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

Smith-Vikos, Thalyana; Liu, Zuyun; Parsons, Christine; Gorospe, Myriam; Ferrucci, Luigi; Gill, Thomas J.; Slack, Frank J.

doi:10.18632/aging.101106

Cited by 59 publications

(49 citation statements)

References 41 publications

(49 reference statements)

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“…We have also systematically adjusted for age, which is known to greatly influence the variations in the level of circulating miRNAs. (37)(38)(39)(40)(41) There may be several explanations for the discrepancies between the previously published studies and the present results. First, we systematically adjusted for age, which was not always performed in other studies.…”

Section: Discussioncontrasting

confidence: 98%

Lack of Association Between Select Circulating miRNAs and Bone Mass, Turnover, and Fractures: Data From the OFELY Cohort

et al. 2019

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Postmenopausal osteoporosis is characterized by the occurrence of fragility fracture with an increase in morbidity and mortality. Recently, microRNAs (miRNAs) have raised interest as regulators of translational repression, mediating a number of key processes, including bone tissue in both physiological and diseased states. The aim of this study was to examine the serum levels of 32 preselected miRNAs with reported function in bone and their association with osteoporotic fracture. We performed cross-sectional and longitudinal analyses from the OFELY Cohort. Serum levels of the miRNAs were quantified by qRT-PCR in 682 women: 99 premenopausal and 583 postmenopausal women, with 1 and 122 women with prevalent fragility fractures in each group, respectively. We have collected clinical variables (such as age, prevalent, and incident fractures), bone turnover markers (BTMs), BMD by dual X-ray absorptiometry, and bone microarchitecture with HRpQCT. We observed a number of miRNAs to be associated with fragility fractures (prevalent or incident), BTMs, BMD, and microarchitecture. This effect, however, was negated after age adjustment. This may be because age was also strongly associated with the serum levels of the 32 miRNAs (correlation coefficient up to 0.49), confirming previous findings. In conclusion, in a well-characterized prospective cohort with a sizeable sample size, we found no evidence that these 32 preselected miRNAs were not associated with BTMs, BMD, microarchitecture, and or fragility fractures. Ã CTX, mg/L (min-max) 0.466 (0.057-1.470) 0.374 (0.107-1.030) 0.481 (0.057-1.470) Ã Osteocalcin, ng/mL (min-max) Ã Ã p value considered as significant if <0.05. Tt.vBMD ¼ total volumetric bone mineral density; Ct.vBMD ¼ cortical volumetric bone mineral density; Tb.vBMD ¼ trabecular volumetric bone mineral density; BAP ¼ bone alkaline phosphatase. Journal of Bone and Mineral Research LACK OF ASSOCIATION BETWEEN miRNAs AND BONE: DATA FROM THE OFELY COHORT 5 FEURER ET AL. Ã Radius Tt.vBMD, mg/cm 3 (min-max) 245.6 (122.9-482.1) 278.1 (101.9-515.8) Ã Radius Ct.vBMD, mg/cm 3 (min-max) 771.9 (556.9-956.4) 803.0 (572.6-1004.8) Ã Radius Tb.vBMD, mg/cm 3 (min-max) 123.2 (50.3-264.0) 141.8 (17.5-262.8) Ã Tibia Tt.vBMD, mg/cm 3 (min-max) 228.3 (124.2-371.2) 252.8 (109.0-417.4) Ã Tibia Ct.vBMD, mg/cm 3 (min-max) 702.6 (437.7-912.7) 744.6 (376.7-976.6) Ã Tibia Tb.vBMD, mg/cm 3 (min-max) 133.6 (52.0-212.6) 149.3 (31.9-254.7) Ã CTX, mg/L (min-max) 0.463 (0.057-1.16) 0.484 (0.062-1.470) NS Osteocalcin, ng/mL (min-max) 28.6 (4.2-90.2) 27.7 (6.5-86.2) NS P1NP, ng/mL (min-max) 49.0 (8.1-138.6) 21.5 (10.0-139.7) NS BAP, UI/L (min-max) 39.3 (15.2-69.4) 38.8 (10.1-88.6) NS Ã p-value considered as significant if <0.05. Tt.vBMD ¼ total volumetric bone mineral density; Ct.vBMD ¼ cortical volumetric bone mineral density; Tb.vBMD ¼ trabecular volumetric bone mineral density; BAP ¼ bone alkaline phosphatase. 8 FEURER ET AL.

