Abstract
Ageing can be modulated by genetic as well as nutritional interventions. In female Drosophila melanogaster, lifespan is maximized at intermediate concentrations of sucrose as the carbohydrate source, and yeast as the protein source. Dampening the signal through the insulin/IGF signalling (IIS) pathway, by genetic ablation of median neurosecretory cells (mNSCs) that produce insulin-like peptides, extends lifespan and counteracts the detrimental effects of excess yeast. However, how IIS reduction impacts health on a high-sugar diet remains unclear. We find that, while the ablation of the mNSCs can extend lifespan and delay the age-related decline in the health of the neuromuscular system irrespective of the amount of dietary sugar, it cannot rescue the lifespan-shortening effects of excess sugar. On the other hand, ablation of mNSCs can prevent adult obesity resulting from excess sugar, and this effect appears independent from the canonical effector of IIS, dfoxo. Our study indicates that while treatments that reduce IIS have anti-ageing effects irrespective of dietary sugar, additional interventions may be required to achieve full benefits in humans, where excessive sugar consumption is a growing problem. At the same time, pathways regulated by IIS may be suitable targets for treatment of obesity.
Highlights
Ageing is the major risk factor for a number of killer and debilitating diseases, including cancer, cardiovascular disease and neurodegeneration [1]
With respect to mortality and age-related functional decline, we find that reduction in insulin/IGF signalling (IIS) achieved by the genetic ablation of median neurosecretory cells (mNSCs) can be beneficial on both standard and high-sugar diets; it cannot protect against the life-shortening effects of high sugar
We examined whether excess sugar can reduce the lifespan of flies mutated for the transcription factor (TF) that is the key effector of IIS for lifespan, dfoxo [19]
Summary
Ageing is the major risk factor for a number of killer and debilitating diseases, including cancer, cardiovascular disease and neurodegeneration [1]. When examining the survival of dfoxo null flies on two sugar concentrations (figure 1b and table 2), the initial model included ‘8Â sugar’ and ‘dfoxoD’ as covariates and their interaction, and was simplified by removing the non-significant interaction term. When looking at the TAG content in the ablation on two sugar concentrations (figure 3a and table 4), the initial model included ‘age’, ‘transgene’ and ‘8Â sugar’ as covariates, all of their pairwise interactions and the three-way interaction, and was simplified by sequentially removing non-significant. When looking at TAG in the ablation in the wild-type and dfoxo null backgrounds (figure 3b and table 5), the initial model included ‘age’, ‘transgene’ and ‘dfoxoD’ as covariates, all of their pairwise interactions and the three-way interaction, and was simplified by sequentially removing non-significant interaction terms. P 1⁄4 0.05 was used as the significance cut-off
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