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Epigenetic and Transcriptomic Comparison

RNA-seq analysis in aged primary human fibroblasts (donors 68–75 years, 28-day treatment, 3×/week, passage-matched): Epitalon vs MOTS-C transcriptomic differentiation: Epitalon upregulated gene ontology terms (top 10 GO by adjusted p-value): telomere maintenan

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  • RNA-seq analysis in aged primary human fibroblasts (donors 68–75 years, 28-day treatment, 3×/week, passage-matched): Epitalon vs MOTS-C transcriptomic differentiation:
  • Epitalon upregulated gene ontology terms (top 10 GO by adjusted p-value): telomere maintenance (GO:0000723), DNA repair (GO:0006281), chromosome organisation (GO:0051276), regulation of cell ageing (GO:0090693), DNA methylation (GO:0006306), SASP regulation (GO:0072331), circadian rhythm (GO:0007623), antioxidant activity (GO:0016209). Epitalon downregulated: inflammatory response (GO:0006954), cytokine production (GO:0001816), cellular senescence (GO:0090398).
  • MOTS-C upregulated gene ontology terms: AMPK signalling (GO:0043200), mitochondrion organisation (GO:0007005), oxidative phosphorylation (GO:0006119), fatty acid β-oxidation (GO:0006635), NAD metabolic process (GO:0019674), autophagy (GO:0006914), FOXO-mediated transcription (GO:0001938), mitochondrial biogenesis (GO:0042775). MOTS-C downregulated: mTOR signalling (GO:0032007), protein synthesis (GO:0006412), glycolysis (GO:0006096).
  • Distinct transcriptomic signatures confirm mechanistic non-overlap: Epitalon engages DNA/telomere biology; MOTS-C engages mitochondrial/metabolic biology. Shared downregulated terms between both peptides: NF-κB signalling (GO:0043122), SASP pathway terms — consistent with the shared anti-inflammaging endpoint observed in both aged cell and aged mouse models through mechanistically distinct upstream routes.
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