Biomarkers of aging in Drosophila

Abstract

Summary 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. DR thus does not slow accumulation of ageing-related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of ageing-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 ageing-related damage. Using this approach, we assessed several commonly used biomarkers of ageing-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 ageing-related damage in flies. In contrast, five oxidised 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 ageing-related damage. Our approach provides a powerful method for identification of biomarkers of ageing.

Longevity of insulin receptor substrate1 null mice is not associated with increased basal antioxidant protection or reduced oxidative damage

“…While limited antioxidant parameters were affected by age, we did see age-related changes in oxidative damage (i.e., protein carbonyls and 4-HNE), although the direction of the age-related changes was not consistent between different tissues and different markers (Jacobson et al 2010). Protein carbonyl content increased with advancing age in brains of Ames dwarf mice, whereas age had no effect on hepatic protein carbonyls (Brown-Borg et al 2001).…”

Effects of aging and reproduction on protein quality control in soma and gametes of Drosophila melanogaster

“…Carbonylation of proteins has previously been shown to gradually increase with the age of different organisms, including D. melanogaster (see e.g., (Levine, 2002;Jacobson et al, 2010). To evaluate whether protein damage differs among body parts in aged, but not yet dying female flies with a reproductive potential, a quantitative analysis of the distribution of carbonylated proteins among body parts in the whole fly was performed.…”

“…The efficiency of this network declines gradually during aging (Koga et al, 2011), and many tissues of aged organisms show signs of failure in the control of protein homeostasis. This includes progressive accumulation of aberrant protein species in the form of oxidized proteins [e.g., carbonyl-and 4-hydroxynonenal (HNE)-modified proteins], advanced glycation end-product (AGE)-modified proteins, protein aggregates, amyloids, and inclusion bodies (Levine, 2002;Nyströ m, 2005;Friguet, 2006;Demontis & Perrimon, 2010;Jacobson et al, 2010;Koga et al, 2011). Intriguingly, boosting protein quality control functions by genetic means has, in some cases, been shown to postpone the development of age-related protein conformational disorders, such as neurodegenerative disorders (Balch et al, 2008), and even to extend the lifespan of some model organisms (Hsu et al, 2003).…”

Grasshopper Lazarillo, a GPI-anchored Lipocalin, increases Drosophila longevity and stress resistance, and functionally replaces its secreted homolog NLaz

“…Fluorescent AGEs are reliable biomarkers of aging-related damage. They track the effects of factors that condition mortality rates (e.g., temperature in the case of ectothermic animals like Drosophila), but are irreversible and thus not affected by other potentially reversing factors like dietary restriction (Jacobson et al, 2010). If the lack of NLaz does impose a basal stress in the tissues, we should expect an accelerated aging occurring in the null mutant flies.…”