DNA methylation states in supercentenarians

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Molecular mechanisms associated with the strength of the anti-CMV response in nonagenarians

Infection with human cytomegalovirus (CMV) affects the function and composition of the immune system during ageing. In addition to the presence of the pathogen, the strength of the immune response, as measured by the anti-CMV IgG titre, has a significant effect on age-related pathogenesis. High anti-CMV IgG titres have been associated with increased mortality and functional impairment in the elderly. In this study, we were interested in identifying the molecular mechanisms that are associated with the strength of the anti-CMV response by examining the gene expression profiles that are associated with the level of the anti-CMV IgG titre. Results The level of the anti-CMV IgG titre is associated with the expression level of 663 transcripts in nonagenarians. These transcripts and their corresponding pathways are, for the most part, associated with metabolic functions, cell development and proliferation and other basic cellular functions. However, no prominent associations with the immune system were found, and no associated transcripts were found in young controls. Conclusions The lack of defence pathways associated with the strength of the anti-CMV response can indicate that the compromised immune system can no longer defend itself against the CMV infection. Our data imply that the association between high anti-CMV IgG titres and increased mortality and frailty is mediated by basic cellular processes.BioMed Central open acces

Sosiaaliturva työn murroksessa – palkkatyö, yrittäjyys ja toimeentulon riskit

Tämä raportti esittää, mitä haasteita työn murroksesta seuraa toimeentulon riskien, yrittäjäriskien ja sosiaaliturvan näkökulmasta, sekä miten näihin haasteisiin voitaisiin vastata. Yrittäjän ja palkansaajan sosiaaliturva laitetaan niin sanottuun triangeliin, jotta päästäisiin tarkastelemaan siirtymiä palkansaajasta yrittäjäksi, yrittäjyyden yhdistämistä palkkatyöhön ja sosiaaliturvan tarjoamaa suojaa näissä kohdin. Sosiaaliturvasta fokuksessa on erityisesti työttömyysturva, sillä sosiaaliturvaetuuksista siinä on eniten eroa yrittäjän ja palkansaajan välillä. Raportissa käydään läpi yrittäjyyden, palkkatyön ja sosiaaliturvan yhteensovittamista käsittelevää tutkimustietoa ja hallinnollisia dokumentteja, sekä tarkastellaan Iso-Britannian yleistukea (Universal Credit), Tanskan ja Ruotsin työmarkkinauudistuksia ja yrittäjien asemaa näissä uudistuksissa. Raportissa todetaan, että sosiaaliturvajärjestelmästä löytyviin ongelmiin, kuten komibityöläisten ja itsensätyöllistäjien ansiosidonnaiseen työttömyysturvaan, byrokratialoukkuihin ja itsensätyöllistäjien toisinaan heikkoihin mahdollisuuksiin vaikuttaa työnsä hinnoitteluun, pitäisi hakea ratkaisuja erilaisin kokeiluin, erilaiset tarpeet tunnistaen ja syntyvää tietoa systemaattisesti analysoiden. Työn murros lisää toimeentuloriskejä, minkä takia sosiaaliturvajärjestelmältä tarvitaan yksilöllistä tukea, joka suojaa sosiaalisilta riskeiltä mutta samaan aikaan sosiaaliturvan pitää edistää yritysten ja elinkeinojen uusiutumista. Raportti sisältää myös rahan, pääoman ja luovuuden käsitteiden uudelleenarvion ja hahmottelee tapoja, joilla nykyisiä käytäntöjä voitaisiin uudistaa uusien käsitteiden pohjalta niin, että ihmiset voisivat aiempaa täysipainoisemmin osallistua talouteen ja yhteiskuntaan

Biological aging of different blood cell types

Biological age (BA) captures detrimental age-related changes. The best-known and most-used BA indicators include DNA methylation–based epigenetic clocks and telomere length (TL). The most common biological sample material for epidemiological aging studies, whole blood, is composed of different cell types. We aimed to compare differences in BAs between blood cell types and assessed the BA indicators’ cell type-specific associations with chronological age (CA). An analysis of DNA methylation–based BA indicators, including TL, methylation level at cg16867657 in ELOVL2, as well as the Hannum, Horvath, DNAmPhenoAge, and DunedinPACE epigenetic clocks, was performed on 428 biological samples of 12 blood cell types. BA values were different in the majority of the pairwise comparisons between cell types, as well as in comparison to whole blood (p < 0.05). DNAmPhenoAge showed the largest cell type differences, up to 44.5 years and DNA methylation-based TL showed the lowest differences. T cells generally had the "youngest" BA values, with differences across subsets, whereas monocytes had the "oldest" values. All BA indicators, except DunedinPACE, strongly correlated with CA within a cell type. Some differences such as DNAmPhenoAge-difference between naïve CD4 + T cells and monocytes were constant regardless of the blood donor's CA (range 20–80 years), while for DunedinPACE they were not. In conclusion, DNA methylation–based indicators of BA exhibit cell type–specific characteristics. Our results have implications for understanding the molecular mechanisms underlying epigenetic clocks and underscore the importance of considering cell composition when utilizing them as indicators for the success of aging interventions.Peer reviewe

