Multi-level remodeling of transcriptional landscapes in aging and longevity

Abstract

In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and gene expression has been observed to be deregulated with aging. In this review, we discuss the current knowledge on the transcriptional alterations that have been described to occur with age in metazoans. First, we discuss age-related transcriptional changes in protein-coding genes, the expected functional impact of such changes, and how known pro-longevity interventions impact these changes. Second, we discuss the changes and impact of emerging aspects of transcription in aging, including age-related changes in splicing, lncRNAs and circRNAs. Third, we discuss the changes and potential impact of transcription of transposable elements with aging. Fourth, we highlight small ncRNAs and their potential impact on the regulation of aging phenotypes. Understanding the aging transcriptome will be key to identify important regulatory targets, and ultimately slow-down or reverse aging and extend healthy lifespan in humans.

Multi-omic profiling of primary mouse neutrophils reveals a pattern of sex and age-related functional regulation

“…Key predictors also included CG and CpG content in the promoter and gene sequences ( Figure 5C). This observation is consistent with our previous work identifying promoter CpG content as a top predictive feature of age-related gene expression across four male mouse tissues (Benayoun et al, 2019). Cytosines in CpG configurations are the primary targets of DNA methylation in mammalian cells (Rausch et al, 2020).…”

“…Indeed, neutrophil dysfunction in aging organisms may help drive aspects of age-related inflammatory phenotypes, including the neutrophils' ability to resolve inflammation, to undergo NETosis and to secrete proteases from their intracellular granules (Sapey et al, 2014;Tseng and Liu, 2014). Although changes in gene expression regulation throughout lifespan have been reported across many tissues and cell types (Benayoun et al, 2019;Lai et al, 2019), how organismal aging (rather than "daily" cellular aging) affects neutrophils remains largely unknown.…”

Correction of presbyopia: old problems with old (and new) solutions

“…The true long‐term solution, and where much of our future research likely may need to occur may be in preventing the onset of presbyopia in the first place . Or, better yet, maybe even preventing ageing from occurring in the first place? However, until then, a key understanding of the strengths and limitations of accommodation surrogates and how they might be applied in our clinical practices to aid our patients is critical.…”

Aging and Caloric Restriction Modulate the DNA Methylation Profile of the Ribosomal RNA Locus in Human and Rat Liver

“…Aging is a multi-dimensional, multi-factorial process [4], in which the organism continuously adapts to the progressive accumulation of damage and the decay in maintenance systems that occur over time [5,6]. Age-related changes have been described at the epigenomic [7,8], transcriptomic [9,10], and proteomic level [11][12][13]. Regarding the proteome, the observed changes are, in part, related to the diminished efficiency of the proteostasis machinery, which leads to the accumulation of damaged, misfolded and/or aggregated proteins [14].…”