Hospitalized patients in internal medicine have an increased risk of low physical reserve which further declines during the hospital stay. The diagnosis requires bed-side testing of functional domains or more complex investigations of the muscle mass. Clinically useful biomarkers of functional status are needed, thus we aimed to explore the potential of microRNAs. Among hospitalized patients, we recorded the basic demographics, anthropometrics, nutritional status, and physical function domains: hand-grip strength (HGS, abnormal values M<30 kg, W<20 kg), balance (<30 s), chair-stands speed (CHSS<0.5/s) and gait speed (GS<0.8 m/s). A panel of five micro-RNAs (miRNA 1, miRNA 133a, miRNA 133b, miRNA 29a, miRNA 29b) and basic blood biochemistry and vitamin D values were recorded. We enrolled 80 patients (M40, W40), with a mean age of 68.8±8.4 years. Obesity was observed in 27.5 % and 30 %, low HGS and low CHSS in 65.0, 77.5 %, and 80, 90 % of men and women respectively. The median hospital stay was 6.5 days. MiRNA29a and miRNA29b have the strongest correlation with the triceps skinfold (miRNA 29b, r=0.377, p=0.0006) and CHSS (miRNA 29a, r=0.262, p=0.02). MiRNA 29a, miRNA 29b and 133a levels were significantly higher in patients with CHSS<0.5/s. Other anthropometric parameters, mobility domains, or vitamin D did not correlate. All miRNAs except of miRNA 1, could predict low CHSS (miRNA29b, AUROC=0.736 CI 0.56-0.91, p=0.01), particularly in patients with low HGS (miRNA 29b, AUROC=0.928 CI 0.83-0.98). Among hospitalized patients in internal medicine, low functional status was frequent. MicroRNAs were fair biomarkers of the antigravity domain, but not other domains. Larger studies with clinical endpoints are needed.

5th Department of Internal Medicine Comenius University Faculty of Medicine University Hospital Bratislava Slovak Republic

Zobrazit více v PubMed

BROWN DM, GOLJANEK-WHYSALL K. microRNAs: Modulators of the underlying pathophysiology of sarcopenia? Ageing Res Rev. 2015;24:263–273. doi: 10.1016/j.arr.2015.08.007. PubMed DOI

CHEN JF, MANDEL EM, THOMSON JM, WU Q, CALLIS TE, HAMMOND SM, CONLON FL, WANG DZ. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Gen. 2006;38:228–233. doi: 10.1038/ng1725. PubMed DOI PMC

CHEN X, MAO G, LENG SX. Frailty syndrome: an overview. Clin Interv Aging. 2014;9:433–441. doi: 10.2147/CIA.S45300. PubMed DOI PMC

COLLARD RM, BOTER H, SCHOEVERS RA, OUDE VOSHAAR RC. Prevalence of frailty in community-dwelling older persons: a systematic review. J Am Geriatr Soc. 2012;60:1487–1492. doi: 10.1111/j.1532-5415.2012.04054.x. PubMed DOI

CRUZ-JENTOFT AJ, BAHAT G, BAUER J, BOIRIE Y, BRUYERE O, CEDERHOLM T, COOPER C, LANDI F, ROLLAND Y, SAYER AA, SCHNEIDER SM, SIEBER CC, TOPINKOVA E, VanDe WOUDE M, VISSER M, ZAMBONI M. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:16–31. doi: 10.1093/ageing/afy169. PubMed DOI PMC

CUNHA AIL, VERONESE N, De MELO BORGES S, RICCI NA. Frailty as a predictor of adverse outcomes in hospitalized older adults: A systematic review and meta-analysis. Ageing Res Rev. 2019;56:100960. doi: 10.1016/j.arr.2019.100960. PubMed DOI

DELONG ER, DELONG DM, CLARKE-PEARSON DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–845. PubMed

DENT E, MORLEY JE, CRUZ-JENTOFT AJ, WOODHOUSE L, RODRÍGUEZ-MAÑAS L, FRIED LP, WOO J, APRAHAMIAN I, SANFORD A, LUNDY J, LANDI F, BEILBY J, MARTIN FC, BAUER JM, FERRUCCI L, MERCHANT RA, DONG B, ARAI H, HOOGENDIJK EO, WON CW, ABBATECOLA A, CEDERHOLM T, STRANDBERG T, GUTIÉRREZ ROBLEDO LM, FLICKER L, BHASIN S, AUBERTIN-LEHEUDRE M, BISCHOFF-FERRARI HA, GURALNIK JM, MUSCEDERE J, PAHOR M, RUIZ J, NEGM AM, REGINSTER JY, WATERS DL, VELLAS B. Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management. J Nutr Health Aging. 2019;23:771–787. doi: 10.1007/s12603-019-1273-z. PubMed DOI PMC

DLOUHÁ D, HUBÁČEK JA. Regulatory RNAs and cardiovascular disease - with a special focus on circulating microRNAs. Physiol Res. 2017;66:S21–S38. doi: 10.33549/physiolres.933588. PubMed DOI

GAŽOVÁ A, SAMÁKOVÁ A, LACZO E, HAMAR D, POLÁKOVIČOVÁ M, JURIKOVÁ M, KYSELOVIČ J. Clinical utility of miRNA-1, miRNA-29g and miRNA-133s plasma levels in prostate cancer patients with high-intensity training after androgen-deprivation therapy. Physiol Res. 2019;68:S139–S147. doi: 10.33549/physiolres.934298. PubMed DOI

