An experimental demonstration that early-life competitive disadvantage accelerates telomere loss.

Adverse experiences in early life can exert powerful delayed effects on adult survival and health. Telomere attrition is a potentially important mechanism in such effects. One source of early-life adversity is the stress caused by competitive disadvantage. Although previous avian experiments suggest that competitive disadvantage may accelerate telomere attrition, they do not clearly isolate the effects of competitive disadvantage from other sources of variation. Here, we present data from an experiment in European starlings (Sturnus vulgaris) that used cross-fostering to expose siblings to divergent early experience. Birds were assigned either to competitive advantage (being larger than their brood competitors) or competitive disadvantage (being smaller than their brood competitors) between days 3 and 12 post-hatching. Disadvantage did not affect weight gain, but it increased telomere attrition, leading to shorter telomere length in disadvantaged birds by day 12. There were no effects of disadvantage on oxidative damage as measured by plasma lipid peroxidation. We thus found strong evidence that early-life competitive disadvantage can accelerate telomere loss. This could lead to faster age-related deterioration and poorer health in later life.

Nogo receptor-Fc delivered by haematopoietic cells enhances neurorepair in a multiple sclerosis model.

Nogo receptor 1 is the high affinity receptor for the potent myelin-associated inhibitory factors that make up part of the inflammatory extracellular milieu during experimental autoimmune encephalomyelitis. Signalling through the Nogo receptor 1 complex has been shown to be associated with axonal degeneration in an animal model of multiple sclerosis, and neuronal deletion of this receptor homologue, in a disease specific manner, is associated with preserving axons even in the context of neuroinflammation. The local delivery of Nogo receptor(1-310)-Fc, a therapeutic fusion protein, has been successfully applied as a treatment in animal models of spinal cord injury and glaucoma. As multiple sclerosis and experimental autoimmune encephalomyelitis exhibit large numbers of inflammatory cell infiltrates within the CNS lesions, we utilized transplantable haematopoietic stem cells as a cellular delivery method of the Nogo receptor(1-310)-Fc fusion protein. We identified CNS-infiltrating macrophages as the predominant immune-positive cell type that overexpressed myc-tagged Nogo receptor(1-310)-Fc fusion protein at the peak stage of experimental autoimmune encephalomyelitis. These differentiated phagocytes were predominant during the extensive demyelination and axonal damage, which are associated with the engulfment of the protein complex of Nogo receptor(1-310)-Fc binding to myelin ligands. Importantly, mice transplanted with haematopoietic stem cells transduced with the lentiviral vector carrying Nogo receptor(1-310)-Fc and recovered from the peak of neurological decline during experimental autoimmune encephalomyelitis, exhibiting axonal regeneration and eventual remyelination in the white matter tracts. There were no immunomodulatory effects of the transplanted, genetically modified haematopoietic stem cells on immune cell lineages of recipient female mice induced with experimental autoimmune encephalomyelitis. We propose that cellular delivery of Nogo receptor(1-310)-Fc fusion protein through genetically modified haematopoietic stem cells can modulate multifocal experimental autoimmune encephalomyelitis lesions and potentiate neurological recovery.

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

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.

Early life adversity increases foraging and information gathering in European starlings, Sturnus vulgaris.

Animals can insure themselves against the risk of starvation associated with unpredictable food availability by storing energy reserves or gathering information about alternative food sources. The former strategy carries costs in terms of mass-dependent predation risk, while the latter trades off against foraging for food; both trade-offs may be influenced by an individual's developmental history. Here, we consider a possible role of early developmental experience in inducing different mass regulation and foraging strategies in European starlings. We measured the body mass, body condition, foraging effort, food consumption and contrafreeloading (foraging for food hidden in sand when equivalent food is freely available) of adult birds (≥10 months old) that had previously undergone a subtle early life manipulation of food competition (cross-fostering into the highest or lowest ranks in the brood size hierarchy when 2-12 days of age). We found that developmentally disadvantaged birds were fatter in adulthood and differed in foraging behaviour compared with their advantaged siblings. Disadvantaged birds were hyperphagic compared with advantaged birds, but only following a period of food deprivation, and also spent more time contrafreeloading. Advantaged birds experienced a trade-off between foraging success and time spent contrafreeloading, whereas disadvantaged birds faced no such trade-off, owing to their greater foraging efficiency. Thus, developmentally disadvantaged birds appeared to retain a phenotypic memory of increased nestling food competition, employing both energy storage and information-gathering insurance strategies to a greater extent than their advantaged siblings. Our results suggest that subtle early life disadvantage in the form of psychosocial stress and/or food insecurity can leave a lasting legacy on foraging behaviour and mass regulation even in the absence of food insufficiency during development or adulthood.

