Vergara Nieto Álvaro Andrés, Diaz Andrés Halabi, Hernández Millaray, Sagredo Daniel
Departamento de Investigación y Desarrollo, Good Research and Science (GRS), Avenida Ramón Picarte 780, 5090000, Valdivia, Chile.
Facultad de Ciencias de La Salud, Escuela de Nutrición y Dietética, Universidad del Desarrollo, Ainavillo 456, 4070001, Concepción, Chile.
Curr Nutr Rep. 2025 Jun 6;14(1):78. doi: 10.1007/s13668-025-00666-9.
This research aims to elucidate the molecular mechanisms by which intermittent fasting (IF) induces autophagy and to evaluate its therapeutic potential across a range of pathologies. By synthesizing findings from preclinical and clinical studies, the review seeks to clarify the roles of key signaling pathways-such as the AMPK-mTOR axis, sirtuins, and β-hydroxybutyrate-mediated signaling-in orchestrating autophagic processes, thereby enhancing cellular resilience and metabolic homeostasis.
Recent evidence demonstrates that IF robustly activates autophagy in metabolically active tissues through conserved molecular pathways. Experimental studies reveal that fasting increases AMPK phosphorylation and inhibits mTOR activity, leading to enhanced expression of autophagy markers like LC3-II, Beclin-1, and ATG proteins. Additionally, IF has been shown to improve insulin sensitivity, reduce hepatic lipid accumulation, and mitigate neurodegenerative processes by promoting the clearance of toxic protein aggregates. Emerging clinical data further support these findings, indicating that tailored fasting protocols can modulate autophagy to yield benefits in metabolic, oncological, and neurodegenerative disorders. The scoped literature underscores IF as a promising non-pharmacological strategy to induce autophagy and improve overall health. While robust preclinical and clinical evidence supports its beneficial effects, challenges remain in standardizing fasting protocols and identifying optimal biomarkers for monitoring autophagic activity. Future research should focus on long-term, well-controlled trials and combined therapeutic approaches to refine IF strategies, ultimately translating these insights into personalized dietary interventions for disease prevention and health optimization.
本研究旨在阐明间歇性禁食（IF）诱导自噬的分子机制，并评估其在一系列病理状况下的治疗潜力。通过综合临床前和临床研究的结果，本综述旨在阐明关键信号通路（如AMPK - mTOR轴、sirtuins和β - 羟基丁酸介导的信号通路）在协调自噬过程中的作用，从而增强细胞弹性和代谢稳态。
最近的证据表明，IF通过保守的分子途径在代谢活跃组织中强烈激活自噬。实验研究表明，禁食会增加AMPK磷酸化并抑制mTOR活性，导致自噬标志物（如LC3 - II、Beclin - 1和ATG蛋白）的表达增强。此外，IF已被证明可以改善胰岛素敏感性、减少肝脏脂质积累，并通过促进有毒蛋白质聚集体的清除来减轻神经退行性过程。新出现的临床数据进一步支持了这些发现，表明定制的禁食方案可以调节自噬，从而在代谢、肿瘤和神经退行性疾病中产生益处。有针对性的文献强调IF是一种有前景的诱导自噬和改善整体健康的非药物策略。虽然有力的临床前和临床证据支持其有益效果，但在标准化禁食方案和确定监测自噬活性的最佳生物标志物方面仍存在挑战。未来的研究应专注于长期、严格控制的试验以及联合治疗方法，以完善IF策略，最终将这些见解转化为用于疾病预防和健康优化的个性化饮食干预措施。
