Advanced glycation end-products (AGEs) build up in our tissues over time and cause a range of issues, such as by gluing together important proteins, or triggering abnormal cell behavior. This is one of the contributing causes of degenerative aging, in fact. Many different types of AGE exist, some of which are hardier and longer-lasting than others, and levels of the various types swing up and down to different degrees in response to diet and other circumstances. There is some debate over the degree to which dietary AGE intake is important versus the creation of AGEs through metabolic processes taking place within the body. Here at least researchers show that higher levels of AGEs in the diet of flies leads to shorter lives:
Advanced glycation end product (AGEs)-modified proteins are formed by the non-enzymatic glycation of free amino groups of proteins and along with lipofuscin (a highly oxidized aggregate of covalently cross-linked proteins, sugars and lipids) have been found to accumulate during ageing and in several age-related diseases.
As the in vivo effects of diet-derived AGEs or lipofuscin remain elusive, we sought to study the impact of oral administration of glucose (Glc)-, fructose (Frc)-, or ribose (Rib)-modified albumin or of artificial lipofuscin (LF) in a genetically tractable model organism.
We report herein that continuous feeding of young Drosophila flies with culture medium enriched in AGEs or in lipofuscin resulted in reduced locomotor performance, in accelerated rates of AGEs-modified proteins and carbonylated proteins accumulation in the somatic tissues and the haemolymph of flies, as well as in a significant reduction of flies healthspan and lifespan. These phenotypic effects were accompanied with reduced proteasome peptidase activities in both the haemolymph and in somatic tissues of flies and higher levels of oxidative stress and proteasome expression levels.
Finally, RNAi-mediated cathepsin D knockdown reduced flies longevity and significantly augmented the deleterious effects of AGEs and lipofuscin indicating that lysosomal cathepsins reduce the toxicity of diet-derived AGEs or lipofuscin. Our in vivo studies demonstrate that chronic ingestion of AGEs or lipofuscin disrupt proteostasis and accelerate the functional decline that occurs with normal ageing.