Parkinson’s Disease and Aging

Abstract

Parkinson’s disease (PD) is a slowly progressive neurodegenerative syndrome, the most prevalent movement disorder amongst the elderly population. The average onset of disease is 60 years of age. It is historically associated chiefly with motor deficits, although recently it has been shown to include significant non-motor effects. Cardinal motor symptoms result from preferential loss of a subset of dopaminergic neurons within the substantia nigra pars compacta. Molecular changes associated with this neuronal cell loss include mitochondrial dysfunction, reduction in protein homeostasis, increase in oxidative and inflammatory damage, and mishandling of cellular calcium. Although therapies exist that improve symptoms, there is currently no prevention or cure for the disease. Several hallmarks of the disease coincide with events that are also linked to aging, suggesting that aging is not merely a risk factor, but an underlying cause of the disease in susceptible individuals who, based on genetic and environmental factors ultimately present with PD. Understanding the relationship between processes that drive aging and their potential impact on age-related neurodegenerative disease could therefore provide powerful new avenues of therapy. Here we review the potential role of several such changes including age-related losses in ability to cope with stress (‘resilience’), systemic inflammaging, brain cellular senescence affecting function of both endogenous and transplanted neurons, and the role of age-related epigenetic alterations on cellular dopaminergic dynamics. The need for expanded research towards a better understanding of the interrelationship between genes and environment (the ‘exposome’) in aging and PD is also discussed.