Research into pharmaceuticals that can extend life is ramping up. Some existing drugs are proving interesting.
In late 2014, a group of world renowned scientists in the study of ageing gathered in Toledo, Spain to discuss this very topic and they’re out to prove it can work. We’re not talking about those fictional stories of dialing back the clock to your twenties, coupled with all that learned wisdom that we’d like to do. This is research into putting on the brakes or at least slowing down the effects of ageing. The focus is mostly around age-related diseases and conditions.
Drugs that can delay ageing or stop some diseases from progressing or even starting, could add many healthy years to a person’s life. That has social and economic benefits, including reducing the burden on health care and enabling people to live more productive lives longer.
One such hot drug is the type 2 diabetes medication, metformin, followed by the chemotherapy and immunosuppressant drug rapamycin. Scientists also are studying a class of compounds known as senolytics, which attack “senescent” cells in the body that tend to proliferate with age. Senescent cells damage healthy cells around them, contributing to multiple age-related diseases.
The challenge for these drugs though is that in Canada, ageing is not considered a disease, just as in the United States and United Kingdom, making getting approvals that much more difficult. The first approach these scientists are taking is with metformin to study if it has a significant role in reducing dementia, heart disease and cancer.
One recent study caught their attention around metformin when they noticed that diabetics who took the medication outlived non-diabetics who didn’t. Also metformin showed an effect in other, separate studies against each of the above diseases. Now the scientists are conducting one large, randomized controlled clinical trial.
The study is called Targeting Aging With Metformin (TAME) and will be based on a study of 3,000 subjects aged 65 to 79 across 14 research sites. A main reason for choosing metformin is that it has a long track record, it’s safe and inexpensive.
These scientists want government agencies like Health Canada and the Food & Drug Administration (FDA) in the U.S. to start considering treatment for ageing in the context of prevention, rather than just defined diseases. This is a shift in thinking for these organisations and they tend to be slow, so many studies will be needed and lobbying them to think differently.
Says Steven Austad, in a recent interview with The Washington Post, who chairs the biology department at the University of Alabama at Birmingham and is senior scientific director of the American Federation for Aging Research. “But the fringe benefit is that you live longer.”
“The FDA and the drug companies need to see a pathway to approval,” Austad says. “The reason Big Pharma has never been interested in anti-aging is because [such a study] would take 50 years. We came up with research that could provide some answers in five or six years.”
Metformin works on several metabolic process that are linked to aging such as inflammation, waning chromosome repar and immune dysfunction. It also improves the efficiency of our mitochondria, which are the “powerhouses” within the body’s cells that drive our breathing and energy.
Scientists think as well, that metformin might influence the enzyme controlling our body’s energy by mimicking the effect of a low calorie diet. Many doctors believe that reducing caloric intake helps in improving life extension. “Aging occurs in multiple biochemical pathways — it’s not just one thing,” Austad says. “Metformin has multiple targets, which might make it the best thing in the world for aging.”
One other study underway with metformin is looking at if it can help prevent frailty, which is a cluster of symptoms affecting the elderly. People who are frail tend to suffer from several symptoms that include weight loss, muscle loss, fatigue and low levels of physical activity. Frailty can lead to disabling falls and sometimes death.
Research is also underway using rapamycin, which has shown strong indications of benefits in anti-ageing in mice, but has yet to be tested on humans for this purpose. Rapamycin works by inhibiting a gene that gets turned on after meals but is turned off, or down, with fasting. Research has shown that fasting makes laboratory rodents live longer lives. No human study has yet been set up with this drug, but it likely will be.
Then of course, there’s senolytic drugs. These medications attack senescence, a condition that happens when some cells in the body become damaged over a life-time. They stop dividing, impairing the body’s ability to replace old and injured tissue.
Senescent cells secrete proteins that are inflammatory that destroy or harm the healthy cells around them. The resulting diseases include dementia, strokes, cardiovascular diseases, arthritis and metabolic diseases.
Studies in mice have demonstrated that senolytics reverse cell damage wrought by senescent cells, and extend life. Recently, they also have shown promise in humans. More than a dozen clinical trials are underway testing different combinations of these drugs.
This all much needed and powerful research, but it’s not at the stage where you can run off to your doctor and ask for any of these drugs for these purposes just yet. Researchers need to understand side-effects and other risks and ensure that the benefits outweigh the potential risks. But it is promising.
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