies will be necessary to confirm whether people can use dSTACs as estrogen substitutes to promote healthy aging.
In the paper describing his work, Bayele notes that the findings may help explain the “French paradox.”
This term refers to the observation that despite eating a high fat diet, some populations in France experience low rates of cardiovascular disease and certain types of cancer.
Scientists have proposed that this may have something to do with the French fondness for regularly consuming red wine — but always in moderation.
However, Bayele cautions that the effects of dSTACs on cells in vitro may not reflect their effects in people.
For example, the body may digest the compounds in the gut, or the intestinal microbiota may metabolize them. Even if they survive digestion intact, the absorption of these compounds into the bloodstream may be poor, or the liver may break them down.