Is Parkinson's really a disease? Reframing it as a phenotype of aging.

The boundary between aging and neurodegenerative disorders remains unresolved, and emerging evidence challenges this dichotomy. Parkinson's disease (PD) has traditionally been defined as a neurodegenerative disease with motor and non-motor manifestations. It was not until two decades ago that clinical and research studies shed light on PD heterogeneity at the clinical, pathological, cellular, and genetic levels. In parallel, our understanding of aging mechanisms advanced, revealing shared mechanisms between aging and neurodegeneration, with numerous features overlapping with processes commonly associated with PD. These observations lead us to a fundamental question of whether we should consider PD and other neurodegenerative disorders as a distinct disease or if they are just a phenotypic manifestation of individuals during aging as a result of their genetic makeup and environmental factors over time. The heterogeneity of PD across clinical, pathological, cellular, pathogenic, and genetic levels mirrors the changes we observe during aging, seemingly driven by a shared mechanism. This viewpoint conceptualizes PD not as a distinct condition set apart from normality, but as a phenotype that evolves over time and is shaped by an individual's genetic makeup, much as each person ages along a unique trajectory. Considering PD from this angle may prompt a rethinking of how we classify neurodegenerative disorders, design clinical trials, and focus on patient-centered care. However, this viewpoint doesn't argue against PD as a clinically meaningful entity and doesn't overlook the suffering that our patients face during the course of the disease and the substantial burden experienced by them.