Influence of spermidine on the mouse brain proteome
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Brain
SUBMITTER: 
Joern Dengjel
LAB HEAD: Joern Dengjel
PROVIDER: PXD022614 | Pride | 2021-04-15
REPOSITORIES: Pride
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Project description:Advanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that spermidine level was reduced in aged ovaries and supplementation of spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By micro-transcriptomic analysis, we further discovered that recovery of oocyte quality by spermidine was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this action mechanism was conserved in porcine oocytes under oxidative stress. Altogether, our findings demonstrate that spermidine supplementation is a potentially effective strategy to ameliorate oocyte quality and reproductive outcome of women at an advanced age.
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Project description:The polyamines putrescine, spermidine and spermine are ubiquitous metabolites synthesized in all cells. The intracellular levels of polyamines, especially spermidine, decrease in aging. Oral spermidine supplementation has been reported to alleviate aspects of aging-related disease in animal models, including decline in learning and memory. The diverse health benefits of spermidine supplementation, often at doses that do not significantly alter spermidine levels of target organs, suggests that exogenous spermidine may have a common site of action, the gastrointestinal (GI) tract. To directly deliver spermidine to the GI tract with minimum impact on the global spermidine levels, we engineered the probiotic yeast Sacchromyces boulardii (Sb) to overproduce and secrete spermidine. We tested the effects of a spermidine-producing yeast strain (Sb576) on aging-associated learning and memory decline in an olfactory classical conditioning in Drosophila melanogaster. Feeding of newly eclosed flies of the wild-type (w1118) strain for 30 days with food supplemented with live Sb576, but not live wild-type Sb (SbWT) or free spermidine, reduced aging-associated short-term memory (STM) decline. Notably, Sb576 supplementation, but not SbWT or spermidine supplementation, of either young flies or old flies for only three days also enhanced STM without affecting locomotive ability. Furthermore, we showed that Sb576 supplementation also significantly reduced aging-associated STM decline in Dh31R, a mutant strain lacking the diuretic hormone 31 receptor, which exhibits compromised learning and memory. These results demonstrate that in situ production of spermidine by a synthetic biotic yeast in the GI tract can enhance STM, and further suggest a mechanism involving the gut-brain axis.
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Project description:Administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extends the lifespan of various model organisms including yeast, flies and worms. In ageing yeast, spermidine treatment triggeres epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), leading to induction of autophagy and thereby suppressing oxidative stress and necrosis. In order to further characterize the effects by spermidine supplementation of aging yeast cultures and to understand how global histone deacetylation affects gene transcription during aging, Affymetrix-based microarray analyses of three day old as well as ten day old cultures with and without administration of spermidine was performed.
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