title: Ageing and Parkinson's disease: why is advancing age the biggest risk factor?
abstract: As the second most common age related neurodegenerative disease after Alzheimer's disease, the health, social and economic impact resulting from Parkinson's disease will continue to increase alongside the longevity of the population. Ageing remains the biggest risk factor for developing idiopathic Parkinson's disease. Although research into the mechanisms leading to cell death in Parkinson's disease has shed light on many aspects of the pathogenesis of this disorder, we still cannot answer the fundamental question, what specific age related factors predispose some individuals to develop this common neurodegenerative disease. In this review we focus specifically on the neuronal population associated with the motor symptoms of Parkinson's disease, the dopaminergic neurons of the substantia nigra, and try to understand how ageing puts these neurons at risk to the extent that a slight change in protein metabolism or mitochondrial function can push the cells over the edge leading to catastrophic cell death and many of the symptoms seen in Parkinson's disease. We review the evidence that ageing is important for the development of Parkinson's disease and how age related decline leads to the loss of neurons within this disease, before describing exactly how advancing age may lead to substantia nigra neuronal loss and Parkinson's disease in some individuals.
authors: Newcastle University Centre for Brain Ageing and Vitality, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address: amy.reeve@newcastle.ac.uk.
authors: Amy
authors: A
authors: Reeve
authors: Newcastle University Centre for Brain Ageing and Vitality, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address: e.m.simcox@newcastle.ac.uk.
authors: Eve
authors: E
authors: Simcox
authors: Newcastle University Centre for Brain Ageing and Vitality, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK. Electronic address: doug.turnbull@newcastle.ac.uk.
authors: Doug
authors: D
authors: Turnbull
mesh_terms: D000375:Aging / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D028361:Mitochondrial Diseases / Q000150:complications; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology*; D011489:Protein Denaturation; D013378:Substantia Nigra / Q000502:physiology*
keywords: Ageing; Mitochondria; Neurodegeneration; Parkinson's disease