Researchers have been looking at our eating habits, what we eat, when we eat, and how much we eat for many years to see if they can help us avoid age-related diseases like heart disease, diabetes, and dementia. They also desire to know more about how different eating habits might affect the health of our musculoskeletal system, which is made up of our muscles, bones, and connective tissue.
Researchers are especially interested in calorie restriction, which means cutting your average daily caloric intake below normal without becoming malnourished or missing out on important nutrients. You can also cut calories by not eating for a few hours or days, called “intermittent fasting,” or by eating less at some or all of your meals. Some studies with animals and people have shown that limiting calories can improve many health problems. It also makes many animal species live longer, but there is no proof that this is true for people.
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What Research Supports Calorie Restriction Mimetics?
Researchers are considering that limiting calories helps people live longer and healthier lives by changing one or more biological pathways important for healthy aging. Biological pathways are chains of chemical reactions that happen inside the body’s cells. They are like a factory’s production line. It’s like a set of instructions with steps that must be done to do something. For example, activity along a biological pathway could lead to the formation of a new cell, the destruction or repair of an injured cell, the movement of a signal along a nerve, the production of a hormone, or the turning on of a gene to activate another pathway.
Calorie Restriction Mimetics Research: Key Biological Pathways
Most of the research on calorie restriction mimetics is focused on four biological pathways:
Insulin signaling pathway. When you eat, your body turns the food into glucose, which is used for energy. When glucose is in the blood, a hormone called insulin is released. Whether glucose is used right away or stored, and where it is stored depends on how insulin tells the body what to do. If the signals along this pathway don’t work right, it can lead to problems with how glucose is handled and diseases related to aging, like diabetes and heart disease.
Pathway of the mammalian target of rapamycin (mTOR). When nutrients are available, the mTOR pathway can tell. When it sees enough nutrients, it tells the cell to grow. When there aren’t enough nutrients, which happens when you cut back on calories, the mTOR pathway tells the cell to prepare for stress. This makes it easier for the cell to fix itself and fight toxins and other problems.
Sirtuin-1 (SIRT1) pathway. Sirtuins are a group of enzymes that help control metabolism and keep cells healthy. They can make more mitochondria, which are the powerhouses of cells. SIRT1 is the sirtuin that has been studied the most. Signaling along the SIRT1 pathway helps cells resist stress and stay alive.
AMPK pathway. AMPK is an enzyme that helps keep cells stable by starting reactions that help cells use energy more efficiently.
Which Chemicals Excite Researchers the Most About Mimetics?
Scientists are researching a wide range of drugs and experimental chemicals to investigate whether they have effects comparable to calorie restriction based on a current understanding of important biological pathways (see box above). Pharmaceuticals, nutraceuticals (compounds found in food), plant extracts, and substances made by the body, like hormones, peptides, and amino acids, are all things that are studied.
Resveratrol is a chemical found in nuts, dark chocolate, blueberries, raspberries, red wine, and grapes. It gets SIRT1 and the other sirtuin pathways going. Animal studies have shown that resveratrol has anti-inflammatory, anti-cancer, and antioxidant effects. Human studies, on the other hand, don’t show much. For example, in the Aging in the Chianti Region study, which was paid for by the NIA, researchers tracked 783 healthy people for 9 years and measured how much resveratrol they ate. The study found no link between taking resveratrol and being healthy or living longer.
Calorie Restriction Mimetics Animal Research Funded by the NIA
The NIA’s Interventions Testing Program (ITP) tests oral treatments on mice to see how they affect disease and how long they live. The results of these studies help scientists find the most promising treatments to test on animals and, in the long run, in people in clinical trials that check for safety and effectiveness. So far, the program has found the following about calorie restriction mimetics:
Even when rapamycin was given to old mice instead of young mice, it still made the mice live longer. This means that some compounds might be worth looking into for use in the future.
When metformin was given along with rapamycin to female mice, the side effects of rapamycin were lessened. This finding shows that more research must be done on working drugs.
When male mice were given rapamycin and metformin together, the side effects were not lessened. Researchers have also found that aspirin, estrogen hormones, and NDGA, which could mimic, have different effects on male and female mice (an extract from the creosote plant). We need to do more study to determine why some effects may differ for men and women.
When mice were given curcumin, green tea extract, and fish oil, there was no clear evidence that they lived longer. If these substances affect health, more study is required to determine what those effects could be.
What Role Will Calorie Restriction Mimetics Play in Health Care?
If and when it is shown that calorie restriction mimics can make people live longer, they will probably be most helpful for people who are sick and can’t eat well. People in good health may be able to stay healthy longer by doing things that are good for them than by taking medicine made from research on mimicry. This includes eating nutritious meals, exercising, consuming alcohol in moderation or abstaining entirely, avoiding smoking, having a decent night’s sleep, and keeping an active, social lifestyle.
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