Dietary restriction delays aging, but not neuronal dysfunction, in Drosophila models of Alzheimer's disease

Fiona Kerr, Hrvoje Augustin, M. D. W. Piper, Carina Gandy, Marcus J. Allen, Simon Lovestone, Linda Partridge

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)1977–1989
Number of pages13
JournalNeurobiology of Aging
Volume32
Issue number11
DOIs
Publication statusPublished - 1 Nov 2011

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Drosophila
Alzheimer Disease
Diptera
Molecular Pathology
Genetic Predisposition to Disease
Disease Progression
Animal Models
Biomarkers
Pathology
Diet

Keywords

  • Alzheimer’s disease
  • aging
  • Drosophila
  • neuronal function

Cite this

Kerr, Fiona ; Augustin, Hrvoje ; Piper, M. D. W. ; Gandy, Carina ; Allen, Marcus J. ; Lovestone, Simon ; Partridge, Linda. / Dietary restriction delays aging, but not neuronal dysfunction, in Drosophila models of Alzheimer's disease. In: Neurobiology of Aging. 2011 ; Vol. 32, No. 11. pp. 1977–1989.
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Dietary restriction delays aging, but not neuronal dysfunction, in Drosophila models of Alzheimer's disease. / Kerr, Fiona; Augustin, Hrvoje; Piper, M. D. W.; Gandy, Carina; Allen, Marcus J. ; Lovestone, Simon; Partridge, Linda.

In: Neurobiology of Aging, Vol. 32, No. 11, 01.11.2011, p. 1977–1989.

Research output: Contribution to journalArticle

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AU - Kerr, Fiona

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