Maria Antonietta Stazi

Health status and 6 years survival of 552 90+ Italian sib-ships recruited within the EU Project GEHA (GEnetics of Healthy Ageing)

In a scenario of increasing life expectancy worldwide, it is mandatory to identify the characteristics of a healthy aging phenotype, including survival predictors, and to disentangle those related to environment/lifestyle versus those related to familiarity/genetics. To this aim we comprehensively characterised a cohort of 1,160 Italian subjects of 90xa0years and over (90+, mean age 93xa0years; age range 90–106xa0years) followed for 6xa0years survival, belonging to 552 sib-ships (familiar longevity) recruited (2005–2008) within the EU-funded GEHA project in three Italian geographic areas (Northern, Central and Southern Italy) different for urban/rural and socio-economical characteristics. On the whole, the following factors emerged as significant predictors of survival after 90xa0years of age: absence of cognitive impairment and physical disability, high hand grip strength scores and body mass index (BMI) values, “excellent/good” self-reported health, high haemoglobin and total cholesterol levels and low creatinine levels. These parameters, excluding BMI values, were also significantly associated within sib-ships, suggesting a strong familial/genetic component. Geographical micro-heterogeneity of survival predictors emerged, such as functional and physical status being more important in Southern than in Central and Northern Italy. In conclusion, we identified modifiable survival predictors related to specific domains, whose role and importance vary according to the geographic area considered and which can help in interpreting the genetic results obtained by the GEHA project, whose major aim is the comprehensive evaluation of phenotypic and genetic data.

Serum transforming growth factor β1 during diabetes development in non-obese diabetic mice and humans

Recent data show that regulatory cells with transforming growth factor (TGF)‐β1‐dependent activity are able to restore self‐tolerance in overtly diabetic non‐obese diabetic (NOD) mice. Thus, TGF‐β1 seems to have a relevant role in protection from autoimmune diabetes. Our aim was to investigate the possible significance of serum TGF‐β1 measurement in the natural history of diabetes in NOD mice, as well as in children positive for at least one islet‐related antibody. Serum TGF‐β1 (both total and active) was measured by enzyme‐linked immunosorbent assay at monthly intervals in 26 NOD mice during the spontaneous development of diabetes and, on a yearly basis, in nine siblings of patients with type 1 diabetes (T1D) with a follow‐up of 4 years. Diabetes appeared between the 12th week of age and the end of the study period (36 weeks) in 17 mice. TGF‐β1 serum level variations occurred in the prediabetic period in both NOD mice and humans and diabetes diagnosis followed a continuing reduction of active TGF‐β1 (aTGF‐β1) serum levels. In mice, aTGF‐β1 serum levels measured at 4 weeks of age correlated positively with severity of insulitis, and negatively with percentage of insulin‐positive cells. Our findings suggest that in NOD mice serum TGF‐β1 levels during the natural history of the diabetes reflect the course of islet inflammation. The measurement of aTGF‐β1 in islet‐related antibody‐positive subjects may provide insights into the natural history of prediabetic phase of T1D.