Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster.
BACKGROUND
We characterized RNA transcript levels for the whole Drosophila genome during normal aging. We compared age-dependent profiles from animals aged under full-nutrient conditions with profiles obtained from animals maintained on a low-calorie medium to determine if caloric restriction slows the aging process. Specific biological functions impacted by caloric restriction were identified using the Gene Ontology annotation. We used the global patterns of expression profiles to test if particular genomic regions contribute differentially to changes in transcript profiles with age and if global disregulation of gene expression occurs during aging.


RESULTS
Whole-genome transcript profiles contained a statistically powerful genetic signature of normal aging. Nearly 23% of the genome changed in transcript representation with age. Caloric restriction was accompanied by a slowing of the progression of normal, age-related changes in transcript levels. Many genes, including those associated with stress response and oogenesis, showed age-dependent transcript representation. Caloric restriction resulted in the downregulation of genes primarily involved in cell growth, metabolism, and reproduction. We found no evidence that age-dependent changes in transcription level were confined to genes localized to specific regions of the genome and found no support for widespread disregulation of gene expression with age.


CONCLUSIONS
Aging is characterized by highly dynamic changes in the expression of many genes, which provides a powerful molecular description of the normal aging process. Caloric restriction extends life span by slowing down the rate of normal aging. Transcription levels of genes from a wide variety of biological functions and processes are impacted by age and dietary conditions.
Pletcher
Scott D
SD
Department of Biology, University College London, The Darwin Building, Gower Street, London WC1E 6BT, UK. s.pletcher@ucl.ac.uk
Macdonald
Stuart J
SJ
Marguerie
Richard
R
Certa
Ulrich
U
Stearns
Stephen C
SC
Goldstein
David B
DB
Partridge
Linda
L
D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D002149:Energy Intake / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D014158:Transcription, Genetic
D029721:Drosophila Proteins