Progressive age is the single major risk factor for neurodegenerative diseases. Cellular aging markers during the course of Parkinson’s disease (PD) have been implicated in previous studies, however majority of these studies have investigated the association of individual cellular aging hallmarks with PD but not jointly.
Here, we have studied the association of PD with three aging hallmarks (telomere attrition, mitochondrial dysfunction, and cellular senescence) in blood and the brain tissue. Telomere length and mitochondrial DNA ( mtDNA ) copy number was assessed by qPCR, while mitochondrial function ( PGC-1α and PGC-1β ) and expression of cyclin-dependent kinase inhibitor 2A ( CDKN2A ), cellular senescence marker was measured by RT-qPCR.
Our results show that patients diagnosed with PD had 20% lower mitochondrial DNA copy number but 26% longer telomeres in blood compared to controls. Moreover, telomere length in blood was positively correlated with medication (Levodopa Equivalent Daily Dose). Similar results were found in brain tissue, where patients with Parkinson’s disease (PD), Parkinson dementia (PDD) and Dementia with Lewy Bodies (DLB) showed (46-95%) depleted mtDNA copy number, but (7-9%) longer telomeres compared to controls. Furthermore, when compared to controls, patients had lower mitochondrial biogenesis ( PGC-1α and PGC-1β ) and higher load of cellular senescent cells in postmortem prefrontal cortex tissue, where DLB showing the highest effect among the patient groups.
Our results show that mitochondrial dysfunction and cellular senescence but not telomere shortening is associated with PD, PDD and DLB. Our findings suggest that mitochondrial copy number and function could be used as viable biomarker in blood as an early indicator for the risk of neurodegenerative diseases.