Scientists have identified a protein, complement component three (C3), that may offer a way to achieve some anti-aging benefits of calorie restriction without severe dieting. Moderate calorie restriction lowered C3 levels in human participants. Blocking C3 reduced age-related inflammation in mice. This suggests future treatments could mimic calorie restriction's benefits.
Calorie restriction has extended the lifespan of animals like mice, rhesus monkeys, and fruit flies. These animals often remained healthier for longer. However, severe calorie restriction can lead to negative effects. These include increased vulnerability to infections, reduced reproduction, and impaired growth.
Researchers at Yale School of Medicine previously showed that moderate calorie restriction improved immune defenses in humans. Participants cut calorie intake by 14% for two years. They did not experience growth or reproduction issues. The new study examined plasma samples from 42 participants in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) trial. This trial involved an 11% to 14% calorie reduction.
The team analyzed over 7,000 proteins in these samples. C3 levels significantly decreased after calorie restriction. C3 is an immune protein. Earlier research linked the complement system, which includes C3, to chronic inflammation. This inflammation is a key factor in aging and age-related diseases.
White adipose tissue, or fat tissue, appeared to be the primary tissue affected by the dietary change. C3 expression increased with age in mice. Visceral white adipose tissue was a major source of this age-related C3 increase. Single-cell RNA sequencing pinpointed age-associated macrophages within adipose tissue as the source of C3 production.
Reducing C3 levels could offer benefits independent of weight loss. Participants in the study lost about 18 pounds. However, no relationship was found between the amount of weight lost and the decline in complement protein levels. Inhibiting C3 activation in mice reduced age-related inflammation. Researchers are now investigating if existing FDA-approved drugs can suppress C3 production to slow aspects of aging in humans.
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