Drosophila nervous system as a target of aging and anti-aging interventions

Omelyanchuk, L. V.; Shaposhnikov, Mikhail; Moskalev, Alexey

doi:10.3389/fgene.2015.00089

Cited by 11 publications

(9 citation statements)

References 46 publications

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“…This ultimately yielded several hundred candidate genes, which suggests the underlying genetic architecture for observed metabolomic differences is highly polygenic (Supplementary Table S3). This is in keeping with findings from experimental evolution studies in sexually reproducing eukaryotes and studies on the genetics of complex traits as a whole [21,85,86]. However, it is worth noting that focusing on genomic regions that best predict candidate metabolite differentiation narrowed candidates to hundreds of genes from thousands if we had relied solely on SNP differentiation between groups.…”

Section: Genomics To Metabolomicssupporting

confidence: 74%

Combining Metabolomics and Experimental Evolution Reveals Key Mechanisms Underlying Longevity Differences in Laboratory Evolved Drosophila melanogaster Populations

Phillips

Arnold

Vue

et al. 2022

IJMS

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Experimental evolution with Drosophila melanogaster has been used extensively for decades to study aging and longevity. In recent years, the addition of DNA and RNA sequencing to this framework has allowed researchers to leverage the statistical power inherent to experimental evolution to study the genetic basis of longevity itself. Here, we incorporated metabolomic data into to this framework to generate even deeper insights into the physiological and genetic mechanisms underlying longevity differences in three groups of experimentally evolved D. melanogaster populations with different aging and longevity patterns. Our metabolomic analysis found that aging alters mitochondrial metabolism through increased consumption of NAD+ and increased usage of the TCA cycle. Combining our genomic and metabolomic data produced a list of biologically relevant candidate genes. Among these candidates, we found significant enrichment for genes and pathways associated with neurological development and function, and carbohydrate metabolism. While we do not explicitly find enrichment for aging canonical genes, neurological dysregulation and carbohydrate metabolism are both known to be associated with accelerated aging and reduced longevity. Taken together, our results provide plausible genetic mechanisms for what might be driving longevity differences in this experimental system. More broadly, our findings demonstrate the value of combining multiple types of omic data with experimental evolution when attempting to dissect mechanisms underlying complex and highly polygenic traits such as aging.

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Section: Genomics To Metabolomicssupporting

confidence: 74%

Combining Metabolomics and Experimental Evolution Reveals Key Mechanisms Underlying Longevity Differences in Laboratory Evolved Drosophila melanogaster Populations

Phillips

Arnold

Vue

et al. 2022

IJMS

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“…Secondly, aging of the brain leads to onset and progression of neurological diseases, which accelerate and aggravate the aging process 29 . And finally, many transgenes have been identified that can increase lifespan when over-expressed in neurons 30 . Thus, the nervous system may be considered a key target of anti-aging interventions.…”

Section: Resultsmentioning

confidence: 99%

Lifespan and Stress Resistance in Drosophila with Overexpressed DNA Repair Genes

Shaposhnikov

Proshkina

Shilova

et al. 2015

Sci Rep

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DNA repair declines with age and correlates with longevity in many animal species. In this study, we investigated the effects of GAL4-induced overexpression of genes implicated in DNA repair on lifespan and resistance to stress factors in Drosophila melanogaster. Stress factors included hyperthermia, oxidative stress, and starvation. Overexpression was either constitutive or conditional and either ubiquitous or tissue-specific (nervous system). Overexpressed genes included those involved in recognition of DNA damage (homologs of HUS1, CHK2), nucleotide and base excision repair (homologs of XPF, XPC and AP-endonuclease-1), and repair of double-stranded DNA breaks (homologs of BRCA2, XRCC3, KU80 and WRNexo). The overexpression of different DNA repair genes led to both positive and negative effects on lifespan and stress resistance. Effects were dependent on GAL4 driver, stage of induction, sex, and role of the gene in the DNA repair process. While the constitutive/neuron-specific and conditional/ubiquitous overexpression of DNA repair genes negatively impacted lifespan and stress resistance, the constitutive/ubiquitous and conditional/neuron-specific overexpression of Hus1, mnk, mei-9, mus210, and WRNexo had beneficial effects. This study demonstrates for the first time the effects of overexpression of these DNA repair genes on both lifespan and stress resistance in D. melanogaster.

