Systems Biology of Aging: Opportunities for Parkinson’s Disease

Abstract

Parkinson's disease (PD), like many other dementias, is a disease of old age with neurological-pathological signs and underlying molecular mechanisms that precede cell death. Deciphering PD specifically from an aging perspective has many advantages. PD shares multiple mechanisms with aging, albeit in an accelerated fashion, including accumulation of damage and dysfunction, stress responses, and deficiencies in the maintenance of protein quality. Here, we review the foundations of a new hybrid, phenotypical model, which combines organelle phenotypes with molecular mechanisms associated with the long-term progression of normal aging. Subsequently, we adapt this model to PD and demonstrate the acceleration of dysfunction. On the level of molecular mechanisms, we specifically discuss two pathways that play a key role in the progression of both aging and PD: NF-kB and mTOR. The introduction of comprehensive modeling approaches is expected to make a significant contribution in deciphering the relationship between the different processes and risks factors. In particular, the tight relationship of aging and PD as discussed here sheds new light on future strategies for interventions.