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Published on: March 23, 2011
Skin-innervating glutamatergic neurons modulate aging
Zhikai Wang1, Xinping Jin1, Yue Wu1
1Precision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.
Peripheral nerves slow skin aging by releasing glutamate. Loss of neurofilament heavy chain (Nefh) in these nerves accelerates aging, collagen loss, and fibroblast senescence, highlighting a new therapeutic target for skin disorders.
Area of Science:
- Neuroscience
- Dermatology
- Molecular Biology
Background:
- Peripheral nerves influence skin homeostasis via neurotransmitters.
- The specific role of nerves in skin aging is not fully understood.
- Collagen reduction is a hallmark of aged skin.
Purpose of the Study:
- To investigate the role of peripheral nerves, specifically glutamatergic neurons, in skin aging.
- To elucidate the molecular mechanisms underlying nerve-mediated regulation of skin aging and collagen production.
Main Methods:
- Studied aged skin for changes in neurofilament heavy chain (Nefh) expression.
- Utilized genetic deletion of Nefh in specific neuronal populations (Vglut2+) in mice.
- Assessed skin aging phenotypes, including collagen levels and fibroblast senescence.
- Investigated molecular interactions involving Nefh, Vglut2, Cdk5, and Slc1a3.
Main Results:
- Cutaneous denervation accelerated skin aging and collagen reduction.
- Nefh expression decreased in aged skin and was localized to Vglut2+ neurons.
- Nefh deletion in Vglut2+ neurons induced fibroblast senescence and collagen loss.
- Glutamate supplementation ameliorated skin aging phenotypes.
- Cdk5 interacts with Nefh and Vglut2 to maintain glutamate release and collagen homeostasis.
- Slc1a3 in fibroblasts mediates glutamate's anti-aging effects.
Conclusions:
- Nefh-mediated glutamatergic neuromodulation is crucial for maintaining skin aging and collagen homeostasis.
- Targeting the Nefh-glutamate pathway offers potential therapeutic strategies for aging-related skin disorders.
