Sympathetic nerve aging in mouse skin is sexually dimorphic and reversible
Male mice experience greater distal axon withdrawal that can be reversed by targeting muscle niches with nerve growth factor.
bioRxiv : the preprint server for biology · Pangilinan GR et al. · Paper published 7 Sep 2026
In a new preprint, researchers investigated sympathetic innervation in mouse skin across aging. They observed that sympathetic aging is sexually dimorphic, causing greater denervation in aged male mice compared to females. Sympathetic neuron cell bodies remained intact, revealing that peripheral denervation stems from distal axon withdrawal rather than cell death. This loss occurred alongside deterioration of the arrector pili muscle niche, which was more severe in males. However, aged sympathetic neurons remained responsive to nerve growth factor (NGF). Delivering NGF directly to arrector pili muscles restored sympathetic reinnervation and stimulated hair regeneration in aged males. Using genetic and endocrine models, the authors showed that these sex-divergent trajectories track with gonadal rather than chromosomal sex and are attenuated by early gonadectomy.
Why it matters
The findings show that age-related sympathetic decline is a reversible axonopathy influenced by local target tissues and gonadal factors, rather than irreversible neuronal death.
Caveats
The study was conducted exclusively in mice and is a preprint that has not yet undergone peer review.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Reversible, Sexually Dimorphic Sympathetic Aging: Distal Axon Withdrawal Shaped by Prepubertal Gonadal Influences
Pangilinan GR, Patil S, Mires F et al.
bioRxiv : the preprint server for biology · 7 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Core geroscience
- News value
- Important
- Evidence
- Animals
- Status
- Preprint
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