ReviewRedox proteomics and the dynamic molecular landscape of the aging brain
Section snippets
The dynamic of brain aging
The definition of aging comprises the collection of changes that make human beings progressively more likely to die (Singh and Newman, 2011). Indeed, one hallmark of aging in humans is an age-related increase in mortality. “Normal” brain aging and its association with age-associated brain disorders is an understudied area of research, likely due to the general awareness that aging is an inescapable process which most often overlaps with age-associated diseases, and therefore is not easily
Oxidative stress, mitochondria and brain aging
Aging is a natural process that defines all living organisms. While cell division and oxidative phosphorylation are a requirement that sustains most life on this planet, these processes become deleterious over time. It has been proposed that free radicals generated by oxidative phosphorylation within the mitochondria play a central role in the normal aging process and in conjunction with the decrease in antioxidant defence systems observed (Perrig et al., 1997, Perkins et al., 1999, Rinaldi et
Redox proteomics strategies
General methods of detecting protein oxidation in homogenates are useful for getting a sense as to the redox state of the cell, however they do not provide an accurate detailed account of specific protein oxidation occurring in a system. Redox proteomics is a set of techniques which allow for the identification of specific target proteins that may be differentially oxidized as a result of oxidative injury. There are two prominent methods that allow for the use of redox proteomics, those being
SAMP8 mice
The senescence-accelerated mouse (SAM) is the result of a phenotypic selection from a common genetic pool of AKR/J strain of mice, which were noticed to become senile at an early age and had a shorter life span (Takeda et al., 1981). Among certain littermates of AKR/J mice, five of these litters with early senescence were selected as the progenitors of the senescence-accelerated-prone mice (SAMP). Interestingly, SAMP8 mice showed characteristic learning and memory deficits at old age (Flood and
Aging and neurodegeneration: focus on Alzheimer's disease
The most comprehensive proteomics study of human aging, or, more correctly, dysfunctional human brain in a disorder associated with aging, has been performed by our group on AD post-mortem human brain. AD is the most common form of dementia in the elderly population, clinically characterized by progressive memory loss, cognitive impairment, loss of language and motor skills, and changes in behavior not due to any other cause. AD brain, CSF, and plasma demonstrate increased levels of OS (Di
Concluding remarks
Aging is an accumulative process in that damage over time builds up to a critical mass promoting system failure that results in mortality as well as age related diseases. CNS is particularly vulnerable to oxidative injury, and accumulation of oxidative damage in the brain results from either perturbation of redox balance and reduced ability of antioxidant/clearance systems to correctly metabolize oxidized/misfolded proteins. Alteration of intracellular redox homeostasis may in turn stimulate
Acknowledgement
This work was in part supported by a NIH grant to D.A.B. [AG-05119].
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