Hormonal
Pharmacological inhibition of Complement C3 using AMY-101 improves healthspan, metabolic fitness, and reduces inflammaging in aged mice.
In aged mice, weekly injections of a C3 inhibitor (AMY-101) improved metabolic health and physical function. This suggests that targeting the complement system could be a viable strategy to combat age-related decline, potentially mimicking the benefits of caloric restriction.
Specific small molecule-mediated systemic C3 inhibition reduced inflammaging, improved metabolic homeostasis, and enhanced healthspan of aged mice.
Why this rating
Strong evidence from aged mouse models with clear healthspan metrics, though human data is limited to observational proteomics.
Source
Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging
Manish Mishra et al. · Nature Aging · 2025
DOI 10.1038/s43587-026-01107-0
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- Caloric restriction (14% reduction for 2 years) reduces circulating C3a levels in humans, independent of BMI changes, thereby suppressing complement-mediated inflammation.Good
- Age-associated elevation of C3a in visceral adipose tissue (VAT) is primarily driven by adipose tissue macrophages (ATMs) via an autocrine ERK-dependent signaling loop.Good
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