Biomarkers of aging in Drosophila.
Low environmental temperature and dietary restriction (DR) extend lifespan in diverse organisms. In the fruit fly Drosophila, switching flies between temperatures alters the rate at which mortality subsequently increases with age but does not reverse mortality rate. In contrast, DR acts acutely to lower mortality risk; flies switched between control feeding and DR show a rapid reversal of mortality rate. Dietary restriction thus does not slow accumulation of aging-related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of aging-related damage. However, molecular species that switch upon instigation or withdrawal of DR are thus potential biomarkers of mechanisms underlying risk of mortality, but not of aging-related damage. Using this approach, we assessed several commonly used biomarkers of aging-related damage. Accumulation of fluorescent advanced glycation end products (AGEs) correlated strongly with mortality rate of flies at different temperatures but was independent of diet. Hence, fluorescent AGEs are biomarkers of aging-related damage in flies. In contrast, five oxidized and glycated protein adducts accumulated with age, but were reversible with both temperature and diet, and are therefore not markers either of acute risk of dying or of aging-related damage. Our approach provides a powerful method for identification of biomarkers of aging.
Jacobson
Jake
J
Institute for Healthy Ageing, Department of Genes, Evolution and Environment, University College London, London WC1E 6BT, UK; Max Planck Institute for Biology of Ageing, Gleueler Strasse. 50 a, D-50931, Cologne, Germany.
Lambert
Adrian J
AJ
MRC Mitochondrial Biology Unit, Hills Rd, Cambridge CB2 2XY, UK.
Portero-Otín
Manuel
M
Metabolic Pathophysiology Research Group, Department of Experimental Medicine, University of Lleida-IRBLLEIDA, Lleida 25008, Spain.
Pamplona
Reinald
R
Metabolic Pathophysiology Research Group, Department of Experimental Medicine, University of Lleida-IRBLLEIDA, Lleida 25008, Spain.
Magwere
Tapiwanashe
T
Institute for Healthy Ageing, Department of Genes, Evolution and Environment, University College London, London WC1E 6BT, UK; Max Planck Institute for Biology of Ageing, Gleueler Strasse. 50 a, D-50931, Cologne, Germany.
Miwa
Satomi
S
MRC Mitochondrial Biology Unit, Hills Rd, Cambridge CB2 2XY, UK.
Driege
Yasmine
Y
Institute for Healthy Ageing, Department of Genes, Evolution and Environment, University College London, London WC1E 6BT, UK; Max Planck Institute for Biology of Ageing, Gleueler Strasse. 50 a, D-50931, Cologne, Germany.
Brand
Martin D
MD
MRC Mitochondrial Biology Unit, Hills Rd, Cambridge CB2 2XY, UK.
Partridge
Linda
L
Institute for Healthy Ageing, Department of Genes, Evolution and Environment, University College London, London WC1E 6BT, UK; Max Planck Institute for Biology of Ageing, Gleueler Strasse. 50 a, D-50931, Cologne, Germany.
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D031204:Caloric Restriction; D004032:Diet; D004331:Drosophila melanogaster / Q000254:growth & development* / Q000378:metabolism*; D005260:Female; D005453:Fluorescence; D017127:Glycation End Products, Advanced / Q000378:metabolism; D019476:Insect Proteins / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D016019:Survival Analysis; D013696:Temperature
D015415:Biomarkers; D017127:Glycation End Products, Advanced; D019476:Insect Proteins