E. Shyam P. Reddy, Professor and Director of the Cancer Biology Program, Department of Obstetrics and Gynecology at Morehouse School of Medicine, shared a post on LinkedIn:
“Calorie restriction lowers C3, an immune protein tied to aging and inflammation, improving health without requiring weight loss.
Cutting calories has long been linked to longer life – but there’s a catch. In animals, dialing back food intake can delay disease and extend lifespan, yet pushing it too far begins to backfire, weakening immunity and disrupting basic biology.
Now, scientists think they may be closing in on why. A study published in Nature Aging highlights an unexpected player, an immune protein called complement component 3 (C3), that could help explain how modest calorie reduction delivers benefits without the risks.
Earlier work from Yale found that people who reduced calorie intake by about 14% over two years showed stronger immune function without negative effects on growth or reproduction.
Aging as a Modifiable Process
‘This concept demonstrates that aging is actually malleable and a process that can be targeted,’
– says senior author Vishwa Deep Dixit, PhD, Waldemar Von Zedtwitz Professor of Pathology, professor of immunobiology and of comparative medicine, and director of the Yale Center for Research on Aging (Y-Age) at Yale School of Medicine.
Vishwa Deep Dixit
Vishwa Deep Dixit, DVM, PhD. Credit: Anthony DeCarlo
In the latest study, Dixit and colleagues analyzed plasma samples from 42 participants in a National Institutes of Health-funded two-year trial called the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy, or CALERIE.
‘It’s the only trial of its kind that has been done with such rigor and control and demonstrates relevance to human physiology.’
– Dixit says.
During the trial, participants were able to reduce their calorie intake by 11 to 14% without feeling deprived.
Discovery of C3 and Inflammation Link
The team identified more than 7,000 proteins in the samples. One protein, complement component 3 (C3), dropped significantly after calorie restriction. This protein drew attention because earlier research linked activation of the complement system, a group of proteins that help fight infections, to chronic inflammation, a key feature of aging and age-related diseases.
‘But the causal effects of C3 in aging and chronic inflammation have not been identified. So, we were very excited to find that in our study,’
– says Hee-Hoon Kim, PhD, a postdoctoral associate in the Dixit lab and a co-first author of the paper.
Comparing protein levels before and after two years of calorie restriction showed that white adipose tissue, the body’s main fat storage tissue, was the primary site affected.
Adipose Tissue and Aging Mechanisms
The researchers confirmed these results in animals. In mice, C3 levels increased with age, and further analysis indicated that visceral white adipose tissue drove this rise.
‘We were not expecting that because these proteins are mainly synthesized in the liver,’
– says Manish Mishra, PhD, a postdoctoral associate in the Dixit lab and a co-first author of the study.”
Title: Scientists Identify Immune Protein That Could Mimic Anti-Aging Effects of Calorie Restriction
Author: Kristel Tjandra
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