Abstract
Dietary restriction (DR) extends lifespan in diverse organisms and, in animal and cellular models, can delay a range of aging-related
diseases including Alzheimer’s disease (AD). A better understanding of the mechanisms mediating these interactions, however, may reveal
novel pathways involved in AD pathogenesis, and potential targets for disease-modifying treatments and biomarkers for disease progression.
Drosophila models of AD have recently been developed and, due to their short lifespan and susceptibility to genetic manipulation, we have
used the fly to investigate the molecular connections among diet, aging and AD pathology. DR extended lifespan in both Arctic mutant A42
and WT 4R tau over-expressing flies, but the underlying molecular pathology was not altered and neuronal dysfunction was not prevented
by dietary manipulation.
Our data suggest that DR may alter aging through generalised mechanisms independent of the specific pathways
underlying AD pathogenesis in the fly, and hence that lifespan-extending manipulations may have varying effects on aging and functional
declines in aging-related diseases. Alternatively, our analysis of the specific effects of DR on neuronal toxicity downstream of Aand tau
pathologies with negative results may simply confirm that the neuro-protective effects of DR are upstream of the initiating events involved in
the pathogenesis of AD.
diseases including Alzheimer’s disease (AD). A better understanding of the mechanisms mediating these interactions, however, may reveal
novel pathways involved in AD pathogenesis, and potential targets for disease-modifying treatments and biomarkers for disease progression.
Drosophila models of AD have recently been developed and, due to their short lifespan and susceptibility to genetic manipulation, we have
used the fly to investigate the molecular connections among diet, aging and AD pathology. DR extended lifespan in both Arctic mutant A42
and WT 4R tau over-expressing flies, but the underlying molecular pathology was not altered and neuronal dysfunction was not prevented
by dietary manipulation.
Our data suggest that DR may alter aging through generalised mechanisms independent of the specific pathways
underlying AD pathogenesis in the fly, and hence that lifespan-extending manipulations may have varying effects on aging and functional
declines in aging-related diseases. Alternatively, our analysis of the specific effects of DR on neuronal toxicity downstream of Aand tau
pathologies with negative results may simply confirm that the neuro-protective effects of DR are upstream of the initiating events involved in
the pathogenesis of AD.
Original language | English |
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Pages (from-to) | 1977–1989 |
Number of pages | 13 |
Journal | Neurobiology of Aging |
Volume | 32 |
Issue number | 11 |
DOIs | |
Publication status | Published - 1 Nov 2011 |
Keywords
- Alzheimer’s disease
- aging
- Drosophila
- neuronal function