Diets that purport to slow the aging process are becoming increasingly popular.
Their proponents cite evidence that nutrient-restricting diets can increase healthy lifespan â€” at least in laboratory organisms such as yeast, worms, flies, and rodents.
For some people with a particular genetic makeup or under certain environmental conditions, the diets may actually be detrimental to health.
The reviewers emphasize that there are no clinically proven anti-aging diets and conclude that more research is needed before doctors can recommend such diets for otherwise healthy people.
By contrast, the enormous variations in human environments and lifestyles are likely to have a large impact on the health effects of potential life-extending diets. Genetic variation between individuals is also likely to play a role in the dietsâ€™ outcomes.
Another problem with translating the promising results in animal studies into humans is that our lives can span decades, whereas theirs only last a few years. Comparable studies in humans would take many years to complete.
Risks and benefits
Extreme calorie restriction â€” which animal research suggests is likely to yield the greatest life extension â€” also comes at a cost.
We know from the relatively small number of people who manage to conform to such rigorous diets that potential side effects include:
- poor cold tolerance
- loss of libido and sexual function
- psychological problems
- chronic fatigue
- poor sleep
- muscle weakness
- increased susceptibility to infection
- impaired wound healing
â€œ[S]evere [calorie restriction] can impair both immune function and wound healing, which could offset any potential lifespan-extending benefits under adverse environmental conditions in which the immune system is challenged, for example, a global viral pandemic, or in the absence of quality healthcare.â€
There is some observational evidence that less extreme calorie restriction can yield significant benefits, however.
For example, the inhabitants of the small Japanese island of Okinawa traditionally consume 20% fewer calories than people who live on the mainland.
In the past, residents of Okinawa have enjoyed the longest life expectancy and the highest number of centenarians per head of population anywhere in the world.
Research suggests that they also experience exceptionally low rates of age- related illnesses, including cancer, cardiovascular disease, and diabetes.
However, as with all observational studies, the research cannot establish whether calorie restriction is responsible for these health benefits.
While no clinical trial has tested whether there is an increase in overall lifespan with calorie restriction, a series of shorter trials lasting from a few months to 2 years have found clinical benefits that are likely to extend a healthy lifespan.
The studies have found that a 25% reduction in calorie intake is associated not only with decreased weight but also enhanced insulin sensitivity and glucose tolerance and improvements in risk factors for cardiometabolic disease.
But they go on to say that the animal findings are â€œhighly suggestiveâ€ that ketones could have anti-aging properties.
There are many variations of fasting diets, but they fall into three broad categories:
This is because the animals in the experimental group usually end up consuming fewer calories than animals in the control group.
So itâ€™s difficult to distinguish the potential benefits of fasting from the well-established benefits of calorie restriction.
But the reviewers do point to a study that compared mice allowed to eat only on alternate days with mice that consumed the same overall calories but without fasting.
This study found improvements in metabolism and reduced inflammation in the intermittent fasting group.
However, an equivalent study in people found that individuals who fasted every other day saw fewer benefits for their health than individuals who simply ate a calorie-restricted diet with the same overall energy intake.
The results for time-restricted fasting from animal and human studies are similarly conflicting.
The reviewers cite studies in rodents that found time-restricted fasting improved various measures of metabolic health and protected against an obesogenic or obesity-causing diet.
But research in humans has yielded mixed results for time-restricted fasting. Some studies have shown only mild improvements in health, whereas others have suggested detrimental effects on glucose metabolism.
Protein and amino acid restriction
They report that while protein restriction in itself increases lifespan, the benefits are considerably weaker than those from calorie restriction.
Animal studies suggest that restricting tryptophan, methionine, leucine, valine, and isoleucine is beneficial for increasing a healthy lifespan.
A universal aging switch
Intriguingly, nutrient-restricting diets appear to increase longevity and reduce age-related disease through their effect on a small number of metabolic pathways.
Specifically, the diets tend to reduce levels of growth hormone, insulin-like growth factor, and a signaling molecule called mechanistic target of rapamycin (mTOR).
Research in nematode worms and yeast shows that these molecules are key hubs in a molecular mechanism that senses the availability of nutrients in the animalsâ€™ environment.
The job of this mechanism is to promote cellular maintenance and repair when nutrients are scarce but redeploy the organismâ€™s resources towards reproduction when nutrients are plentiful.
According to the disposable soma theory, this mechanism reflects the trade-off that all organisms â€” from yeast to people â€” have to make between staying alive and reproducing.
The existence of a nutrient-sensing mechanism that controls aging raises the exciting prospect of targeting it with a drug to promote longer, healthier lives.
It remains to be seen whether the drug would combat aging to the same extent in humans, who already enjoy relatively long lifespans.
Prof. Kaeberlein studies aging in lab animals and pet dogs at the University of Washington.
â€œItâ€™s early, but there are hints that itâ€™s possible to tweak the network with rapamycin in older dogs and people to potentially achieve similar functional benefits in the heart and immune system as what is seen in mice,â€ he said.
â€œWhether that will translate through to healthspan more broadly or lifespan or not, we donâ€™t know yet, but I think we will get that answer in the next 5â€“10 years.â€â€“ Prof. Kaeberlein
Doctors give high doses of the drug, which modulates the immune system, to prevent rejection in organ transplant patients.
At these doses, side effects are severe, though proponents of rapamycin as an anti-aging drug claim that the benefits outweigh the costs at lower doses.
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