SuperAging vs. Alzheimer’s Disease – The Two Extremes of Healthy and Unhealthy Aging
Project Outline
The phenomenon of individuals performing above the average even in old age suggests that these individuals must obtain resistance mechanisms that allow them to become so-called super agers. Indeed, recent studies reported that the structural and functional integrity of these super-agers remains resistant to aging processes. Thus, these individuals may be able to maintain their brain energy homeostasis despite advanced age and may be able to resist the build-up of neurotoxic proteins.
The opposite extreme of super-aging are individuals with Alzheimer’s disease. These individuals show an acceleration in aging-related changes of the brain and are not able to maintain their brain energy homeostasis. Nonetheless, some patients with Alzheimer’s disease can better cope with the effects of the disease than others. This observation points towards resilience factors that allow for the compensation of aging- and disease- associated processes that are likely fostered by lifestyle factors.
Given these two extremes of aging, gene x environment interactions in form of epigenetic alterations and protective lifestyle factors have recently been considered in the heterogeneous process of unhealthy and successful brain aging. In particular, the role of microRNAs has been suggested to play a pivotal role in in the regulation of genes and aging-related pathophysiological processes. Although several epigenetic mechanisms have already been determined by histopathological studies of Alzheimer’s disease patients and some data is available of miRNA signatures in super-agers, it remains elusive how epigenetic modifications and lifestyle factors are related to the pathophysiological processes and functional and structural network function associated with successful healthy aging (i.e. super-aging) and unhealthy aging (i.e. Alzheimer’s disease).
Using a multimodal imaging approach the aim of this project is to elucidate resilience (i.e. coping mechanisms in the phase of pathology) and resistance (i.e. avoidance mechanisms against the build-up of pathology) factors on the structural, functional and metabolic level and to set these mechanisms in association with epigenetic modifications in a group of super-agers, normal agers and patients with early Alzheimer’s disease.
Methodology & Research Model
Multimodal neuroimaging (structural and functional MRI, PET) in super-agers (individuals with superior memory performance at age of 80 years), normal-agers and patients with mild cognitive impairment.
Epigenetic screening of differences in microRNA levels.
Requirements for Application
Basic knowledge in processing of neuroimaging data (e.g. functional and structural MRI) and statistics.
Publications
For all relevant publications, please visit the website:
www.mmni.de