Inflamm-aging of the stem cell niche: Breast cancer as a paradigmatic example: Breakdown of the multi-shell cytokine network fuels cancer in aged people.

Inflamm-aging is a relatively new terminology used to describe the age-related increase in the systemic pro-inflammatory status of humans. Here, we represent inflamm-aging as a breakdown in the multi-shell cytokine network, in which stem cells and stromal fibroblasts (referred to as the stem cell niche) become pro-inflammatory cytokine over-expressing cells due to the accumulation of DNA damage. Inflamm-aging self-propagates owing to the capability of pro-inflammatory cytokines to ignite the DNA-damage response in other cells surrounding DNA-damaged cells. Macrophages, the major cellular player in inflamm-aging, amplify the phenomenon, by broadcasting pro-inflammatory signals at both local and systemic levels. On the basis of this, we propose that inflamm-aging is a major contributor to the increase in cancer incidence and progression in aged people. Breast cancer will be presented as a paradigmatic example for this relationship

Recent results from the Arctic Radiation and Turbulence Interaction STudy (ARTIST) project

Ground-based measurements were conducted at Ny-˚Alesund in the Svalbard Islands in the framework of the research project ARTIST (Arctic Radiation and Turbulence Interaction STudy) funded by the European Communities. Key objectivesof the campaign were: 1) provide all participantswith ground reference data as input to models describing the development of the atmospheric boundary level, 2) compute the surface roughness length in order to characterise the surface of the site, 3) parameterise the surface energy exchanges, calculating the surface radiation flux, the sensible and latent heat fluxes, and 4) obtain the surface energy balance during both clear and cloudy sky conditions. The cloud radiative forcing has been also estimated. Final results of the analysis of the data set are presented

A polymorphic variant of the insulin-like growth factor 1 (IGF-1) receptor correlates with male longevity in the Italian population: a genetic study and evaluation of circulating IGF-1 from the "Treviso Longeva (TRELONG)" study

<p>Abstract</p> <p>Background</p> <p>An attenuation of the insulin-like growth factor 1 (IGF-1) signaling has been associated with elongation of the lifespan in simple metazoan organisms and in rodents. In humans, IGF-1 level has an age-related modulation with a lower concentration in the elderly, depending on hormonal and genetic factors affecting the IGF-1 receptor gene (<it>IGF-1R</it>).</p> <p>Methods</p> <p>In an elderly population from North-eastern Italy (<it>n </it>= 668 subjects, age range 70–106 years) we investigated the <it>IGF-1R </it>polymorphism G3174A (<it>rs2229765</it>) and the plasma concentration of free IGF-1. Frequency distributions were compared using χ²-test "Goodness of Fit" test, and means were compared by one-way analysis of variance (ANOVA); multiple regression analysis was performed using JMP7 for SAS software (SAS Institute, USA). The limit of significance for genetic and biochemical comparison was set at α = 0.05.</p> <p>Results</p> <p>Males showed an age-related increase in the A-allele of <it>rs2229765 </it>and a change in the plasma level of IGF-1, which dropped significantly after 85 years of age (85+ group). In the male 85+ group, A/A homozygous subjects had the lowest plasma IGF-1 level. We found no clear correlation between <it>rs2229765 </it>genotype and IGF-1 in the females.</p> <p>Conclusion</p> <p>These findings confirm the importance of the <it>rs2229765 </it>minor allele as a genetic predisposing factor for longevity in Italy where a sex-specific pattern for IGF-1 attenuation with ageing was found.</p

Enhanced engraftment and repairing ability of human adipose-derived stem cells, conveyed by pharmacologically active microcarriers continuously releasing HGF and IGF-1, in healing myocardial infarction in rats

One of the main cause of ineffective cell therapy in repairing the damaged heart is the poor yield of grafted cells. To overcome this drawback, rats with 4-week-old myocardial infarction (MI) were injected in the border zone with human adipose-derived stem cells (ADSCs) conveyed by poly(lactic-co-glycolic acid) microcarriers (PAMs) releasing hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) (GFsPAMs). According to treatments, animals were subdivided into different groups: MI_ADSC, MI_ADSC/PAM, MI_GFsPAM, MI_ADSC/GFsPAM, and untreated MI_V. Two weeks after injection, a 31% increase in ADSC engraftment was observed in MI_ADSC/PAM compared with MI_ADSC (p &lt; 0.05). A further ADSC retention was obtained in MI_ADSC/GFsPAM with respect to MI_ADSC (106%, p &lt; 0.05) and MI_ADSC/PAM (57%, p &lt; 0.05). A 130% higher density of blood vessels of medium size was present in MI_ADSC/GFsPAM compared with MI_ADSC (p &lt; 0.01). MI_ADSC/GFsPAM also improved, albeit slightly, left ventricular remodeling and hemodynamics with respect to the other groups. Notably, ADSCs and/or PAMs, with or without HGF/IGF-1, trended to induce arrhythmias in electrically driven, Langendorff-perfused, hearts of all groups. Thus, PAMs releasing HGF/IGF-1 markedly increase ADSC engraftment 2 weeks after injection and stimulate healing in chronically infarcted myocardium, but attention should be paid to potentially negative electrophysiological consequences

A meta-analysis of genome-wide association studies of epigenetic age acceleration

Funding: Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). Genotyping and DNA methylation profiling of the GS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” ((STRADL) Reference 104036/Z/14/Z)). Funding details for the cohorts included in the study by Lu et al. (2018) can be found in their publication. HCW is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh and by an ESAT College Fellowship from the University of Edinburgh. AMM & HCW acknowledge the support of the Dr. Mortimer and Theresa Sackler Foundation. SH acknowledges support from grant 1U01AG060908-01. REM is supported by Alzheimer’s Research UK major project grant ARUK-PG2017B-10. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability: Summary statistics from the research reported in the manuscript will be made available immediately following publication on the Edinburgh Data Share portal with a permanent digital object identifier (DOI). According to the terms of consent for Generation Scotland participants, requests for access to the individual-level data must be reviewed by the GS Access Committee ([email protected]). Individual-level data are not immediately available, due to confidentiality considerations and our legal obligation to protect personal information. These data will, however, be made available upon request and after review by the GS access committee, once ethical and data governance concerns regarding personal data have been addressed by the receiving institution through a Data Transfer Agreement.Peer reviewedPublisher PD