A moderate reduction in caloric intake can influence aging-related processes without the adverse effects seen with severe diets. While similar effects had previously been observed in mice, rhesus macaques, and fruit flies, a 40% reduction in diet in mice increased susceptibility to infections, impaired reproduction, and stunted growth. A new study published in Nature Aging links these potential benefits to the immune protein C3.
Yale University scientists examined plasma samples from 42 participants in the two-year CALERIE study, funded by the U.S. National Institutes of Health. The volunteers reduced their calorie intake by 11–14% without experiencing a significant sense of deprivation. Researchers had previously reported that a 14% calorie reduction over two years was associated with enhanced immune protection, with no impairment to growth or reproductive function.
The team analyzed over 7,000 proteins in plasma samples collected at various stages of the study. The most notable change following calorie restriction was a decrease in the level of complement component 3, or C3. The complement system plays a role in defending the body against pathogens; however, previous studies suggest that its activation may be linked to chronic inflammation and age-related diseases.
Comparing data from before and after the two-year diet revealed that white adipose tissue plays a key role in these changes. In experiments with mice, C3 expression increased with age, and visceral white adipose tissue was identified as a primary source of the protein. Further analysis showed that C3 is produced by aging-associated macrophages—immune cells residing within the adipose tissue. Over the course of two years of moderate calorie restriction, most participants lost about 18 pounds; however, no link was found between the reduction in body mass index and the decrease in complement protein levels. This suggests that the diet’s impact on adipose tissue extends beyond mere weight loss. The authors speculate that, in the future, some of the biological effects of calorie restriction might be replicated without the need for weight loss.
In experiments on mice, a drug that inhibits C3 activation reduced age-related inflammation. Researchers are now investigating the potential use of FDA-approved inhibitors to reduce C3 activity in humans. At the same time, the scientists emphasize that the complement system cannot be completely shut down, as the body requires it to fight infections.
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