The GHK-Cu delays aging in Caenorhabditis elegans via coordinated regulation of mitochondrial function and activation of DAF-16/SKN-1 pathways
Wen H, Zhao K, Luo X, Pu J, Li Y, Dou Y
Biogerontology (2026)
The first mechanistic model-organism study to show GHK-Cu extends Caenorhabditis elegans lifespan via DAF-16 and SKN-1 activation coupled with restoration of mitochondrial fusion dynamics — a translational bridge between GHK-Cu's well-documented dermatological signal and the broader geroprotective hypothesis.
This is the first published mechanistic study to test GHK-Cu's geroprotective claim in a tractable invertebrate longevity model. Wen, Zhao and colleagues at Yunnan University and Kunming Medical University used Caenorhabditis elegans — the canonical aging-research model whose insulin/IGF-1-signalling (DAF-16/FOXO) and Nrf2-orthologue (SKN-1) pathways are extensively characterised — to ask whether GHK-Cu treatment extends lifespan and through what pathway.
GHK-Cu significantly extended C. elegans lifespan (magnitude not stated in the abstract) and improved a battery of healthspan markers: resistance to oxidative and thermal stress, motility, pharyngeal pumping rate, defecation rhythm, and reduced lipofuscin / lipid accumulation. Mechanistically, GHK-Cu raised mitochondrial membrane potential, reduced age-associated mitochondrial network fragmentation, shifted mitochondrial dynamics toward fusion by modulating drp-1 (fission) and fzo-1 (fusion) expression, and increased ATP biosynthesis.
The DAF-16 and SKN-1 stress-response pathways were activated, with upregulation of downstream antioxidant and antimicrobial effectors sod-3 (superoxide dismutase), gst-4 (glutathione S-transferase), gcs-1 (γ-glutamylcysteine synthetase), lys-7 and lys-8.
The published abstract does not state the GHK-Cu dose, treatment regimen, or the absolute magnitude of lifespan extension — these are the load-bearing quantitative results and must be verified against the full paper before downstream citation. Full-text access is paywalled at Springer; this entry flags these gaps explicitly.
C. elegans is a powerful but imperfect translation model for mammalian aging: the canonical pathways (insulin/IGF-1, mTOR, sirtuin, antioxidant response) are well-conserved, but the absolute magnitude of any C. elegans lifespan effect typically does not transfer linearly to mammalian healthspan.
The DAF-16 and SKN-1 dependence claim is suggestive but the abstract does not state whether the lifespan extension is abolished in daf-16 or skn-1 mutant strains — the standard mechanistic test. This work is single-laboratory and unreplicated. Despite these gaps it is the first GHK-Cu C. elegans lifespan paper, and the pathway architecture (mitochondrial fusion + FOXO/Nrf2 activation) is mechanistically plausible and consistent with Pickart's longstanding gene-modulation framing.
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