Developmental and familial predictors of adult cognitive traits in the European starling.

In birds, there is evidence that adult cognitive traits can both run in families and be affected by early developmental influences. However, different studies use different cognitive tasks, which may not be measuring the same traits, and also focus on different developmental factors. We report results from a study in which we administered multiple cognitive tasks (autoshaping, discrimination learning, reversal learning, progressive ratio schedule, extinction learning and impulsivity) to a cohort of 34 European starlings, Sturnus vulgaris, for which several early developmental measures were available. The cohort consisted of siblings raised either apart or together, whose position in the size hierarchy of the rearing brood had been experimentally manipulated. We examined how the different cognitive measures covaried, the extent to which they ran in families, and which of the developmental factors predicted which of the cognitive outcomes. We found that discrimination and reversal learning speeds were positively correlated, as were breakpoint on the progressive ratio schedule and resistance to extinction. Otherwise, the cognitive measures were uncorrelated, suggesting that they reflected different underlying traits. All traits except discrimination and reversal learning speed ran in families to a substantial extent. Using a model selection approach, we found evidence that natal brood size and developmental telomere attrition (the extent to which the birds' erythrocyte telomeres shortened in early life, an integrative measure of developmental stress) were related to several adult cognitive measures. Results are discussed with respect to the best way of measuring avian cognitive abilities, and the utility of developmental telomere attrition as a predictor of adult outcomes.

Early life disadvantage strengthens flight performance trade-offs in European starlings, Sturnus vulgaris.

Developmental stress has been shown to affect adult flight performance in birds, with both negative and positive effects reported in the literature. Previous studies have used developmental manipulations that had substantial effects on patterns of growth. They have also examined mean levels of flight performance per individual, rather than investigating how developmental stress might alter trade-offs between different components of flight performance. We recorded multiple components of escape flight performance in 20 adult European starlings previously subjected to a manipulation likely to have altered levels of developmental stress. Siblings had been cross-fostered to nests where they were either slightly larger (advantaged treatment) or slightly smaller (disadvantaged treatment) than their competitors. The manipulation had no detectable effect on growth. However, developmental treatment affected performance in escape flights a year later by strengthening the trade-offs between different flight parameters. Disadvantaged birds faced a steeper trade-off between take-off speed and take-off angle, and a steeper trade-off between take-off angle and total time in flight, than advantaged birds. The results suggest that even subtle early life adversity that has no obvious effect on growth or size can leave a lasting legacy in the form of constraints on locomotor performance later in life.

The memory of hunger: developmental plasticity of dietary selectivity in the European starling, Sturnus vulgaris.

The decision to consume toxic prey is a trade-off between the benefits of obtaining nutrients and the costs of ingesting toxins. This trade-off is affected by current state: animals will consume more toxic prey if they are food deprived. However, whether the trade-off is affected by developmental history is currently unknown. We studied the decision to eat quinine-injected mealworms in adult starling siblings that had been exposed to either high or low levels of food competition as chicks, via a brood size manipulation. At the time of our experiments, the two groups of birds did not differ in size, body weight or current environment. Each bird was presented with the toxic prey while living on a high-quality diet and a low-quality diet. We found an effect of diet, with birds consuming more toxic prey while on the low-quality diet, and also of developmental history, with birds from the high-competition brood size treatment eating more toxic prey than their low-competition siblings. The effects of brood size treatment were not completely mediated by early growth, although we did find evidence that early growth affected toxic prey consumption independently of brood size treatment. We discuss our results in relation to adaptive developmental plasticity and the developmental origins of behavioural variation.