Biology subjects

Marttila, S.

Publications and source records attributed to Marttila, S..

7 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↗

bioRxiv2026

Traditional disease risk factors outperform epigenetic clocks as predictors of non-communicable disease morbidity in a middle-aged cohort

DNA methylation-based epigenetic clocks have been highlighted as promising biomarkers of ageing, and they have been shown to robustly predict morbidity and mortality. However, current literature is lacking a formal analysis of the increased prediction accuracy, or the added value, of the epigenetic clocks over traditional risk factors of common chronic diseases. Here, we have compared the most commonly used epigenetic clocks and traditional risk factors as predictors of incidence of ageing-associated non-communicable chronic disease in a 7-to-9-year follow-up in a middle-aged population cohort (n=1108, aged 34 to 49 years at baseline). In our cohort, a statistical model consisting of a combination of traditional risk factors outperforms any model including an epigenetic clock. The added value of epigenetic clock measurements over simple and affordable traditional risk factors should be clearly established, if epigenetic clocks are to be used in clinical settings or as tools of personal health monitoring.

molecular biology↗

bioRxiv2024

Biological aging of different blood cell types

A biological age (BA) indicator is intended to capture detrimental age-related changes occurring with passing time. To date, the best-known and used BA indicators include DNA-methylation-based epigenetic ages (epigenetic clocks) and telomere length. The most common biological sample material for epidemiological aging studies is composed of different cell types, whole blood. We aimed to compare differences in BAs between blood cell types and assessed BA indicators cell type-specific associations with donors calendar age. Analysis on DNA methylation-based BA indicators including telomere length, methylation level at cg16867657 (a CpG-site in ELOVL2) and the Hannum, Horvath, DNAmPhenoAge and DunedinPACE epigenetic clocks was performed in 428 biological samples from 12 blood cell types. BA values were different (p<0.05) in the majority of pairwise comparisons between the cell types. Most cell types also displayed differences as compared to whole blood (p<0.05). Some of the observed differences persisted across blood donors calendar ages from 20 to 80 years (50-years-difference in DNAmPhenoAge between naive CD4+ T cells and monocytes), while others did not (up to four-fold difference in DunedinPACE values between monocytes and B cells). All BA indicators, except DunedinPACE, had mostly a very strong correlation with donors calendar age within a cell type. Our findings demonstrate that DNA methylation-based indicators of biological age exhibit cell type-specific characteristics, underscoring the importance of accounting for cell composition in related studies. Our results have implications for understanding the molecular mechanisms underlying epigenetic clocks and and provide guidance for utilizing them as indicators for success of aging interventions.

molecular biology↗

bioRxiv2024

Histological analysis of Scots pine (Pinus sylvestris L.) seedlings in response to root rot pathogen Heterobasidion annosum inoculation

Heterobasidion root rot is one of the most serious and economically destructive forest diseases in the Northern Hemisphere. Although several studies have explored the genetic and chemical responses of Scots pine to Heterobasidion spp. infection, the histological defense responses of this species remain poorly understood. In this study, we investigated the histological responses of three-year-old Scots pine seedlings to Heterobasidion annosum inoculation and a wounding treatment with no inoculation, focusing on lesion length and traumatic resin-duct characteristics (density, size). Our results showed that H. annosum-inoculated seedlings exhibited significantly more browning necrotic lesions than wounded seedlings. Traumatic resin duct density was significantly higher in H. annosum-inoculated seedlings compared to wounded seedlings, particularly within the first two cm from the inoculation point. However, as the distance from the inoculation point increased, the resin duct density decreased. Notably, there were neither statistically significant differences in the mean size of traumatic and constitutive resin ducts between the two treatments, nor within the H. annosum inoculation treatment itself. In contrast, within the wound treatment, the mean size of traumatic resin ducts was found to be significantly smaller than that of constitutive resin ducts. Furthermore, traumatic resin ducts did not prove to be reliable markers for dating H. annosum infection in Scots pine. Overall, this study advances knowledge about Scots pines histological defense mechanisms against H. annosum invasion, which has significant implications.

