Unraveling Parkinson's Disease Neurodegeneration: Does Aging Hold the Clues?

Colin Coleman, Ian Martin

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations


Aging is the greatest risk factor for Parkinson's disease (PD), suggesting that mechanisms driving the aging process promote PD neurodegeneration. Several lines of evidence support a role for aging in PD. First, hallmarks of brain aging such as mitochondrial dysfunction and oxidative stress, loss of protein homeostasis, and neuroinflammation are centrally implicated in PD development. Second, mutations that cause monogenic PD are present from conception, yet typically only cause disease following a period of aging. Third, lifespan-extending genetic, dietary, or pharmacological interventions frequently attenuate PD-related neurodegeneration. These observations support a central role for aging in disease development and suggest that new discoveries in the biology of aging could be leveraged to elucidate novel mechanisms of PD pathophysiology. A recent rapid growth in our understanding of conserved molecular pathways that govern model organism lifespan and healthspan has highlighted a key role for metabolism and nutrient sensing pathways. Uncovering how metabolic pathways involving NAD+ consumption, insulin, and mTOR signaling link to the development of PD is underway and implicates metabolism in disease etiology. Here, we assess areas of convergence between nervous system aging and PD, evaluate the link between metabolism, aging, and PD and address the potential of metabolic interventions to slow or halt the onset of PD-related neurodegeneration drawing on evidence from cellular and animal models.

Original languageEnglish (US)
Pages (from-to)2321-2338
Number of pages18
JournalJournal of Parkinson's Disease
Issue number8
StatePublished - 2022


  • Aging
  • Parkinson's disease
  • metabolism
  • mitochondria

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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