Biology subjects

Kujala, U. M.

Publications and source records attributed to Kujala, U. M..

4 recordsLinked to original sources

bioRxiv2023

Menopausal transition alters female skeletal muscle transcriptome

Menopause is associated with unfavorable changes in body composition. Skeletal muscle cells are targets of hormonal regulation and are affected by the interplay between coding and non-coding RNAs. Muscle transcriptome, including messenger-RNA (mRNA), long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) has not previously been studied in women during the menopausal transition. Thus, we took a multi-RNA omics approach to get insight into transcriptome-wide events of menopause. Our study included baseline and follow-up muscle samples from seven early (EarlyMT) and 17 late perimenopausal (LateMT) women transitioning to early postmenopause during the study. Total RNA was sequenced and differential expression (DE) of the transcriptome was investigated. The potential gene functions were investigated with pathway analyses and protein level expression with Western Blot. We found 30 DE mRNA genes in EarlyMT and 19 in LateMT participating in pathways controlling cell death, growth, and interactions with external environment. Lack of protein level changes may indicate a specific role of the regulatory RNAs during menopause. Ten DE lncRNA transcripts were identified but did not result in DE lncRNAs genes. No DE miRNAs were found. Despite the lack of DE findings in regulatory RNAs, we identified putative regulatory networks, likely to be affected by estradiol availability. The changes in gene expression were correlated with observed changes in body composition variables, indicating muscularity and adiposity regulators to be affected by menopausal transition. In essence, the observed DE genes and their regulatory networks may offer novel mechanistic insights on factors affecting body composition during and after menopause.

molecular biology↗

bioRxiv2022

Age but not menopausal status is linked to lower resting energy expenditure

ContextIt remains uncertain whether aging before late adulthood and menopause are associated with fat-free mass and fat mass-adjusted resting energy expenditure (REEadj). ObjectivesWe investigated whether REEadj differs between middle-aged and younger women and between middle-aged women with different menopausal statuses. We repeated the age group comparison between middle-aged mothers and their daughters to partially control for genotype. We also explored whether serum estradiol and follicle-stimulating hormone concentrations explain REEadj in midlife. MethodsWe divided 120 women, including 16 mother-daughter pairs, into age groups; group I (n = 26) consisted of participants aged 17-21, group II (n = 35) of those aged 22-38 and group III (n = 59) of those aged 41-58 years. The women in group III were further categorized as pre- or perimenopausal (n = 19), postmenopausal (n = 30) or postmenopausal hormone therapy users (n = 10). REE was assessed using indirect calorimetry, body composition using dual-energy X-ray absorptiometry and hormones using immunoassays. ResultsThe REEadj of group I was 126 kcal/d (95% CI: 93-160) higher than that of group III, and the REEadj of group II was 88 kcal/d (95% CI: 49-127) higher. Furthermore, daughters had a 100 kcal/d (95% CI: 63-138 kcal/d) higher REEadj than their middle-aged mothers (all P < 0.001). In group III, REEadj was not lower in postmenopausal women and did not vary by sex hormone concentrations. ConclusionsWe demonstrated that REEadj declines with age in women before late adulthood, also when controlling partially for genetic background, and that menopause may not contribute to this decline.

physiology↗

bioRxiv2022

Extracellular vesicles and high-density lipoproteins: Exercise and estrogen-responsive small RNA carriers

Decreased systemic estrogen levels (i.e., menopause) affect metabolic health. However, the detailed mechanisms underlying this process remain unclear. Both estrogens and exercise have been shown to improve metabolic health, which may be partly mediated by circulating microRNA (c-miR) signaling. In recent years, extracellular vesicles (EV) have increased interest in the field of tissue crosstalk. However, in many studies on EV-carried miRs, the co-isolation of high-density lipoprotein (HDL) particles with EVs has not been considered, potentially affecting the results. Here, we demonstrate that EV and HDL particles have distinct small RNA (sRNA) content, including both host and nonhost sRNAs. Exercise caused an acute increase in relative miR abundancy in EVs, whereas in HDL particles, it caused an increase in transfer RNA-derived sRNA. Furthermore, we demonstrate that estrogen deficiency caused by menopause blunts acute exercise-induced systemic miR-response in both EV and HDL particles. HIGHLIGHTSO_LIExtracellular vesicles and HDL particles have a distinct sRNA content C_LIO_LIExtracellular vesicles and HDL particles carry both host and nonhost sRNA cargo C_LIO_LIEstrogen deficiency blunts the c-miR-response induced by acute exercise C_LIO_LIExercise responsive miRs in HT users may regulate the choice of energy substrate C_LI

molecular biology↗

bioRxiv2017

Long-Term Leisure-Time Physical Activity and Other Health Habits as Predictors of Objectively Monitored Late-Life Physical Activity: A 40-Year Twin Study

IMPORTANCEModerate-to-vigorous physical activity (MVPA) in old age is an important indicator of good health and functional capacity enabling independent living.\n\nOBJECTIVETo investigate whether physical activity and other health habits at ages 31-48 years predict objectively measured MVPA decades later.\n\nDESIGN, SETTING, AND PARTICIPANTSThis prospective twin cohort study in Finland comprised 616 individuals (197 complete twin pairs, including 91 monozygotic pairs, born 1940-1944), who responded to baseline questionnaires in 1975, 1981, and 1990, and participated in accelerometer monitoring at follow-up (mean age, 73 years).\n\nEXPOSURESPrimary exposure was long-term leisure-time physical activity, 1975-1990 (LT-mMET index). Covariates were body mass index (BMI), work-related physical activity, smoking, heavy alcohol use and health status in 1990, and socioeconomic status.\n\nMAIN OUTCOMES AND MEASURESPhysical activity was measured with a waist-worn triaxial accelerometer (at least 10 hours per day for at least 4 days) to obtain daily mean MVPA values.\n\nRESULTSHigh baseline LT-mMET index predicted higher amounts of MVPA (increase in R2 of 6.9% after age and sex adjustment, P<.001) at follow-up. After addition of BMI to the regression model, the R2 value of the whole multivariate model was 17.2%, and with further addition of baseline smoking, socioeconomic status, and health status, the R2 increased to 20.3%. In pairwise analyses, differences in MVPA amount were seen only among twin pairs who were discordant at baseline for smoking (n=40 pairs, median follow-up MVPA 25 vs. 35 min, P=.037) or for health status (n=69 pairs, 30 vs. 44 min, P=.014). For smoking, the difference in MVPA also was seen for monozygotic pairs, but for health status, it was seen only for dizygotic pairs. Mediation analysis showed that shared genetic factors explained 82% of the correlation between LT-mMET and MVPA.\n\nCONCLUSIONS AND RELEVANCELow leisure-time physical activity at younger age, overweight, smoking, low socioeconomic status, and health problems predicted low MVPA in old age in individual-based analyses. However, based on the pairwise analyses and quantitative trait modeling, genetic factors and smoking seem to be important determinants of later-life MVPA.

epidemiology↗