GINGRICH A, VOLKERT D, KIESSWETTER E, THOMANEK M, BACH S, SIEBER CC, ZOPF Y. Prevalence and overlap of sarcopenia, frailty, cachexia and malnutrition in older medical inpatients. BMC Geriatrics. 2019;19:120. doi: 10.1186/s12877-019-1115-1. PubMed DOI PMC

GOLJANEK-WHYSALL K, IWANEJKO LA, VASILAKI A, PEKOVIC-VAUGHAN V, Mc DONAGH B. Ageing in relation to skeletal muscle dysfunction: redox homoeostasis to regulation of gene expression. Mam Genome. 2016;27:341–357. doi: 10.1007/s00335-016-9643-x. PubMed DOI PMC

HE N, ZHANG YL, ZHANG Y, FENG B, ZHENG Z, WANG D, ZHANG S, GUO Q, YE H. Circulating MicroRNAs in plasma decrease in response to sarcopenia in the elderly. Front Genet. 11:167–2020. doi: 10.3389/fgene.2020.00167. PubMed DOI PMC

HILTON C, NEVILLE MJ, WITTEMANS LBL, TODORCEVIC M, PINNICK KE, PULIT SL, LUAN J, KULYTÉ A, DAHLMAN I, WAREHAM NJ, LOTTA LA, ARNER P, LINDGREN CM, LANGENBERG C, KARPE F. MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix composition. EBioMedicine. 2019;44:467–475. doi: 10.1016/j.ebiom.2019.05.047. PubMed DOI PMC

IANNONE F, MONTESANTO A, CIONE E, CROCCO P, CAROLEO MC, DATO S, ROSE G, PASSARINO G. Expression patterns of muscle-specific miR-133b and miR-206 correlate with nutritional status and sarcopenia. Nutrients. 2020;12:297. doi: 10.3390/nu12020297. PubMed DOI PMC

IPSON BR, FLETCHER MB, ESPINOZA SE, FISHER AL. Identifying exosome-derived MicroRNAs as candidate biomarkers of frailty. J Frailty Aging. 2018;7:100–103. doi: 10.14283/jfa.2017.45. PubMed DOI PMC

LIU HC, HAN DS, HSU CC, WANG JS. Circulating MicroRNA-486 and MicroRNA-146a serve as potential biomarkers of sarcopenia in the older adults. BMC Geriatrics. 2021;21:86. doi: 10.1186/s12877-021-02040-0. PubMed DOI PMC

MURABITO JM, RONG J, LUNETTA KL, HUAN T, LIN H, ZHAO Q, FREEDMAN JE, TANRIVERDI K, LEVY D, LARSON MG. Cross-sectional relations of whole-blood miRNA expression levels and hand grip strength in a community sample. Aging Cell. 2017;16:888–894. doi: 10.1111/acel.12622. PubMed DOI PMC

NIE M, DENG ZL, LIU J, WANG DZ. Noncoding RNAs, emerging regulators of skeletal muscle development and diseases. BioMed Res Int. 2015:676575. doi: 10.1155/2015/676575. PubMed DOI PMC

O’CAOIMH R, GALLUZZO L, RODRÍGUEZ-LASO ÁVan Der HEYDEN J, RANHOFF AH, LAMPRINI-KOULA M, CIUTAN M, LÓPEZ-SAMANIEGO L, CARCAILLON-BENTATA L, KENNELLY S, LIEW A. Prevalence of frailty at population level in European ADVANTAGE Joint Action Member States: a systematic review and meta-analysis. Annali Dell’Istituto Superiore Di Sanita. 2018;54:226–238. PubMed

OLIVEIRA JS, PINHEIRO MB, FAIRHALL N, WALSH S, CHESTERFIELD FRANKS T, KWOK W, BAUMAN A, SHERRINGTON C. Evidence on physical activity and the prevention of frailty and sarcopenia among older people: a systematic review to inform the world health organization physical activity guidelines. J Phys Activity Health. 2020;17:1247–1258. doi: 10.1123/jpah.2020-0323. PubMed DOI

PAPADOPOULOU SK. Sarcopenia: a contemporary health problem among older adult populations. Nutrients. 2020;12:1293. doi: 10.3390/nu12051293. PubMed DOI PMC

PICCA A, CALVANI R, CESARI M, LANDI F, BERNABEI R, COELHO-JÚNIOR HJ, MARZETTI E. Biomarkers of physical frailty and sarcopenia: coming up to the place? Int J Mol Sci. 2020;21:5635. doi: 10.3390/ijms21165635. PubMed DOI PMC

SKLADANÝ Ľ, KASSOVÁ S, ŠVÁČ J. Frailty syndrome in internal medicine (Article in Slovak) Intern med. 2018;18:283–286.

VRBOVÁ P, KOLLER T, PAYER J. Sarcopenia in internal medicine. Via Practica. 2019;16:58–60.

WORLD HEALTH ORGANIZATION. WHO Clinical Consortium on Healthy Ageing. In: Araujo de Carvalho I, Beard J, Thiyagarajan JA, Sumi Y, editors. Topic focus: frailty and intrinsic capacity. WHO; Geneva: 2017. pp. 3–11.

YANAI K, KANEKO S, ISHII H, AOMATSU A, ITO K, HIRAI K, OOKAWARA S, ISHIBASHI K, MORISHITA Y. MicroRNAs in sarcopenia: a systematic review. Front Med. 2020;7:180. doi: 10.3389/fmed.2020.00180. PubMed DOI PMC