pathology↗

bioRxiv2023

Non-coding 886 (nc886/vtRNA2-1), the epigenetic odd duck - implications for future studies

Non-coding 886 (nc886, VTRNA2-1) is the only human polymorphically imprinted gene, in which the methylation status is not determined by genetics. Existing literature regarding the establishment, stability, and consequences of the methylation pattern, as well as the nature and function of the nc886 RNAs transcribed from the locus, are contradictory. For example, the methylation status of the locus has been reported to be stable through life and across somatic tissues, but also susceptible to environmental effects. The nature of the produced nc886 RNAs has been redefined multiple times and are still under debate and in carcinogenesis, these RNAs have been reported to have conflicting roles. In addition, due to the bimodal methylation pattern of the nc886 locus, traditional genome-wide methylation analyses can lead to false-positive results, especially in smaller datasets. Here, we aim to summarise the existing literature regarding nc886, discuss how the characteristics of nc886 give rise to contradictory results, and reinterpret, reanalyse and, where possible, replicate the results presented in the current literature. We also introduce novel findings on how the nc886 methylation pattern distribution is associated with the geographical origins of the population and describe the methylation changes in a large variety of human tumours. Through the example of this one peculiar genetic locus and RNA, we aim to highlight issues in the analysis of DNA methylation and non-coding RNAs in general and offer our suggestions for what should be taken into consideration in future analyses.

molecular biology↗

bioRxiv2022

Methylation status of VTRNA2-1/nc886 is stable across human populations, monozygotic twin pairs and in majority of somatic tissues

Aims and methodsOur aim was to characterise the methylation level of a polymorphically imprinted gene, VTRNA2-1/nc886, in human populations and somatic tissues. We utilised 48 datasets, consisting of >30 different tissues and >30 000 individuals. ResultsWe show that the nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, while [~]30% of dizygotic twin pairs present discordant methylation in the nc886 locus. The methylation levels of nc886 are uniform across somatic tissues, except in cerebellum and skeletal muscle. ConclusionWe hypothesize that the nc886 imprint is established in the oocyte and that after implantation, the methylation status is stable, excluding a few specific tissues.

molecular biology↗

bioRxiv2021

Methylation pattern of nc886 in non-human mammals

BackgroundIn humans, the nc886 locus is a polymorphically imprinted metastable epiallele. Periconceptional conditions have an effect on the methylation status of nc886, and further, this methylation status is associated with health outcomes in later life, in line with the Developmental Origins of Health and Disease (DOHaD) hypothesis. Animal models would offer opportunities to study the associations between periconceptional conditions, nc886 methylation status and metabolic phenotypes further. Thus, we set out to investigate the methylation pattern of the nc886 locus in non-human mammals. DataWe obtained DNA methylation data from the data repository GEO for mammals, whose nc886 gene included all three major parts of nc886 and had sequency similarity of over 80% with the human nc886. Our final sample set consisted of DNA methylation data from humans, chimpanzees, bonobos, gorillas, orangutangs, baboons, macaques, vervets, marmosets and guinea pigs. ResultsIn human data sets the methylation pattern of nc886 locus followed the expected bimodal distribution, indicative of polymorphic imprinting. In great apes, we identified a unimodal DNA methylation pattern with 50% methylation level in all individuals and in all subspecies. In Old World monkeys, the between individual variation was greater and methylation on average was close to 60%. In guinea pigs the region around the nc886 homologue was non-methylated. Results obtained from the sequence comparison of the CTCF binding sites flanking the nc886 gene support the results on the DNA methylation data. ConclusionsOur results indicate that unlike in humans, nc886 is not a polymorphically imprinted metastable epiallele in non-human primates or in guinea pigs, thus implying that animal models are not applicable for nc886 research. The obtained data suggests that the nc886 region may be classically imprinted in great apes, and potentially also in Old World monkeys, but not in guinea pigs.

molecular biology↗