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Ivimey-Cook, E. R.

Publications and source records attributed to Ivimey-Cook, E. R..

9 recordsLinked to original sources

Increased stress in early life epigenetically rewires pathways related to aging and longevity

Environmental conditions experienced early in life have profound consequences for vertebrate health, yet the molecular pathways linking developmental stress to aging and reduced lifespan remain poorly understood. Through a novel highly accurate epigenetic clock, developed from RRBS-based blood DNA methylation profiles, we show that experimental lifespan-reducing early-life stress rapidly accelerates epigenetic age in zebra finch chicks (Taeniopygia guttata). Corticosterone-treated 29-day-old chicks share differentially methylated loci with non-treated aged birds and cluster with 6-month-old birds. The transcriptional repressor ZBTB16 emerges as an epigenetically top age-correlated gene and is strongest affected by corticosterone. Elevated developmental corticosterone causes rapid epigenetic remodelling of metabolic pathways well-established in aging and longevity. Our results demonstrate epigenetic rewiring of the aging trajectory through conserved stress-survival mechanisms immediately following elevated early-life stress exposure.

developmental biology↗

Cross-species meta-analysis reveals determinants of homing gene drive performance

Homing gene drives can bias their inheritance above Mendelian expectations, but reported outcomes vary widely. We compiled a cross-species dataset of nearly one million scored progeny from 42 publications reporting CRISPR/Cas9 endonuclease-based gene drives in 10 model, pest, and vector species. Using multilevel meta-analytic models, we evaluate biological, cross, and transgene design factors as predictors of biased drive inheritance. Species is the strongest predictor, but most heterogeneity remains unexplained; design features each explain a modest fraction of the remaining variation, with large construct-to-construct differences pointing to the full combination of design choices rather than any single factor. Nuclease expression timing, the most common optimization target, has limited predictive value after accounting for correlated factors, and predictions do not transfer well between species. Maternal nuclease deposition has a marginal effect on drive inheritance but dramatically increases somatic phenotype rates in offspring, revealing a tissue-of-action rather than repair-outcome effect. An interactive web tool enables community analysis of this dataset, which will guide the design of more efficient gene drives for genetic vector control, invasive species management and other applications. https://sverkuijl.shinyapps.io/GeneDrive/

bioengineering↗

Fasting increases investment in soma upon refeeding at the cost of gamete quality in zebrafish

Fasting increases lifespan in invertebrates, improves biomarkers of health in vertebrates, and is increasingly proposed as a promising route to improve human health. Nevertheless, little is known about how fasted animals use resources upon refeeding, and how such decisions affect putative trade-offs between somatic growth and repair, reproduction, and gamete quality. Such fasting-induced trade-offs are based on strong theoretical foundations and have been recently discovered in invertebrates, but the data on vertebrates is lacking. Here we report that fasted female zebrafish, Danio rerio, increase investment in soma upon refeeding but it comes at a cost of egg quality. Specifically, an increase in fin re-growth was accompanied by a reduction in 24-hours post-fertilization offspring survival. Refed males showed a reduction in sperm velocity and impaired 24-hour post-fertilisation offspring survival. These findings underscore the necessity of considering the impact on eggs and sperm when assessing evolutionary and biomedical implications of lifespan-extending treatments in females and males and call for careful evaluation of the effects of fasting (both during and post) on fertilisation.

evolutionary biology↗

The distribution of the Lansing Effect across animal species

Maternal senescence is a reduction in individual performance associated with an increase in its mothers age at conception. When manifested on adult lifespan, this is known as the Lansing Effect. Single-species studies report both maternal age-related increases and decreases in adult lifespan, but no comprehensive review of the literature has yet determined if the Lansing Effect is a widespread phenomenon. To address this knowledge gap, we performed a meta-analysis of maternal aging rates taken from all available published studies. We recovered 74 estimates from 20 studies representing 14 species. All studies taken together suggest a propensity for a Lansing Effect with an estimated average effect of maternal age on adult lifespan of between -22% to -17% (the lifespan response to an increase in maternal age expressed in the same time units), depending upon our specific choice of model. We failed to find a significant effect of animal class or insect order, but given the oversampling of insect species in the published literature and the paucity of vertebrate studies, we infer that only rotifers and insects demonstrate a tendency for expressing the phenomenon.

evolutionary biology↗

Genetic and thermal variation influences adaptation to fluctuating temperature in the seed beetle, Callosobruchus maculatus

