Calorie restriction has a large beneficial effect on health and longevity in mice, and as a result any number of studies carried out over the past century were ruined - usually without the researchers noticing - because no attempt was made to control for calorie intake and weight. Any treatment that causes nausea in mice, and thus a lower calorie intake, may have mistakenly reported benefits. Any treatment that resulted in mice eating more may have mistakenly missed benefits or reported harms.
The same general principle applies for people running their own self-experiments of treatments that might slow or turn back aging to some degree - something that will become ever more common as the world wakes up to the potential of low-cost senolytic treatments that can remove senescent cells, one of the root causes of aging. As the article here makes clear, all it takes is a short period of changed calorie intake and weight to throw off most of the indirect metrics one might use to assess the results of an early, comparatively crude senolytic treatment. For individuals in the earlier stages of aging, benefits are likely to be subtle and more easily obscured. It is something to think about: consistency in lifestyle, particularly diet, is very important when trying to measure effects.
Gaining and losing weight causes extensive changes in the gut microbiota and in biomarkers related to inflammation and heart disease, researchers report. The researchers monitored subjects' omics profiles as they added extra snacks and beverages to their regular diets. "We were fortunate we got 23 people who would eat extra calories - typically 1,000 if you're male, 750 if you're female - every day for 30 days. They're just a very interested bunch of folks. They have to be to show this kind of dedication to giving samples." The team collected samples before and after the 30 days of eating extra calories, as well as after participants returned to their starting weight, about 60 days after dropping the extra calories, and then three months after that. Of the 23 participants, 13 were insulin resistant and 10 were insulin sensitive at the beginning of the study. Comparisons of baseline profiles showed differences in metabolism, transcript and protein levels, and the microbiota of insulin resistant and insulin sensitive people.
Although subjects only gained an average of about six pounds, the researchers detected considerable changes in molecules related to fat metabolism, inflammation, and dilated cardiomyopathy, a condition where the heart is less able to pump blood, which can lead to heart failure. The team also found differences in the gut microbiota after weight gain. Many of the shifts the scientists observed were less pronounced in the insulin-resistant individuals. For instance, one bacterial species - Akkermansia muciniphila, which is thought to help protect against the development of insulin resistance after weight gain - only appeared in the insulin-sensitive participants. "There is a molecular difference in the way [insulin] resistant and sensitive folks react to gaining weight, and we think it reflects differences in their underlying biochemistry."
Most of the changes went back to baseline after weight loss, but a few - such as molecules associated with folate metabolism - stayed elevated. And while the researchers saw some common responses to weight gain and loss across the group, "you still look more like you than somebody else. That means that our inherent biochemical profiles are pretty stable, at least through weight gain and weight loss."