Biology subjects

Mykkanen, J.

Publications and source records attributed to Mykkanen, J..

3 recordsLinked to original sources

bioRxiv2026

Male youth BMI is associated with epigenetic ageing of female descendants but not blood or sperm DNA methylation

Studies based on harvest records indicate that grandparental nutrition in youth is associated with the health traits of grandchildren in a sex-specific lineage. We investigated whether male early adulthood anthropometrics associate with epigenetic age, a measure of general well-being, and DNA methylation, a potential molecular inheritance mechanism, in three generations of descendants. Data on weight, height, BMI and chest circumference measured at military draft examinations (at age 18-24 yrs.) were retrieved from national archives for 1,013 men, herein referred to as Generation Archives (GA). The genome-wide DNA methylation of their descendants participating in the Young Finns Study (YFS) was measured from the blood and sperm from the children (59-80 yrs., nblood = 362, nsperm = 51), grandchildren (34-49 yrs., nblood = 421, nsperm = 98) and great-grandchildren (7-30 yrs., nblood = 200). The men's (GA) BMI had an inverse association with the epigenetic pace of ageing (DunedinPACE) of their daughters ({beta} = -0.01, p = 0.002, n = 169) and the daughters' daughters ({beta} = -0.01, p = 0.049, n = 126) but not with that of their male descendants. From within the YFS cohort, maternal, but not paternal, BMI at ages 13-34 also had an inverse association with the DunedinPACE of the immediate offspring. However, robust evidence for the inheritance mechanism was not found in the analyses between the anthropometric measurements of the GA men and the DNA methylation profiles in the blood and sperm of their descendants.

molecular biology↗

bioRxiv2025

Faecal transplantation from exuberant toddlers increases exploratory behaviour in rats

BackgroundBehavioural phenotypes have previously been transferred via faecal microbiota transplantation (FMT) from patients with psychiatric disorders to rodents. Studies indicate that the gut microbiota composition may be linked to certain temperament traits, defined as biologically-based differences in emotional reactivity and self-regulation. Here, we aimed to determine if the gut microbiota plays a role in temperament using an FMT approach. We focused on the temperament traits of exuberance, defined as positive reactivity, decreased behavioural inhibition, and high behavioural approach tendencies. MethodsFaeces from 2.5-year-old toddlers from FinnBrain Birth Cohort Study with high exuberance/approach or high behavioural inhibition in the LabTAB bubbles-episode was transferred to juvenile male Sprague Dawley rats (age 22/23 days). Behaviour of the rat recipients (n=53) was assessed using the novel non-social arena, novel social arena, hole board test for exploratory behaviour, social approach-avoidance test, and forced swim test. The faecal pellets collected from the rodents were analyzed with 16s rRNA sequencing and faecal samples from the sample of toddlers (which included the donors, n=176) were analysed using short-read metagenomic sequencing. The striatum and prefrontal cortex from the rodents brains were analysed post-mortem using RNAseq. ResultsMicrobiome from toddlers with high exuberance traits induced increased exploratory behaviour compared to vehicle-controls and rats receiving faeces from inhibited toddlers. Locomotor activity, social, and depressive-like behaviour remained unaffected. We noted a downregulation of the dopamine synapse pathway within the striatum of the rats that received faeces from the inhibited trait donors compared with vehicle-controls. Faecal microbiota of rats receiving faeces from the same donor resembled more each other than rats from a different cage. Clostridium species AM29 11AC in toddler microbiome was positively related to exuberance, but there were no cross-sectional associations between faecal metabolites in the human sample. ConclusionsFMT from exuberant toddlers lead to altered exploratory-related behaviour in rats.

microbiology↗

bioRxiv2018

Lower hemoglobin levels associate with lower body mass index and healthier metabolic profile

Hemoglobin (Hb) is the main carrier of oxygen. In general, high-end Hb levels within the normal range are considered beneficial for health1. However, activation of the hypoxia response has been shown to protect mice against metabolic dysfunction2-4. We used Hb levels as an indicator for oxygenation status and studied its association with >170 anthropometric and metabolic parameters in two Finnish birth cohorts both in cross-sectional and longitudinal design (max n = 7,175). Here we show a positive linear association between Hb levels and body mass index (BMI). Subjects with the lower Hb levels had better glucose tolerance, lower cholesterol and blood pressure levels, less adverse metabolite profiles and lower inflammatory load. Notably, these associations were not only mediated by the lower BMI, and the effect size of many of them increased with age. Polygenic risk score (PRS) analyses indicated shared genetic determinants between Hb levels and BMI, insulin, triglyceride and HDL cholesterol levels. Mendelian randomization (MR) analyses could not demonstrate causal relationships between Hb and metabolic parameters. However, manipulation of Hb levels by venesection in mice showed evidence for causal associations with body weight and metabolic parameters. Our findings suggest that lower-end normal Hb levels may be favorable for systemic metabolism involving mild chronic activation of the hypoxia response. Therefore modulation of Hb levels could be a novel strategy towards maintenance of metabolic health.

epidemiology↗