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“…The segments contain protein coding genes and microRNAs that are best candidates for further analyses aiming at pinpointing the identity of loci mediating the phenotype. Although analysis of variation in longevity among lines pointed to a segment containing the gene hep, a known factor associated with aging in Drosophila (Seong et al, 2001;Wang et al, 2003Wang et al, , 2005Paaby and Schmidt, 2009;Omelyanchuk et al, 2015), the genes residing in the segments associated with accelerated mortality post-reproduction are less amenable to functional interpretations. Male-female interactions can be experimentally modeled through a number of designs that themselves make the contribution of copulation, courting, diffusible compounds, ejaculate composition and/or other attributes more or less salient.…”

Section: Discussionmentioning

confidence: 99%

“…This 60 kb X-linked segment with higher probability of containing genetic factors that contribute to variation in aging among genotypes ( Figure 5) harbors 7 protein-coding genes. One of these genes is the protein-coding gene hemipterous (hep) that encodes a protein kinase that has long been known to affect aging in Drosophila (Seong et al, 2001;Wang et al, 2003Wang et al, , 2005Paaby and Schmidt, 2009;Omelyanchuk et al, 2015). In view of this observation we proceeded to investigate the association between reproductioninduced male mortality and genetic variation in the DSPR.…”

Section: Reproduction Accelerates Male Mortality In Drosophilamentioning

confidence: 99%

Reproductive activity triggers accelerated male mortality and decreases lifespan: genetic and gene expression determinants in Drosophila

Branco¹,

Schilling

Silkaitis

et al. 2016

Heredity

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Reproduction and aging evolved to be intimately associated. Experimental selection for early-life reproduction drives the evolution of decreased longevity in Drosophila whereas experimental selection for increased longevity leads to changes in reproduction. Although life history theory offers hypotheses to explain these relationships, the genetic architecture and molecular mechanisms underlying reproduction-longevity associations remain a matter of debate. Here we show that mating triggers accelerated mortality in males and identify hundreds of genes that are modulated upon mating in the fruit fly Drosophila melanogaster. Interrogation of genome-wide gene expression in virgin and recently mated males revealed coherent responses, with biological processes that are upregulated (testis-specific gene expression) or downregulated (metabolism and mitochondria-related functions) upon mating. Furthermore, using a panel of genotypes from the Drosophila Synthetic Population Resource (DSPR) as a source of naturally occurring genetic perturbation, we uncover abundant variation in longevity and reproduction-induced mortality among genotypes. Genotypes displayed more than fourfold variation in longevity and reproduction-induced mortality that can be traced to variation in specific segments of the genome. The data reveal individual variation in sensitivity to reproduction and physiological processes that are enhanced and suppressed upon mating. These results raise the prospect that variation in longevity and age-related traits could be traced to processes that coordinate germline and somatic function.

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Drosophila nervous system as a target of aging and anti-aging interventions

Cited by 11 publications

References 46 publications

Combining Metabolomics and Experimental Evolution Reveals Key Mechanisms Underlying Longevity Differences in Laboratory Evolved Drosophila melanogaster Populations

Combining Metabolomics and Experimental Evolution Reveals Key Mechanisms Underlying Longevity Differences in Laboratory Evolved Drosophila melanogaster Populations

Lifespan and Stress Resistance in Drosophila with Overexpressed DNA Repair Genes

Reproductive activity triggers accelerated male mortality and decreases lifespan: genetic and gene expression determinants in Drosophila

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