Mitochondrial dysfunction
Energy-producing mitochondria become less efficient, increasing oxidative stress and cellular damage.
Declining oxidative phosphorylation efficiency increases ROS leak, reduces ATP output, and can activate inflammasomes. Mitochondrial DNA mutations clonally expand with age; failed mitophagy allows defective mitochondria to persist in post-mitotic cells.
How to minimize mitochondrial dysfunction
- Zone 2 aerobic training increases mitochondrial biogenesis (PGC-1α) and oxidative capacity—strong human evidence.
- Resistance training preserves muscle mitochondrial content and supports NAD+ salvage pathways.
- Cold exposure and hypoxic conditioning may induce mitophagy; human longevity data remain limited.
- Urolithin A, CoQ10, and NAD+ precursors show mixed biomarker results—none proven to extend human lifespan.