Autophagy is the name given to an important collection of processes that identify broken and unwanted cellular structures and convey them to a lysosome, where they are broken down and recycled. The identification and conveyance differ greatly from target to target, but all of the specific forms of autophagy converge on delivery to a lysosome. Up to a point, more autophagy and more efficient autophagy improves cell function by clearing out damaged and dysfunctional structures and protein machinery. This in turn translates to a modest slowing of aging if sustained over time throughout the body, which is why the research community spends so much time focused on autophagy. Here, researchers discuss mitophagy, meaning autophagy of mitochondria, and its importance in maintaining cell function.
Mitochondrial dysfunction is one of the core drivers of aging. It is manifested by reactive oxygen species (ROS) accumulation, mitochondrial DNA (mtDNA) mutations, imbalanced energy metabolism, and abnormal biosynthesis. Mitochondrial autophagy maintains cellular homeostasis by selectively removing damaged mitochondria through mechanisms including the ubiquitin-dependent pathway (PINK1/Parkin pathway) and the ubiquitin-independent pathway (mediated by receptors such as BNIP3/FUNDC1).
During aging, the decrease in mitochondrial autophagy efficiency leads to the accumulation of damaged mitochondria, forming a cycle of mitochondrial damage-ROS-aging damage and aggravating aging-related diseases such as neurodegenerative diseases and cardiovascular pathologies. The targeted regulation of mitochondrial autophagy (drug modulation and exercise intervention) can restore mitochondrial function and slow aging. However, autophagy has a double-edged sword effect; moderate activation is anti-aging, but excessive activation or dysfunction accelerates the pathological process. Therefore, targeting mitochondrial autophagy may be an effective anti-aging technique; however, future focus should be on the tissue-specific regulatory threshold and the dynamic balance mechanism to achieve precise intervention.
Link: https://doi.org/10.1038/s41420-025-02913-y
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