Centenarians, but not octogenarians, up-regulate the expression of microRNAs

Serna, Eva; Gambini, Juan; Borrás, Consuelo; Abdelaziz, Kheira M.; Belenguer, Ángel; Sanchís, Paula; Avellana, Juan A.; Rodríguez‐Mañas, Leocadio; Viña, José

doi:10.1038/srep00961

Cited by 90 publications

(75 citation statements)

References 24 publications

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“…Nine miRNAs had correlations with p values<0.05 (Table 3). Four of these miRNAs (miR-374, 376, 29, 378) have been shown in prior studies to be differentially expressed between older and younger persons in separate profiling experiments [18, 20, 21]. miR-374 was also downregulated in older participants in an earlier study [18], but in contrast with our study, miR-376 was upregulated in older participants in another report [20].…”

Section: Discussioncontrasting

confidence: 83%

“…Because miRNAs and aging genetic pathways are conserved from nematodes to humans, an increasing number of human miRNA studies have been carried out over the past several years. These studies have shown differential abundance of multiple miRNAs in peripheral blood mononuclear cells (PBMCs) or serum/plasma when comparing younger and older adults [16–21]. Sredni et al found that changes in global miRNA levels, but not in mRNA levels, are associated with healthy aging in young adult women [16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA)

Smith-Vikos

Liu

Parsons

et al. 2016

Aging

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In C. elegans, miRNAs are genetic biomarkers of aging. Similarly, multiple miRNAs are differentially expressed between younger and older persons, suggesting that miRNA-regulated biological mechanisms affecting aging are evolutionarily conserved. Previous human studies have not considered participants' lifespans, a key factor in identifying biomarkers of aging. Using PCR arrays, we measured miRNA levels from serum samples obtained longitudinally at ages 50, 55, and 60 from 16 non-Hispanic males who had documented lifespans from 58 to 92. Numerous miRNAs showed significant changes in expression levels. At age 50, 24 miRNAs were significantly upregulated, and 73 were significantly downregulated in the long-lived subgroup (76-92 years) as compared with the short-lived subgroup (58-75 years). In long-lived participants, the most upregulated was miR-373-5p, while the most downregulated was miR-15b-5p. Longitudinally, significant Pearson correlations were observed between lifespan and expression of nine miRNAs (p value<0.05). Six of these nine miRNAs (miR-211-5p, 374a-5p, 340-3p, 376c-3p, 5095, 1225-3p) were also significantly up- or downregulated when comparing long-lived and short-lived participants. Twenty-four validated targets of these miRNAs encoded aging-associated proteins, including PARP1, IGF1R, and IGF2R. We propose that the expression profiles of the six miRNAs (miR-211-5p, 374a-5p, 340-3p, 376c-3p, 5095, and 1225-3p) may be useful biomarkers of aging.

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Section: Discussioncontrasting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA)

Smith-Vikos

Liu

Parsons

et al. 2016

Aging

View full text Add to dashboard Cite

show abstract

“…mRNA and miRNA expression profiles of different human tissues during aging reveal the existence of a common pattern of defined transcriptional and epigenetic changes as well as tissue-specific age-related alterations (ElSharawy et al, 2012; Li et al, 2009; Maes et al, 2009; Ren et al, 2012; Santarosa et al, 2009; Serna et al, 2012). …”

Section: Hallmarks Of Cellular Senescencementioning

confidence: 99%

Are there roles for brain cell senescence in aging and neurodegenerative disorders?

et al. 2014

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The term cellular senescence was introduced more than five decades ago to describe the state of growth arrest observed in aging cells. Since this initial discovery, the phenotypes associated with cellular senescence have expanded beyond growth arrest to include alterations in cellular metabolism, secreted cytokines, epigenetic regulation and protein expression. Recently, senescence has been shown to play an important role in vivo not only in relation to aging, but also during embryonic development. Thus, cellular senescence serves different purposes and comprises a wide range of distinct phenotypes across multiple cell types. Whether all cell types, including post-mitotic neurons, are capable of entering into a senescent state remains unclear. In this review we examine recent data that suggest that cellular senescence plays a role in brain aging and, notably, may not be limited to glia but also neurons. We suggest that there is a high level of similarity between some of the pathological changes that occur in the brain in Alzheimer’s and Parkinson’s diseases and those phenotypes observed in cellular senescence, leading us to propose that neurons and glia can exhibit hallmarks of senescence previously documented in peripheral tissues.

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“…One such study found a signifi cant overlap of miRNA profi les in circulating mononuclear cells between centenarians and young individuals but not with octogenarians, by principle component analysis (Serna et al 2012 ). The small ncRNA included 7 species up-regulated in centenarians compared to young individuals and 102 as compared to octogenarians.…”

Section: Mirna Aging and Longevitymentioning

confidence: 98%

The Epigenome and Aging

Kim

Jazwinski

2015

Molecular and Integrative Toxicology

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The epigenetics of aging is a relatively new fi eld. Global DNA methylation has been examined for some time; however, only recently have age-related differentially methylated regions been elaborated. These regions encompass genes that in some cases interact with longevity and disease-associated genes. Histone modifi cations have now become of interest in aging studies. Model organisms have provided substantial evidence that some of the enzymes that are involved in histone modifi cations play a role in longevity, and direct evidence of such a role for one of the sirtuins has been gathered in mice. A number of studies examining expression of microRNA during aging in various organisms, including human, point to the possibility that these gene regulatory molecules may also be involved in aging. A recent study of one such microRNA in mice substantiates such a role in cardiac aging. All of these epigenetic mechanisms are responsive to environmental and lifestyle factors. Thus, the groundwork has been laid for an understanding of the interface between the genome and the environment that epigenetic mechanisms provide.

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Centenarians, but not octogenarians, up-regulate the expression of microRNAs

Cited by 90 publications

References 24 publications

A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA)

A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA)

Are there roles for brain cell senescence in aging and neurodegenerative disorders?

The Epigenome and Aging

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