The biological basis of the aging process

El procés biològic bàsic subjacent de l’envelliment va ésser avançat per la teoria de l’envelliment basada en els radicals lliures l’any 1954: la reacció dels radicals lliures actius, produïts fisiològicament en l’organisme, amb els constituents cel·lulars inicia els canvis associats a l’envelliment. La implicació dels radicals lliures en l’envelliment està relacionada amb el seu paper clau en l’origen i l’evolució de la vida. La informació disponible avui en dia ens mostra que la composició específica de les macromolècules cel·lulars (proteïnes, àcids nucleics, lípids i carbohidrats) en les espècies animals longeves tenen intrínsicament una resistència elevada a la modificació oxidativa, la qual cosa probablement contribueix a la longevitat superior d’aquestes espècies. Les espècies longeves també mostren unes taxes reduïdes de producció de radicals lliures i de lesió oxidativa. D’altra banda, la restricció dietària disminueix la producció de radicals lliures i la lesió molecular oxidativa. Aquests canvis estan directament associats a la reducció de la ingesta de proteïnes dels animals sotmesos a restricció, que alhora sembla que són deguts específicament a la reducció de la ingesta de metionina. En aquesta revisió s’emfatitza que una taxa baixa de generació de lesió endògena i una resistència intrínsecament elevada a la modificació de les macromolècules cel·lulars són trets clau de la longevitat de les espècies animals.

First trimester maternal level of PAPP-A, βhCG and ethnicity as predictive of Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is one of the leading causes of perinatal mortality and morbidity. Nowadays, this condition is detected in the 3rt and last trimester of gestation when the pathology is already established and success of therapeutic strategies are limited. As the physiopathology of the disease suggests that the problem stems from poor placental implantation, it would be quite advantageous to identify women at increased risk in the first or second trimester of gestation because it then might be possible to offer treatment interventions or at least to establish increased surveillance for high risk pregnancies. Maternal levels of pregnancy-associated plasma protein-A (PAPP-A) and free β human chorionic gonadotropin (free βhCG) has been shown to be effective in first trimester screening for chromosomal abnormalities, primarily trisomies 21, 13 and 18. Previous studies evaluating PAPP-A and free βhCG measured in the first trimester in relation with IUGR have provided conflicting results. Moreover, it has been suggested that black ethnicity is another important predictive factor for fetal growth restriction.Objective: To analyse the association between first trimester serum analytes (PAPP-A and free βhCG) and ethnicity with Intrauterine Growth Restriction.Methods: The study consists in a retrospective cohort, including all singleton pregnancies with complete outcome data that had undergone first trimester screening (PAPP-A and free βhCG) at 11-13+6weeks of gestation between 1/1/2010 - 31/12/2012 in Hospital Universitari Dr Josep Trueta. Biochemical markers are converted to multiples of the median (MoMs) and percentiles 5 and 10 are calculated. The association between free βhCG and PAPP-A with the incidence of IUGR is evaluated in combination with maternal ethnicity. Bivariate and logistic regression analyses are performed to adjust this association for co variables

First trimester maternal level of PAPP-A, βhCG and ethnicity as predictive of Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is one of the leading causes of perinatal mortality and morbidity. Nowadays, this condition is detected in the 3rt and last trimester of gestation when the pathology is already established and success of therapeutic strategies are limited. As the physiopathology of the disease suggests that the problem stems from poor placental implantation, it would be quite advantageous to identify women at increased risk in the first or second trimester of gestation because it then might be possible to offer treatment interventions or at least to establish increased surveillance for high risk pregnancies. Maternal levels of pregnancy-associated plasma protein-A (PAPP-A) and free β human chorionic gonadotropin (free βhCG) has been shown to be effective in first trimester screening for chromosomal abnormalities, primarily trisomies 21, 13 and 18. Previous studies evaluating PAPP-A and free βhCG measured in the first trimester in relation with IUGR have provided conflicting results. Moreover, it has been suggested that black ethnicity is another important predictive factor for fetal growth restriction.Objective: To analyse the association between first trimester serum analytes (PAPP-A and free βhCG) and ethnicity with Intrauterine Growth Restriction.Methods: The study consists in a retrospective cohort, including all singleton pregnancies with complete outcome data that had undergone first trimester screening (PAPP-A and free βhCG) at 11-13+6weeks of gestation between 1/1/2010 - 31/12/2012 in Hospital Universitari Dr Josep Trueta. Biochemical markers are converted to multiples of the median (MoMs) and percentiles 5 and 10 are calculated. The association between free βhCG and PAPP-A with the incidence of IUGR is evaluated in combination with maternal ethnicity. Bivariate and logistic regression analyses are performed to adjust this association for co variables

First trimester maternal level of PAPP-A, βhCG and ethnicity as predictive of Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is one of the leading causes of perinatal mortality and morbidity. Nowadays, this condition is detected in the 3rt and last trimester of gestation when the pathology is already established and success of therapeutic strategies are limited. As the physiopathology of the disease suggests that the problem stems from poor placental implantation, it would be quite advantageous to identify women at increased risk in the first or second trimester of gestation because it then might be possible to offer treatment interventions or at least to establish increased surveillance for high risk pregnancies. Maternal levels of pregnancy-associated plasma protein-A (PAPP-A) and free β human chorionic gonadotropin (free βhCG) has been shown to be effective in first trimester screening for chromosomal abnormalities, primarily trisomies 21, 13 and 18. Previous studies evaluating PAPP-A and free βhCG measured in the first trimester in relation with IUGR have provided conflicting results. Moreover, it has been suggested that black ethnicity is another important predictive factor for fetal growth restriction.Objective: To analyse the association between first trimester serum analytes (PAPP-A and free βhCG) and ethnicity with Intrauterine Growth Restriction.Methods: The study consists in a retrospective cohort, including all singleton pregnancies with complete outcome data that had undergone first trimester screening (PAPP-A and free βhCG) at 11-13+6weeks of gestation between 1/1/2010 - 31/12/2012 in Hospital Universitari Dr Josep Trueta. Biochemical markers are converted to multiples of the median (MoMs) and percentiles 5 and 10 are calculated. The association between free βhCG and PAPP-A with the incidence of IUGR is evaluated in combination with maternal ethnicity. Bivariate and logistic regression analyses are performed to adjust this association for co variables

Lifespan extension by calorie restriction relies on the Sty1 MAP kinase stress pathway

Either calorie restriction, loss of function of the nutrient-dependent PKA or TOR/SCH9 pathways, or activation of stress defences improves longevity in different eukaryotes. However, the molecular links between glucose depletion, nutrient-dependent pathways and stress responses are unknown. Here we show that either calorie restriction or inactivation of nutrient-dependent pathways induces life-span extension in fission yeast, and that such effect is dependent on the activation of the stress-dependent Sty1 MAP kinase. During transition to stationary phase in glucose-limiting conditions, Sty1 becomes activated and triggers a transcriptional stress program, whereas such activation does not occur under glucose-rich conditions. Deletion of the genes coding for the SCH9-homologue Sck2 or the Pka1 kinases, or mutations leading to constitutive activation of the Sty1 stress pathway increase life span under glucose-rich conditions, and importantly such beneficial effects depend ultimately on Sty1. Furthermore, cells lacking Pka1 display enhanced oxygen consumption and Sty1 activation under glucose-rich conditions. We conclude that calorie restriction favours oxidative metabolism, reactive oxygen species production and Sty1 MAP kinase activation, and this stress pathway favours life-span extension.