Role of C3 protein in slowing down aging has been revealed

The study was based on an analysis of plasma samples from 42 participants in the two-year CALERIE clinical trial, during which volunteers reduced their calorie intake by 11-14%. The researchers examined more than 7,000 proteins and found that the C3 component showed the most significant decrease. Previously, the activation of the complement system has been associated with the development of chronic systemic inflammation, which is a fundamental feature of biological aging and a driver of age-related diseases.

Using single-cell RNA sequencing, scientists have determined that the main source of excess C3 protein during aging is not the liver, as previously believed, but visceral white adipose tissue. The specific producers of this protein were found to be specific age-related macrophages located within the adipose depots. This discovery challenges the traditional view of adipose tissue as a passive energy storage, elevating it to the status of an active regulator of immune aging.

An important finding of the study was the absence of a direct correlation between the decrease in C3 protein levels and overall body weight loss. Although the participants lost an average of about 8 kilograms over two years, an analysis of the body mass index showed that the beneficial effect of calorie restriction was due to specific changes in adipose tissue, rather than simply weight loss. This opens up the possibility of achieving an anti-aging effect without the need for strict diets, through direct pharmacological intervention on the C3 protein.

The results of this study support the theory of antagonistic pleiotropy, which suggests that mechanisms that protected individuals from infections in their early years (such as the complement system) may become detrimental as they age. In mouse experiments, the use of C3 inhibitors reduced age-related inflammation, mimicking the effect of calorie restriction. Currently, researchers are exploring the potential of approved drugs to restore balance in the complement system, which could be a key to extending human healthspan.