Table 1 Organ-specific anti-aging effects of Hh signaling.
Organ | Year | Mechanism | Phenotype/function | References |
|---|---|---|---|---|
Brain | 2025 | Shh prevents proteasomal degradation of synaptic proteins | Preserved neuronal structure/function | |
2016 | Shh promotes hippocampal neurogenesis | Enhanced memory and neurogenesis in aged mice | ||
2015 | Dendrosomatic Shh signaling in hippocampal neurons | Maintains synaptic integrity under stress | ||
2017 | Shh enhances mitochondrial function | Neuronal survival in Parkinson’s models | ||
2018 | Shh maintains adult neural stem cell pools | Supports neural progenitor differentiation | ||
Liver | 2024 | Shh mitigates SASP in senescent hepatocytes | Restores liver homeostasis | |
2022 | Hh restoration in aged hepatic stellate cells | Improved regeneration, reduced fibrosis | ||
2023 | Regulated Shh activation | Supports survival and bile duct regeneration | ||
2021 | Shh hydrogel delivery | Restores function in irradiated liver | ||
2018 | Shh gene therapy | Reduced apoptosis and promoted regeneration | ||
Cardiac | 2022 | Shh-mediated angiogenesis and remodeling | Reduced fibrosis and enhanced regeneration | |
2018 | Shh promotes cardiac progenitor proliferation | Cardiac regeneration | ||
2006 | Shh-RAS anti-apoptotic survival signaling | Cardiomyocyte survival under stress | ||
Lung | 2025 | Hhip modulates Shh signaling | Alveolar epithelial repair | |
2019 | Shh maintains airway stem cell niches | Suppresses fibrotic remodeling | ||
2004 | Shh-Gli3 processing for morphogenesis | Supports alveolarization | ||
Bone/cartilage | 2022 | Hh supports osteocyte mechanotransduction | Maintains bone mass | |
2020 | Ihh represses senescence in bone marrow-derived MSCs | Promotes osteogenic potential | ||
2023 | Shh–Gli–Bmi1 axis in chondrocytes | Delays cartilage degeneration | ||
2019 | Shh promotes osteoblast differentiation | Bone formation | ||
2010 | Shh regulates matrix deposition | Supports osteogenesis | ||
Hair | 2022 | Shh reprograms follicular fibroblasts | Enhances HFSC proliferation | |
2009 | Shh maintains HFSC quiescence | Sustains cyclical regeneration | ||
Adipose | 2019 | Shh inhibits adipogenesis | Promotes osteogenic/chondrogenic lineage | |
2022 | Shh suppresses marrow adipogenesis | Supports bone and adipose balance | ||
Systemic | 2023 | Shh induces VEGF | Angiogenesis and endothelial regeneration | |
2023 | Shh enhances neural organoid patterning | Spinal cord regeneration | ||
2022 | Ihh anti-inflammatory signaling | Tissue homeostasis in kidney | ||
2021 | Shh enhances MSC survival | Stress resilience | ||
2018 | Shh gene therapy in fibrosis | Preserves erectile tissue |
