Review: intracellular complement (complosome) in senescence and age-related disease
This review describes how intracellular C3, and in some contexts intracellular C5, interact with mTOR, NF-κB and AMPK pathways and with hallmarks of aging, and discusses organ-specific effects and possible therapeutic strategies. [1]
Automatic summary · not editorially reviewed
The key findings
The review describes crosstalk of intracellular C3, and intracellular C5 in certain contexts, with the mTOR, NF-κB and AMPK pathways. [1]
The review details how intC3 intersects with canonical hallmarks of aging, including cellular senescence and mitochondrial dysfunction. [1]
The review discusses therapeutic strategies and names gaps in compartment-specific tools, conditional knockouts and longitudinal models. [1]
The source at a glance
- Study type / format
- Review (abstract only)
- Population / context
- Cells and organ systems discussed in aging research, as summarized in a review
- Summary based on
- Study abstract
- Original publication
- July 29, 2026
Complosome review links intC3 to aging hallmarks
The review treats the complement system not only as a systemic extracellular defense but also as an intracellular network, the complosome. It summarizes research on how intracellular C3 (intC3), and intracellular C5 (intC5) in certain contexts, crosstalk with the mTOR, NF-κB and AMPK pathways. It details how intC3 intersects with several canonical hallmarks of aging, including cellular senescence, mitochondrial dysfunction, loss of proteostasis, genomic instability, epigenetic alterations, altered intercellular communication, stem cell exhaustion and deregulated nutrient sensing.
Supporting source [1]
Organ-specific intC3 effects and proposed strategies
The review examines organ-specific consequences of intC3 dysregulation in the aging brain, liver, eye, kidney, vasculature, lung and immune system, as well as in cancer. It discusses therapeutic strategies including complement inhibitors, senolytics, senomorphics, RNA interference, proteolysis targeting chimeras (PROTACs) and nanotechnology-enabled delivery. These are discussed strategies, not established treatments.
Supporting source [1]
Gaps named: compartment tools and longitudinal models
The review outlines critical gaps in compartment-specific tools, conditional knockouts and longitudinal models. It states that precision strategies preserving systemic complement function while selectively modulating intracellular pools will be essential to translate complosome biology into durable interventions for age-related diseases. This is a proposed research direction, not a validated intervention.
Supporting source [1]
How to interpret this
This is an abstract of a review; the full text was not reviewed. The abstract summarizes other research and proposes strategies and research directions rather than reporting new primary data or validated treatments.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Gold NM, Okeke MN, Ajoronor SE, He Y. · europepmc.org · July 29, 2026