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“…Finally, it is possible that the effects we see may derive from differences between the strains unrelated to longevity. However, evidence suggests that there are links between both miR-664-3p and miR-203-3p and lifespan in human studies3235, suggesting that unrelated strain differences alone probably do not account for our observations, at least for these microRNAs.…”

Section: Discussionmentioning

confidence: 60%

MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice

Lee

Buric

George-Pandeth

et al. 2017

Sci Rep

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MicroRNAs (miRNAs) are small non-coding RNA species that have been shown to have roles in multiple processes that occur in higher eukaryotes. They act by binding to specific sequences in the 3’ untranslated region of their target genes and causing the transcripts to be degraded by the RNA-induced silencing complex (RISC). MicroRNAs have previously been reported to demonstrate altered expression in several aging phenotypes such as cellular senescence and age itself. Here, we have measured the expression levels of 521 small regulatory microRNAs (miRNAs) in spleen tissue from young and old animals of 6 mouse strains with different median strain lifespans by quantitative real-time PCR. Expression levels of 3 microRNAs were robustly associated with strain lifespan, after correction for multiple statistical testing (miR-203-3p [β-coefficient = −0.6447, p = 4.8 × 10−11], miR-664-3p [β-coefficient = 0.5552, p = 5.1 × 10−8] and miR-708-5p [β-coefficient = 0.4986, p = 1.6 × 10−6]). Pathway analysis of binding sites for these three microRNAs revealed enrichment of target genes involved in key aging and longevity pathways including mTOR, FOXO and MAPK, most of which also demonstrated associations with longevity. Our results suggests that miR-203-3p, miR-664-3p and miR-708-5p may be implicated in pathways determining lifespan in mammals.

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“…Many of our identified miRNAs were previously shown to be differentially expressed in relation to age in whole blood (ElSharawy et al ., 2012), PBMCs (Noren Hooten et al ., 2010), and serum (Noren Hooten et al ., 2013; Zhang et al ., 2014; Smith‐Vikos et al ., 2016). For example, miR‐130b‐5p (the second most significant miRNA in our study) was previously reported to be negatively associated with age in serum (Zhang et al ., 2014).…”

Section: Discussionmentioning

confidence: 99%

“…For example, miR‐130b‐5p (the second most significant miRNA in our study) was previously reported to be negatively associated with age in serum (Zhang et al ., 2014). In addition, miR‐340‐3p was reported to be significantly downregulated in long‐lived individuals vs. short‐lived individuals (Smith‐Vikos et al ., 2016). In mouse studies, miR‐130b‐5p was shown to regulate cholesterol and triglyceride homeostasis (Wagschal et al ., 2015).…”

Section: Discussionmentioning

confidence: 99%

Age-associated microRNA expression in human peripheral blood is associated with all-cause mortality and age-related traits

et al. 2017

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SummaryRecent studies provide evidence of correlations of DNA methylation and expression of protein‐coding genes with human aging. The relations of microRNA expression with age and age‐related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole‐blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 × 10−4 (Bonferroni‐corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age‐associated mRNA expression possibly driven by age‐associated microRNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict ‘microRNA age’ that incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2), suggesting that microRNA age may complement mRNA and epigenetic age prediction models. We used the difference between microRNA age and chronological age as a biomarker of accelerated aging (Δage) and found that Δage was associated with all‐cause mortality (hazards ratio 1.1 per year difference, P = 4.2 × 10−5 adjusted for sex and chronological age). Additionally, Δage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a microRNA age prediction model based on whole‐blood microRNA expression profiling. Age‐associated microRNAs and their targets have potential utility to detect accelerated aging and to predict risks for age‐related diseases.

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“…i.e. long and short –lived, and a lifespan signature of c-miRs was proposed (miR-211-5p, 374a-5p, 340-3p, 376c-3p, 5095, 1225-3p) (Smith-Vikos et al, 2016). This work highlights the possibility to trace healthy and unhealthy trajectories starting at a critical age when the evolution driving force is decreased and age-related diseases start to develop, and concomitantly gene expression regulation is less finely tuned.…”

Section: Circulating Mirs As Biomarkers Of Healthy and Unhealthy Amentioning

confidence: 99%

Circulating miRNAs and miRNA shuttles as biomarkers: Perspective trajectories of healthy and unhealthy aging

Olivieri

Capri

Bonafè

et al. 2017

Mechanisms of Ageing and Development

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Human aging is a lifelong process characterized by a continuous trade-off between pro-and anti-inflammatory responses, where the best-adapted and/or remodeled genetic/epigenetic profile may develop a longevity phenotype. Centenarians and their offspring represent such a phenotype and their comparison to patients with age-related diseases (ARDs) is expected to maximize the chance to unravel the genetic makeup that better associates with healthy aging trajectories. Seemingly, such comparison is expected to allow the discovery of new biomarkers of longevity together with risk factor for the most common ARDs. MicroRNAs (miRNAs) and their shuttles (extracellular vesicles in particular) are currently conceived as those endowed with the strongest ability to provide information about the trajectories of healthy and unhealthy aging. We review the available data on miRNAs in aging and underpin the evidence suggesting that circulating miRNAs (and cognate shuttles), especially those involved in the regulation of inflammation (inflamma-miRs) may constitute biomarkers capable of reliably depicting healthy and unhealthy aging trajectories.

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

Cited by 59 publications

References 41 publications

Lack of Association Between Select Circulating miRNAs and Bone Mass, Turnover, and Fractures: Data From the OFELY Cohort

MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice

Age-associated microRNA expression in human peripheral blood is associated with all-cause mortality and age-related traits

Circulating miRNAs and miRNA shuttles as biomarkers: Perspective trajectories of healthy and unhealthy aging

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