Climate change is associated with both the increase in mean and variability of thermal conditions. The use of more realistic thermal regimes is therefore the most appropriate laboratory method to correctly predict population responses to thermal heterogeneity. However, both the long- and short-term implications of evolving under such conditions are not well understood. Here, we examined the effect of fluctuating daily temperatures on several key life history traits in the seed beetle, Callosobruchus maculatus, that was exposed to a short-term thermal switch into a novel environment. Populations were kept for 19 generations at one of two temperatures: constant control temperature (T=29{degrees}C) or a fluctuating daily cycle (Tmean=33{degrees}C, Tmax=40{degrees}C, and Tmin=26{degrees}C) and were subsequently exposed to a switch to the opposite condition. We found that beetles that had evolved in stressful environments were smaller in size when switched to a constant 29{degrees}C and had far greater reproductive fitness compared to beetles from both the constant control and continuously stressful 33{degrees}C environments. This suggests that beetles raised in environments with stressful fluctuating temperatures were more phenotypically plastic and had greater genetic variability than control treatment beetles and indicates that populations that experience fluctuations in temperature may be better able to respond to short-term changes in environmental conditions.

evolutionary biology↗

Biparental age effects in the burying beetle Nicrophorus vespilloides

Parental age at reproduction influences offspring size and survival by affecting prenatal and postnatal conditions in a wide variety of species, including humans. However, most investigations into this manifestation of ageing focus upon maternal age effects; the effects of paternal age and interactions between maternal and paternal age are often neglected. Furthermore, even when maternal age effects are studied, pre- and postnatal effects are confounded. Using a cross-fostered experimental design, we investigated the joint effects of paternal and pre- and postnatal maternal ages on numerous offspring outcomes in a laboratory population of a species of burying beetle, Nicrophorus vespilloides. When we correct our tests for significance for multiple comparisons, we found no clear evidence for any parental effect senescence acting on egg size, larval weight, or larval survival. Nor did we find a statistical effect of paternal or egg producer age on the outcomes of foster mothers as measured by weight change experienced during caregiving. These findings are consistent with recent negative results reported in a similar study of N. vespilloides maternal age effects while also expanding these to other offspring traits and to paternal age effects. We discuss how the peculiar life history of this species may promote selection to resist the evolution of parental age effects, and how this might have influenced our ability to detect senescence.

evolutionary biology↗

Inbreeding reduces fitness of seed beetles under thermal stress

Human-induced environmental change can influence populations both at the global level through climatic warming and at the local level through habitat fragmentation. As populations become more isolated, they can suffer from high levels of inbreeding which contributes to a reduction in fitness, termed inbreeding depression. However, it is still unclear if this increase in homozygosity also results in a corresponding increase in sensitivity to stressful conditions, which could intensify the already detrimental effects of environmental warming. Here, in a fully factorial design, we assessed the life-long impact of increased mutation load and elevated temperature on key life history traits in the seed beetle, Callosobruchus maculatus. We found that beetles raised at higher temperatures had far reduced fitness and survival than beetles from control temperatures. Importantly, these negative effects were exacerbated in inbred beetles as a result of increased mutation load, with further detrimental effects manifesting on individual hatching probability and lifetime reproductive success. These results reveal the harmful impact that increasing temperature and likelihood of habitat fragmentation due to anthropogenetic changes in environmental conditions could have on populations of organisms worldwide.

evolutionary biology↗

Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans

Dietary restriction increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here we investigated the effect of dietary restriction by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in C. elegans. We show that while TF robustly reduces mortality risk and improves late-life reproduction in the parental generation (P0), it has a wide range of both positive and deleterious effects on future generations (F1-F3). Remarkably, great-grandparental exposure to TF in early-life reduces fitness and increases mortality risk of F3 descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of dietary restriction underscoring the need to consider fitness of future generations in pursuit of healthy ageing.

evolutionary biology↗

Evaluating the diversity of maternal age effects upon neonatal survival across animal species

Maternal effect senescence is the detrimental effect of increased maternal age on offspring performance. Despite much recent interest given to describing this phenomenon, its origins and distribution across the tree-of-life are poorly understood. We find that age affects neonatal survival in 83 of 90 studies across 51 species, but we observed a puzzling difference between groups of animal species. Amongst wild bird populations, the average effect of age was only -0.7% per standardized unit of increasing age, but maternal effects clearly senesced in laboratory invertebrates (-67.1%) and wild mammals (-57.8%). Comparisons amongst demographic predictions derived from evolutionary theory and conventional demographic models suggest that natural selection has shaped maternal effect senescence in the natural world. These results emphasize both the general importance of maternal age effects and the potential for evolutionary genetics to provide a valuable framework for understanding the diversity of this manifestation of ageing in animal species.

evolutionary biology↗