Pink1 at the crossroads of aging, exercise, and diet in Parkinson’s disease: a mechanistic review

Pink1 (PTEN-induced kinase 1) is a key guardian of mitochondrial quality via mitophagy; its mutations are tightly linked to early-onset PD. This review synthesizes how aging, exercise, and high-fat diet (HFD) modulate Pink1 activity and thereby PD risk. Aging down-regulates Pink1 , impairing clearance of damaged mitochondria and promoting α -synuclein aggregation. Exercise up-regulates Pink1 -Parkin signaling, enhances PGC-1α and brain-derived neurotrophic factor (BDNF), and protects dopaminergic neurons in humans and rodents. Conversely, chronic HFD suppresses Pink1 , exacerbates oxidative stress, microglial activation and insulin resistance, accelerating Parkinson’s disease pathology. Cross-species cautions (mouse vs. primate) are highlighted. Targeting Pink1 -mediated mitophagy through lifestyle interventions offers a non-pharmacological strategy to delay PD onset and progression in aging populations.