Does oxidative stress shorten telomeres in vivo? A review

The length of telomeres, the protective caps of chromosomes, is increasingly used as a biomarker of individual health state because it has been shown to predict chances of survival in a range of endothermic species including humans. Oxidative stress is presumed to be a major cause of telomere shortening, but most evidence to date comes from in vitro cultured cells. The importance of oxidative stress as a determinant of telomere shortening in vivo remains less clear and has recently been questioned. We, therefore, reviewed correlative and experimental studies investigating the links between oxidative stress and telomere shortening in vivo. While correlative studies provide equivocal support for a connection between oxidative stress and telomere attrition (10 of 18 studies), most experimental studies published so far (seven of eight studies) partially or fully support this hypothesis. Yet, this link seems to be tissue-dependent in some cases, or restricted to particular categories of individual (e.g. sex-dependent) in other cases. More experimental studies, especially those decreasing antioxidant protection or increasing pro-oxidant generation, are required to further our understanding of the importance of oxidative stress in determining telomere length in vivo. Studies comparing growing versus adult individuals, or proliferative versus non-proliferative tissues would provide particularly important insights

A marker of biological ageing predicts adult risk preference in European starlings, Sturnus vulgaris

Why are some individuals more prone to gamble than others? Animals often show preferences between 2 foraging options with the same mean reward but different degrees of variability in the reward, and such risk preferences vary between individuals. Previous attempts to explain variation in risk preference have focused on energy budgets, but with limited empirical support. Here, we consider whether biological ageing, which affects mortality and residual reproductive value, predicts risk preference. We studied a cohort of European starlings (Sturnus vulgaris) in which we had previously measured developmental erythrocyte telomere attrition, an established integrative biomarker of biological ageing. We measured the adult birds’ preferences when choosing between a fixed amount of food and a variable amount with an equal mean. After controlling for change in body weight during the experiment (a proxy for energy budget), we found that birds that had undergone greater developmental telomere attrition were more risk averse as adults than were those whose telomeres had shortened less as nestlings. Developmental telomere attrition was a better predictor of adult risk preference than either juvenile telomere length or early-life food supply and begging effort. Our longitudinal study thus demonstrates that biological ageing, as measured via developmental telomere attrition, is an important source of lasting differences in adult risk preferences

Early-life adversity accelerates cellular ageing and affects adult inflammation: experimental evidence from the European starling

Early-life adversity is associated with accelerated cellular ageing during development and increased inflammation during adulthood. However, human studies can only establish correlation, not causation, and existing experimental animal approaches alter multiple components of early-life adversity simultaneously. We developed a novel hand-rearing paradigm in European starling nestlings (Sturnus vulgaris), in which we separately manipulated nutritional shortfall and begging effort for a period of 10 days. The experimental treatments accelerated erythrocyte telomere attrition and increased DNA damage measured in the juvenile period. For telomere attrition, amount of food and begging effort exerted additive effects. Only the combination of low food amount and high begging effort increased DNA damage. We then measured two markers of inflammation, high-sensitivity C-reactive protein and interleukin-6, when the birds were adults. The experimental treatments affected both inflammatory markers, though the patterns were complex and different for each marker. The effect of the experimental treatments on adult interleukin-6 was partially mediated by increased juvenile DNA damage. Our results show that both nutritional input and begging effort in the nestling period affect cellular ageing and adult inflammation in the starling. However, the pattern of effects is different for different biomarkers measured at different time points

FACS purification and transcriptome analysis of drosophila neural stem cells reveals a role for Klumpfuss in self-renewal

Drosophila neuroblasts (NBs) have emerged as a model for stem cell biology that is ideal for genetic analysis but is limited by the lack of cell-type-specific gene expression data. Here, we describe a method for isolating large numbers of pure NBs and differentiating neurons that retain both cell-cycle and lineage characteristics. We determine transcriptional profiles by mRNA sequencing and identify 28 predicted NB-specific transcription factors that can be arranged in a network containing hubs for Notch signaling, growth control, and chromatin regulation. Overexpression and RNA interference for these factors identify Klumpfuss as a regulator of self-renewal. We show that loss of Klumpfuss function causes premature differentiation and that overexpression results in the formation of transplantable brain tumors. Our data represent a valuable resource for investigating Drosophila developmental neurobiology, and the described method can be applied to other invertebrate stem cell lineages as well

