Spermidine based ameliration of Age-dependent memory impairment under the paradigMS of enhanced autophagy and altered epigenome in Drosophila melanogaster

Abstract

Aging, the process of growing old, involves gradual biological impairment of normal function probably as a result of changes made to cells and structural components which ultimately affect the organismas a whole. Among multiple biochemical correlates of aging, a decrease in endogenous polyamines has been associated with aging, although, it is still not understood if this is the cause or consequence of aging. External administration of spermidine restores the endogenous spermidine levels and promotes longevity in several model organisms including yeast, worms, flies, mice and human cell lines.A decrease in polyamine levels has been observed in memory associated structures and this could be causally associated to age associated memory impairment. Evidences from previous studies and data from the Sigrist lab suggest that spermidine administration ameliorates age-dependent memory impairment. Here, we suggest that spermidine might improve memory by preventing age-dependent accumulation of ubiquitinated proteins by upregulation of autophagy in fly heads. Also, cognitive decline with age has been attributed to epigenetic changes like changes in acetylation status of different histones. Therefore, as the second part of this study I tried to characterize Drosophila histone mutants in terms of longevity and learning performance. Preliminary results obtained from these assays suggest a possible role of Histone 3 locus in regulating life span and learning and memory formation in flies, whereas the flies carrying the point mutation in H3-K27 lived a normal lifespan and had memory performance just like wild-type flies.