Sairauksien ja addiktioiden "logiikasta"

Summary: The "logic" of diseases and addictions

Identification of a prognostic signature for old-age mortality by integrating genome-wide transcriptomic data with the conventional predictors: the Vitality 90+ Study

Background Prediction models for old-age mortality have generally relied upon conventional markers such as plasma-based factors and biophysiological characteristics. However, it is unknown whether the existing markers are able to provide the most relevant information in terms of old-age survival or whether predictions could be improved through the integration of whole-genome expression profiles. Methods We assessed the predictive abilities of survival models containing only conventional markers, only gene expression data or both types of data together in a Vitality 90+ study cohort consisting of n = 151 nonagenarians. The all-cause death rate was 32.5% (49 of 151 individuals), and the median follow-up time was 2.55 years. Results Three different feature selection models, the penalized Lasso and Ridge regressions and the C-index boosting algorithm, were used to test the genomic data. The Ridge regression model incorporating both the conventional markers and transcripts outperformed the other models. The multivariate Cox regression model was used to adjust for the conventional mortality prediction markers, i.e., the body mass index, frailty index and cell-free DNA level, revealing that 331 transcripts were independently associated with survival. The final mortality-predicting transcriptomic signature derived from the Ridge regression model was mapped to a network that identified nuclear factor kappa beta (NF-κB) as a central node. Conclusions Together with the loss of physiological reserves, the transcriptomic predictors centered around NF-κB underscored the role of immunoinflammatory signaling, the control of the DNA damage response and cell cycle, and mitochondrial functions as the key determinants of old-age mortality.BioMed Central open acces

Aging-associated increase in indoleamine 2,3-dioxygenase (IDO) activity appears to be unrelated to the transcription of the IDO1 or IDO2 genes in peripheral blood mononuclear cells

<p>Abstract</p> <p>Background</p> <p>Old age is associated with increased levels of circulating pro-inflammatory cytokines, a phenomenon termed inflamm-aging. Elevated levels of pro-inflammatory cytokines have been associated with several age-associated diseases and with a shortened lifespan. Indoleamine 2,3-dioxygenase (IDO) has immunomodulatory properties and its activity is elevated in inflammation, autoimmune disorders and malignancies. We have previously shown that IDO activity is increased in nonagenarians compared to young individuals and that high IDO activity is associated with mortality at old age.</p> <p>Findings</p> <p>In this study our aim was to assess whether this difference in IDO activity in the plasma was due to the differential expression of either the IDO1 or IDO2 gene in peripheral blood mononuclear cells. Our results show that IDO1 and IDO2 are not differently expressed in nonagenarians compared to controls and that the expression of IDO genes is not associated with the level of IDO activity in the plasma.</p> <p>Conclusion</p> <p>The level of IDO activity in the plasma is not regulated through the expression of IDO1 or IDO2 in the peripheral blood mononuclear cells.</p

Is There Successful Aging for Nonagenarians? The Vitality 90+ Study

Objectives. This study was designed (1) to estimate the prevalence of successful aging among nonagenarians based on six different models and (2) to investigate whether successful aging is associated with socio-demographic factors. Methods. A mailed survey was conducted with people aged 90+ in Tampere in 2010. Responses were received from 1283 people. The prevalence of successful aging was measured by six multidimensional models including physical, social, and psychological components. Age, sex, marital status, level of education, and place of living were studied as factors associated with successful aging. Results. The prevalence of successful aging varied from 1.6% to 18.3% depending on the model applied. Successful aging was more prevalent in men, and also more prevalent among community-living people. In most models, successful aging was also associated with younger age, being married, and a higher level of education. Discussion. Models which emphasize the absence of disease and activity as criteria for successful aging may not be the most relevant and applicable in oldest old. Instead, preference should be given to models that focus more on autonomy, adaptation and sense of purpose. Age-sensitive approaches would help us better understand the potential of successful aging among individuals who already have success in longevity

Prior myocardial infarction, coronary artery disease extent, diabetes mellitus, and CERT2 score for risk stratification in stable coronary artery disease

Peer reviewe

Ilmastonmuutos pääkaupunkiseudulla

Ilmasto on jo muuttunut ihmiskunnan kasvihuonekaasupäästöjen seurauksena. Ilmastomalleihin perustuvien arvioiden mukaan lämpeneminen jatkuu ja sen suuruus ja vaikutukset riippuvat päästöjen määrän kehityksestä eli niiden rajoittamisen tehokkuudesta. Koska ilmakehään jo tähän mennessä päässeet kasvihuonekaasupäästöt vaikuttavat siellä vielä vuosikymmeniä, muuttuviin olosuhteisiin varautuminen esimerkiksi kaupungeissa on joka tapauksessa välttämätöntä. Tuoreimpien arvioiden mukaan pääkaupunkiseudun ilmasto lämpenee kaikkina vuodenaikoina, talvella enemmän kuin kesällä. Mikäli päästöjen hillinnässä onnistutaan tyydyttävästi, vuoteen 2100 mennessä tammikuun keskilämpötila on arvioiden mukaan reilut 5°C korkeampi kuin nykyään, ja vastaavasti heinäkuussa ero on noin 3°C. Äärimmäisen alhaiset lämpötilat harvinaistuvat voimakkaasti. Vuorokauden korkeimmat lämpötilat kesäisin kohoavat samaa tahtia keskilämpötilan kohoamisen kanssa. Talvella sataa selvästi nykyistä enemmän ja aurinkoa nähdään harvemmin. Keskimääräiset ja suurimmat sademäärät sekä sadepäivien määrä kasvavat. Kesällä rankkasateiden arvioidaan voimistuvan runsaat 10 % sadassa vuodessa. 1900-luvun loppuvuosikymmeninä noin kerran 20 vuodessa havaittu rankkasade koetaan 2000-luvun lopulla hiukan useammin kuin kerran kymmenessä vuodessa, ja kerran sadassa vuodessa esiintynyt rankkasade noin kerran 30 vuodessa. Keskimääräiset tuulen voimakkuudet pysyvät likimain ennallaan. Merenpinnan keskimääräinen korkeus Helsingin edustalla noussee muutamia kymmeniä senttimetrejä. Merellä jäät keskimäärin ohenevat ja jään pinta-ala pienentyy. Kuitenkin yksittäisiä runsasjäisiäkin talvia esiintyy vielä lähivuosikymmeninä. Vaikka ilmastonmuutoksen vaikutuksista osan voidaan ajatella olevan Suomessa suotuisia (lämmitystarpeen pieneneminen, pidempi kasvukausi), maailmanlaajuisesti suurin osa vaikutuksista on ihmiskunnan ja maapallon eliöstön kannalta erittäin epäsuotuisia (entistä voimakkaammat äärisääilmiöt, kuivuus, nälänhätä, pakolaisuus). Koska päästöt eivät tunne valtakuntien rajoja, päästöjen hillinnästä on sovittava kansainvälisesti. Kansainvälisistä sopimuksista tuorein on Pariisin ilmastosopimus vuodelta 2015, jota tarkastellaan myös lyhyesti tässä raportissa. Tähän raporttiin on koostettu viimeisin tieto ilmastonmuutoksen vaikutuksista pääkaupunkiseudulla perustuen IPCC:n 5. arviointiraportin RCP-kasvihuone-kaasupäästöskenaarioihin. Raportti siten päivittää aiempia pääkaupunki-seudulle tehtyjä vastaavia arviointeja

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