Aging trajectories are trait- and sex-specific in the long-lived Alpine swift

Senescence is defined as the general deterioration of the organism (i.e. physiology, morphology, reproduction), and is associated with increasing mortality and decreasing fertility with age. Although senescence has now been widely reported in wild animals, little is known on whether senescence affects all traits, whether this process is synchronized across traits, and whether males and females are affected in the same way. Using an individual-based monitoring of 20+ years in free-living population of Alpine swifts (Tachymarptis melba), we investigated age-dependent variation between sexes and between six biometric traits, 4 reproductive traits, and 1 measure of parasite burden. We accounted for selective disappearance and terminal effects in our analyses. Our results provide general support for age-dependent variation at adulthood in 8 out of the 11 traits investigated. Most traits showed a variation with 2 thresholds, with first a strong improvement until 4 to 12 years of age (e.g., increased fork length, decreased parasite load, or earlier laying date) followed by a plateau and a decline at older ages. The age of the second threshold showed sex specific asynchrony, with an earlier threshold in males than in females for tail length, parasite burden and laying date, as well as moderate asynchrony across traits. Rates of senescence differed between sexes, with stronger senescence of the tail in females than in males and with evidence of reproductive senescence in females but not in males. We also found evidence of terminal investment in males with respect to brood size at hatching and terminal decline with increased asymmetry of the fork and decreased body mass. We found evidence of selective appearance with males with longer fork and little fork asymmetry starting to reproduce earlier in life, and females that start to reproduce earlier tending to higher reproductive success. Finally, we found selective disappearance of males with longer tails and marginal effect of selective disappearance of females with lower body mass. We discuss how natural or sexual selection may have led to these trait- and sex-specific patterns of aging in this long-lived bird

Cellular immunity predominates over humoral immunity after homologous and heterologous mRNA and vector-based COVID-19 vaccine regimens in solid organ transplant recipients

Knowledge on the immunogenicity of vector-based and mRNA-vaccines in solid organ transplant recipients is limited. Therefore, SARS-CoV-2–specific T cells and antibodies were analyzed in 40 transplant recipients and 70 controls after homologous or heterologous vaccine-regimens. Plasmablasts and SARS-CoV-2–specific CD4 and CD8 T cells were quantified using flow cytometry. Specific antibodies were analyzed by ELISA and neutralization assay. The two vaccine types differed after the first vaccination, as IgG and neutralizing activity were more pronounced after mRNA priming (p = .0001 each), whereas CD4 and CD8 T cell levels were higher after vector priming (p = .009; p = .0001). All regimens were well tolerated, and SARS-CoV-2–specific antibodies and/or T cells after second vaccination were induced in 100% of controls and 70.6% of transplant recipients. Although antibody and T cell levels were lower in patients, heterologous vaccination led to the most pronounced induction of antibodies and CD4 T cells. Plasmablast numbers were significantly higher in controls and correlated with SARS-CoV-2–specific IgG- and T cell levels. While antibodies were only detected in 35.3% of patients, cellular immunity was more frequently found (64.7%) indicating that assessment of antibodies is insufficient to identify COVID-19-vaccine responders. In conclusion, heterologous vaccination seems promising in transplant recipients, and combined analysis of humoral and cellular immunity improves the identification of responders among immunocompromised individuals

A marker of biological age explains individual variation in the strength of the adult stress response

This research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) under grants BB/J016446/1, BB/J015091/1 and BB/J016292/1. The project has also received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. AdG 666669 (D.N.) and 268926 (P.M.)) K.A.S. was also funded by a BBSRC David Phillips Research Fellowship. The raw data and R script from this experiment are publicly available at: https://doi.org/10.5281/zenodo.846830 [38].The acute stress response functions to prioritize behavioural and physiological processes that maximize survival in the face of immediate threat. There is variation between individuals in the strength of the adult stress response that is of interest in both evolutionary biology and medicine. Age is an established source of this variation-stress responsiveness diminishes with increasing age in a range of species-but unexplained variation remains. Since individuals of the same chronological age may differ markedly in their pace of biological ageing, we asked whether biological age-measured here via erythrocyte telomere length-predicts variation in stress responsiveness in adult animals of the same chronological age. We studied two cohorts of European starlings in which we had previously manipulated the rate of biological ageing by experimentally altering the competition experienced by chicks in the fortnight following hatching. We predicted that individuals with greater developmental telomere attrition, and hence greater biological age, would show an attenuated corticosterone (CORT) response to an acute stressor when tested as adults. In both cohorts, we found that birds with greater developmental telomere attrition had lower peak CORT levels and a more negative change in CORT levels between 15 and 30 min following stress exposure. Our results, therefore, provide strong evidence that a measure of biological age explains individual variation in stress responsiveness: birds that were biologically older were less stress responsive. Our results provide a novel explanation for the phenomenon of developmental programming of the stress response: observed changes in stress physiology as a result of exposure to early-life adversity may reflect changes in ageing.Publisher PDFPeer reviewe

The elephant in the family: Costs and benefits of elder siblings on younger offspring life-history trajectory in a matrilineal mammal

