Circulating microRNAs and cross sectional and longitudinal measurements of physical functioning and frailty: An explorative study in older twins.

Rossella La Grotta, Cecilie Agergaard Sørensen, Asmus Cosmos Skovgaard, Mikael Thinggaard, Serena Dato, Giuseppina Rose, Jonas Mengel-From, Mette Soerensen

Department of Biology, Ecology and Earth Sciences, University of Calabria, Via Pietro Bucci, Rende CS, Calabria 87036, Italy; Danish Twin Registry, and Research Unit for Epidemiology, Biodemography and Biostatistics, Department of Public Health, University of Southern Denmark, Campus Vej 55, Odense M 5320, Denmark. Electronic address: [email protected]. · pubmed

Paper

Abstract

During aging, physical functioning declines, and disability and frailty increase; phenotypes which are bidirectionally linked. MicroRNAs (miRNAs) are epigenetic regulators of various physiological processes and suggested aging biomarkers. Here we investigate the association between circulating plasma miRNAs and hand grip strength, chair stand, (Rockwood) frailty, and activity of daily living (ADL) in 86 monozygotic twins (73-88 years). In cross-sectional analysis, both individual and twin-pair level analyses were performed, the latter controlling genetic confounding. The majority (74-100 %) of miRNAs identified in the individual-level analysis were validated by twin-pair-level analysis, with 14 miRNAs showing significance (p < 0.05) in both. Longitudinal analysis (up to eight years of follow-up) yielded more significant results (75-93 miRNAs), indicating that miRNAs might be more accurate in predicting functional decline over time. Of these miRNAs, seven showed consistent directions of effects across phenotypes. For all analyses, most (65-79 %) of the observed effect sizes were negative, reflecting reduced functionality with increased miRNA levels. Enrichment analyses revealed pathways of gene expression (incl. p53- and FOXO-mediated transcription), signal transduction, the immune system, metabolism of RNA, among others. Of specific miRNAs, miR-1274a demonstrated negative association in both cross-sectional and longitudinal investigations of ADL. These findings support miRNAs as biomarkers of age-related functional decline.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper claims that circulating microRNAs are associated with physical functioning and frailty in older adults, suggesting their potential as biomarkers for age-related functional decline. This research is relevant as it explores biological markers that could help understand and potentially mitigate the root causes of aging and functional decline, rather than merely addressing symptoms.

Author of this paper? Send a correction.