Aging-associated DNA methylation changes in middle-aged individuals: the Young Finns study

Background Chronological aging-associated changes in the human DNA methylome have been studied by multiple epigenome-wide association studies (EWASs). Certain CpG sites have been identified as aging-associated in multiple studies, and the majority of the sites identified in various studies show common features regarding location and direction of the methylation change. However, as a whole, the sets of aging-associated CpGs identified in different studies, even with similar tissues and age ranges, show only limited overlap. In this study, we further explore and characterize CpG sites that show close relationship between their DNA methylation level and chronological age during adulthood and which bear the relationship regardless of blood cell type heterogeneity. Results In this study, with a multivariable regression model adjusted for cell type heterogeneity, we identified 1202 aging-associated CpG sites (a-CpGs, FDR < 5 %), in whole blood in a population with an especially narrow age range (40 - 49 years). Repeatedly reported a-CpGs located in genes ELOVL2, FHL2, PENK and KLF14 were also identified. Regions with aging-associated hypermethylation were enriched regarding several gene ontology (GO) terms (especially in the cluster of developmental processes), whereas hypomethylated sites showed no enrichment. The genes with higher numbers of a-CpG hits were more often hypermethylated with advancing age. The comparison analysis revealed that of the 1202 a-CpGs identified in the present study, 987 were identified as differentially methylated also between nonagenarians and young adults in a previous study (The Vitality 90+ study), and importantly, the directions of changes were identical in the previous and in the present study. Conclusions Here we report that aging-associated DNA methylation features can be identified in a middle-aged population with an age range of only 9 years. A great majority of these sites have been previously reported as aging-associated in a population aged 19 to 90 years. Aging is associated with different types of changes in DNA methylation, clock-like as well as random. We speculate that the a-CpGs identified here in a population with a narrow age-range represent clock-like changes, as they showed concordant methylation behavior in population spanning whole adulthood as well.BioMed Central open acces

Frailty in Midlife as a Predictor of Changes in Body Composition from Midlife into Old Age : A Longitudinal Birth Cohort Study

Introduction: Few studies have investigated the association between frailty and subsequent body composition. Methods: We performed separate linear mixed model analyses to study the associations between changes in the participant frailty status assessed by a frailty index (FI) and subsequent body mass index (BMI), lean mass index (LMI), fat mass index (FMI), and FMI to LMI ratio values assessed on three occasions over 17 years. The analyses were carried out among 996 participants spanning from age 57 to 84 years. Results: With advancing age, LMI and BMI decreased, whereas FMI and FMI to LMI ratio increased. Participants with "stable frailty,"followed by those with "increasing frailty"experienced faster decreases in LMI and faster increases in FMI and FMI to LMI ratio values from midlife into old age relative to those in the group "stable not frail."Contrastingly, those in the highest third of absolute annual increase in FMI and FMI to LMI ratio became more frail faster from midlife into old age relative to those in the lowest third. Conclusions: We found evidence of an adverse health outcome of frailty where lean indices declined faster and fat indices and fat-to-lean ratios increased faster from midlife into old age. The changes resembled those that occurred with aging, but at a faster pace. The relationship between body composition and frailty is likely bidirectional, where high or increasing levels of fat are associated with the risk of becoming more frail earlier, but where a longer duration of frailty may increase the risk of faster age-related changes to body composition.Peer reviewe

Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals

BioMed Central open acces

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

Aims & methods: The aim of this study was to characterize the methylation level of a polymorphically imprinted gene, VTRNA2-1/nc886, in human populations and somatic tissues.48 datasets, consisting of more than 30 tissues and >30,000 individuals, were used. Results: nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, whereas similar to 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. Conclusion: The nc886 imprint may be established in the oocyte, and, after implantation, the methylation status is stable, excluding a few specific tissues. Tweetable abstract Methylation status of a polymorphically imprinted gene, VTRNA2-1/nc886, is stable in human populations (48 cohorts, n > 30,000) and in somatic tissues, except in cerebellum and skeletal muscle. Twin data suggest it may already be established in the oocyte.Peer reviewe

Leukocyte Telomere Length in the Finnish Diabetes Prevention Study

Peer reviewe