Abstract
BackgroundUnderstanding gene expression changes over lifespan in diverse animal species will lead to insights to conserved processes in the biology of aging and allow development of interventions to improve health. Rotifers are small aquatic invertebrates that have been used in aging studies for nearly 100 years and are now re-emerging as a modern model system. To provide a baseline to evaluate genetic responses to interventions that change health throughout lifespan and a framework for new hypotheses about the molecular genetic mechanisms of aging, we examined the transcriptome of an asexual female lineage of the rotifer Brachionus manjavacas at five life stages: eggs, neonates, and early-, late-, and post-reproductive adults.ResultsThere are widespread shifts in gene expression over the lifespan of B. manjavacas; the largest change occurs between neonates and early reproductive adults and is characterized by down-regulation of developmental genes and up-regulation of genes involved in reproduction. The expression profile of post-reproductive adults was distinct from that of other life stages. While few genes were significantly differentially expressed in the late- to post-reproductive transition, gene set enrichment analysis revealed multiple down-regulated pathways in metabolism, maintenance and repair, and proteostasis, united by genes involved in mitochondrial function and oxidative phosphorylation.ConclusionsThis study provides the first examination of changes in gene expression over lifespan in rotifers. We detected differential expression of many genes with human orthologs that are absent in Drosophila and C. elegans, highlighting the potential of the rotifer model in aging studies. Our findings suggest that small but coordinated changes in expression of many genes in pathways that integrate diverse functions drive the aging process. The observation of simultaneous declines in expression of genes in multiple pathways may have consequences for health and longevity not detected by single- or multi-gene knockdown in otherwise healthy animals. Investigation of subtle but genome-wide change in these pathways during aging is an important area for future study.
Highlights
Understanding gene expression changes over lifespan in diverse animal species will lead to insights to conserved processes in the biology of aging and allow development of interventions to improve health
Aging in B. manjavacas is characterized by large shifts in transcript abundance between major life stages (Table 1, Figs 2, 3 and 4), which we take as a first-order proxy for gene expression
Because gene set enrichment analysis (GSEA) uses only those transcripts that can be annotated to Human genome organization (HUGO) gene nomenclature committee (HGNC) and combines expression of transcript variants to show gene-level transcription, we examined aging-related KEGG-defined pathways using annotation defined by refseq and swissprot
Summary
Understanding gene expression changes over lifespan in diverse animal species will lead to insights to conserved processes in the biology of aging and allow development of interventions to improve health. Research from model systems has characterized a range of physiological and molecular phenotypes associated with aging. These include genomic instability caused by accumulation of DNA damage, dysregulation of repair mechanisms, and telomere attrition; epigenetic alterations; dysregulation of transcription; loss of proteostasis; cellular senescence; and deregulated nutrient sensing, metabolic pathways, and energy use (reviewed in [1]). Many of the genes and gene networks that modulate aging are conserved across animal phyla For this reason, Gribble and Mark Welch BMC Genomics (2017) 18:217 the highly tractable model systems Drosophila and Caenorhabditis have provided fundamental advances in our understanding of the genetic control of cellular processes that affect aging. Arthropods and nematodes are more closely related to each other than originally thought [10, 11], limiting the evolutionary range in comparative studies of aging [12] and the degree to which conclusions can be reliably generalized from these models to humans
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