The neural crest across the lifespan: Implications for aging, degeneration, and regeneration.

Abstract

The neural crest (NC) is a transient, multipotent cell population that contributes extensively to vertebrate embryogenesis, generating craniofacial structures, peripheral nerves, melanocytes, and cardiovascular elements. While classically studied in the context of development, increasing evidence demonstrates that NC-derived cells persist into adulthood, where they support tissue homeostasis, plasticity, and repair. This review synthesizes current insights into the lifelong impact of the NC, with emphasis on aging, degeneration, and regeneration. We first outline the developmental origins and lineage diversification of NC cells, highlighting mechanisms that establish long-lived progenitor pools. We then examine how age-related changes in NC-derived tissues, including craniofacial bone remodeling, pigmentary alterations, autonomic decline, and peripheral neuropathies, reflect broader principles of cellular senescence and disrupted signaling. The involvement of NC derivatives in age-associated pathologies, such as neurodegeneration, cardiac anomalies, and craniofacial degeneration, is also addressed. Finally, we highlight progress in regenerative medicine that leverages NC-derived stem and progenitor cells, together with molecular pathways that may rejuvenate their function in aging tissues. By integrating developmental, pathological, and regenerative perspectives, this review positions the NC as a central contributor to organismal aging and underscores its translational relevance. We also outline unresolved questions and future research directions at the interface of NC biology, aging, and regenerative medicine.