Disabled Macroautophagy

Definition

Disabled macroautophagy refers to impaired function of macroautophagy, the cellular recycling pathway that encloses damaged proteins, organelles, and cytoplasmic material in autophagosomes and delivers them to lysosomes for degradation. When this process is disabled or inefficient, cells become less able to clear damaged components and adapt to stress. [1] [2] [3]

Why It Matters in Ageing Research

Disabled macroautophagy is recognised as one of the expanded hallmarks of ageing because declining cellular recycling can contribute to loss of proteostasis, mitochondrial dysfunction, chronic inflammation, stem-cell exhaustion, and reduced tissue resilience. It is also relevant to longevity interventions because several nutrient-sensing and stress-response pathways influence autophagic activity. [4] [5] [6]

Common Confusion

• Disabled macroautophagy does not mean autophagy is completely absent; it can mean reduced, dysregulated, or insufficient autophagic flux.
• Macroautophagy is one form of autophagy; other forms include microautophagy and chaperone-mediated autophagy.
• Stimulating autophagy is not automatically beneficial in every context, because autophagy has tissue-specific and disease-specific effects.

Related Reading

• Hallmarks of Ageing
• Macroautophagy
• Autophagy
• Mitophagy
• Proteostasis
• mTOR

References

1. Mizushima, N., & Komatsu, M. (2011). Autophagy: Renovation of Cells and Tissues. https://doi.org/10.1016/j.cell.2011.10.026
2. Klionsky, D. J., & Emr, S. D. (2000). Autophagy as a Regulated Pathway of Cellular Degradation. https://doi.org/10.1126/science.290.5497.1717
3. Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008). Autophagy fights disease through cellular self-digestion. https://doi.org/10.1038/nature06639
4. Lopez-Otin, C., et al. (2023). Hallmarks of aging: An expanding universe. https://doi.org/10.1016/j.cell.2022.11.001
5. Rubinsztein, D. C., Marino, G., & Kroemer, G. (2011). Autophagy and Aging. https://doi.org/10.1016/j.cell.2011.07.030
6. Hansen, M., Rubinsztein, D. C., & Walker, D. W. (2018). Autophagy as a promoter of longevity: insights from model organisms. https://doi.org/10.1038/s41580-018-0033-y