Research
Hormonal
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.
In aging, fat tissue (specifically visceral fat) becomes a source of inflammation due to immune cells (macrophages) producing complement proteins like C3a. This process is driven by specific signaling pathways within these cells.
GoodSupportsHIGH confidence
adipose tissue macrophages (ATMs) were identified as the primary cellular source of age-associated C3 production, and downstream signaling through the extracellular signal-regulated kinase (ERK) pathway mediated the production of inflammatory cytokines in an autocrine manner.
Why this rating
Strong mechanistic evidence from mouse models using scRNA-seq, flow cytometry, and ex vivo experiments.
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
preprint · n=42Cited 1×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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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
- Pharmacological inhibition of Complement C3 using AMY-101 improves healthspan, metabolic fitness, and reduces inflammaging in aged mice.Good
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