The hallmarks of ageing are a widely used and evolving framework for understanding the molecular and cellular processes associated with age-related functional decline. Several of these processes are interconnected and are actively studied as potential contributors to age-related disease.
In NEC, inflammatory dysregulation, impaired regenerative responses and disrupted cellular stress pathways contribute to acute intestinal injury. These processes also overlap with areas of active research into age-related disease biology:
- Chronic inflammation
- Impaired cellular quality control (disabled macroautophagy)
- Reduced regenerative capacity (stem cell exhaustion).
Where these pathways damage a premature baby’s intestine in days, the same convergence degrades adult tissue over decades.
We selected NEC as the lead indication for Secretomix® because of the urgent unmet need. NEC gave us a defined regulatory pathway, an orphan indication, and clinical partners already in place, alongside biology that converges directly with the hallmarks of ageing.
Our neonatal pre-clinical models have characterised how we believe MRG1061 works and shown that it acts on these mechanisms, plus, in senescence models, on a fourth
- Cellular senescence
This compounds the same underlying failures over the longer adult timescale.
Chronic inflammation. NF-κB, a master switch of inflammatory gene activity is one of the most significantly enriched pathways when assessing the MRG1061 components, and its activity in stimulated human cell reporter lines was significantly reduced following administration of MRG1061.
In human immune cells, MRG1061 produced a consistent dose-dependent reduction in TNFα, reaching 59 per cent at the highest dose tested. Other pro-inflammatory cytokines, such as IL-6 also reduced while the anti-inflammatory mediators IL-10 and IL-1RA rose.
Stem cell exhaustion. Key intestinal stem cell niche markers were restored and proliferation increased in two separately established NEC models. Injured human lung epithelial cells also saw a stress response proliferative readout returned to uninjured levels.
Cellular senescence. Stress-induced senescence in human lung fibroblasts was reduced by more than half.
Impaired autophagy. Work at The Hospital for Sick Children (SickKids), Toronto, to which Micregen supplied material, showed that the extracellular vesicle fraction of a Secretomix® formulation restored autophagy-associated readouts towards control levels in both rat and human foetal lung models, through defined microRNAs in the miR17–92 cluster.
Beyond primary mechanism: disease-specific validation. Independent of these pathway findings, Secretomix® is also being tested directly in neurodegeneration models through an ongoing collaboration with the University of Bradford, one of the age-related disease areas where these mechanisms are expected to matter most.
The ageing hallmarks do not operate in isolation. Chronic inflammation can accelerate cellular senescence, while senescent cells can perpetuate inflammatory signalling. Together these processes compromise the stem cell niche and impair autophagy, creating a self-reinforcing network of dysfunction.
By acting across inflammation, senescence, stem cell niche integrity and autophagy, Secretomix® is designed to interrupt multiple points within this network. We therefore hypothesise that its direct effects on these four hallmarks may generate broader downstream benefits across the interconnected biological system.
The longevity applications of Secretomix® are held under a separate identity, Anageria™, and are available to a dedicated longevity partner. Micregen’s focus remains the NEC programme and first-in-human trials.
Progeria = Premature Ageing.
Anageria™ = Advancing the science of longevity.
Anageria™ represents the opposite direction from accelerated ageing: the pursuit of slower, healthier biological ageing.
The above data was generated in disease models rather than in dedicated ageing models. It is mechanistically compelling but it is not proof of an effect on ageing in humans. Formal validation in ageing models is a defined next step. Secretomix® and MRG1061 are investigational and not approved for clinical use.