Many mammals grow up with siblings, and interactions between them can influence offspring phenotype and fitness. Among these interactions, sibling competition between different-age offspring should lead to reproductive and survival costs on the younger sibling, while sibling cooperation should improve younger sibling's reproductive potential and survival. However, little is known about the consequences of sibling effects on younger offspring life-history trajectory, especially in long-lived mammals.We take advantage of a large, multigenerational demographic dataset from semi-captive Asian elephants to investigate how the presence and sex of elder siblings influence the sex, survival until 5 years old, body condition, reproductive success (i.e. age at first reproduction and lifetime reproductive success) and long-term survival of subsequent offspring.We find that elder siblings have heterogeneous effects on subsequent offspring life-history traits depending on their presence, their sex and the sex of the subsequent offspring (named focal calf).Overall, the presence of an elder sibling (either sex) strongly increased focal calf long-term survival (either sex) compared to sibling absence. However, elder sisters had higher impact on the focal sibling than elder brothers. Focal females born after a female display higher long-term survival, and decreased age at first reproduction when raised together with an elder sister rather than a brother. Focal males born after a female rather than a male showed lower survival but higher body weight when both were raised together. We did not detect any sibling effects on the sex of the focal calf sex, survival until 5 years old and lifetime reproductive success.​​​​​​​Our results highlight the general complexity of sibling effects, but broadly that elder siblings can influence the life-history trajectory of subsequent offspring. We also stress the importance of considering all life stages when evaluating sibling effects on life trajectories.</ol

Vigilancia del desarrollo infantil: estudio de intervención con enfermeros de la Estrategia Salud de la Familia

Objetivo: avaliar a efetividade de uma ação educativa em vigilância do desenvolvimento infantil, de enfermeiros que atuam na atenção primária à saúde.Métodos: estudo de intervenção do tipo antes-depois, realizado com 45 enfermeiros e 450 mães de crianças menores de 2 anos. Inicialmente, avaliaram-se as práticas e conhecimentos dos enfermeiros quanto à vigilância do desenvolvimento infantil e entrevistaram-se as mães sobre estas práticas. Em seguida, realizaram-se oficinas com enfermeiros e após quatro meses reavaliaram-se os conhecimentos dos enfermeiros e as informações maternas.Resultados: após intervenção houve aumento significativo na frequência dos seguintes aspectos: de 73% para 100%, em relação à prática dos enfermeiros em perguntar a opinião das mães sobre o desenvolvimento dos filhos; de 42% para 91%, quanto à utilização de instrumento sistematizado para avaliação; de 91% para 100%, referente à orientação às mães sobre como estimular o desenvolvimento da criança.Conclusões: a intervenção contribuiu para o aumento dos conhecimentos dos enfermeiros e implementação da vigilância do desenvolvimento infantil, evidenciando a importância desta iniciativa para a melhoria da qualidade do cuidado em saúde da criança.Objective: to evaluate the effectiveness of an educational action in child development surveillance performed by nurses working in primary health care.Methods: interventional study with a before-and-after type of design, carried out with 45 nurses and 450 mothers of children under 2 years of age. Initially, it was evaluated the practices and knowledge of nurses on child development surveillance and the mothers were interviewed about these practices. Subsequently, workshops were carried out with nurses and four months later, the knowledge of nurses and the maternal information were reevaluated.Results: after intervention there was significant increase in the frequency of the following aspects: from 73% to 100%, in relation to the practice of nurses of asking the opinion of mothers about their children's development; from 42% to 91%, regarding the use of the systematized instrument of evaluation; from 91% to 100% with respect to guidance to mothers on how to stimulate child development.Conclusions: the intervention contributed to the increase of knowledge of nurses and implementation of child development surveillance, showing the importance of this initiative to improve the quality of child health care.Objetivo: evaluar la eficacia de una acción educativa en vigilancia del desarrollo infantil, de los enfermeros que trabajan en la atención primaria de salud.Métodos: estudio de intervención, con diseño tipo antes y después, llevado a cabo con 45 enfermeros y 450 madres de niños menores de 2 años. Inicialmente, se evaluó las prácticas y los conocimientos de los enfermeros sobre la vigilancia del desarrollo infantil y se entrevistó a las madres sobre estas prácticas. A continuación, talleres se llevaron a cabo con los enfermeros y después de cuatro meses, se reevaluaron los conocimientos de los enfermeros e la información materna.Resultados: después de la intervención se ha producido un aumento significativo en la frecuencia de los siguientes aspectos: del 73% al 100%, con respecto a la práctica de los enfermeros de preguntar la opinión de las madres sobre el desarrollo de sus hijos; del 42% al 91%, cuanto el uso de instrumento sistematizado para la evaluación; del 91% al 100%, con respecto a la orientación a las madres sobre cómo estimular el desarrollo del niño.Conclusiones: la intervención contribuyó para aumentar el conocimiento de los enfermeros y la implementación de la vigilancia del desarrollo infantil, destacando la importancia de esta iniciativa para mejorar la calidad de la atención a la salud infantil