Alistair M. Senior's research while affiliated with The University of Sydney and other places
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Publications (130)
The metabolic effects of sugars and fat lie at the heart of the “carbohydrate vs fat” debate on the global obesity epidemic. Here, we use nutritional geometry to systematically investigate the interaction between dietary fat and the major monosaccharides, fructose and glucose, and their impact on body composition and metabolic health. Male mice (n...
Importance:
Plant-based diets are known to improve cardiometabolic risk in the general population, but their effects on people at high risk of cardiovascular diseases (CVDs) remain inconclusive.
Objective:
To assess the association of vegetarian diets with major cardiometabolic risk factors, including low-density lipoprotein cholesterol (LDL-C),...
BACKGROUND: Protein leverage (PL), the phenomenon of food consuming until absolute intake of protein meets a target value, regardless of shortfall or overconsuming for other nutrients in the diet and total energy intake (TEI). Evidence for PL was observed in humans, recently in a cohort of youth with obesity. This study aimed to test for PL and the...
Although meta‐analysis has become an essential tool in ecology and evolution, reporting of meta‐analytic results can still be much improved. To aid this, we have introduced the orchard plot, which presents not only overall estimates and their confidence intervals, but also shows corresponding heterogeneity (as prediction intervals) and individual e...
Diet is a key lifestyle component that influences metabolic health through several factors, including total energy intake and macronutrient composition. While the impact of caloric intake on gene expression and physiological phenomenon in various tissues is well described, the influence of dietary macronutrient composition on these parameters is le...
Dietary factors influence male reproductive function in both experimental and epidemiological studies. However, there are currently no specific dietary guidelines for male preconception health. Here, we use the Nutritional Geometry framework to examine the effects of dietary macronutrient balance on reproductive traits in C57BL/6 J male mice. Dieta...
The gut microbiome has been shown to play a role in the relationship between diet and cardiometabolic health. We sought to examine the degree to which key microbial lignan metabolites are involved in the relationship between diet quality and cardiometabolic health using a multidimensional framework. This analysis was undertaken using cross-sectiona...
Background/Objectives
The strong regulation of protein intake can lead to overconsumption of total energy on diets with a low proportion of energy from protein, a process referred to as protein leverage. The protein leverage hypothesis posits that protein leverage explains variation in energy intake and potentially obesity in ecological settings. H...
Aims:
Sleep is a fundamental physiological function and is essential for all animals. Sleep is affected by diet compositions including protein (P) and carbohydrates (C), but there has not been a systematic investigation on the effect of dietary macronutrient balance on sleep.
Main methods:
We used the nutritional geometry framework (NGF) to expl...
Macronutrients are a major component of the human diet. However, few studies have assessed their collective association with mortality. We sought to evaluate the associations of macronutrient intake with all-cause, cardiovascular, and cancer mortality in US adults using a multi-nutrient approach. This prospective cohort analysis used data from the...
1. Although meta-analysis has become an essential tool in ecology and evolution, reporting of meta-analytic results can still be much improved. To aid this, we have introduced the orchard plot, which presents not only overall estimates and their confidence intervals but also shows corresponding heterogeneity (as prediction intervals) and individual...
The log response ratio, lnRR, is the most frequently used effect size statistic for meta‐analysis in ecology. However, often missing standard deviations (SDs) prevent estimation of the sampling variance of lnRR. We propose new methods to deal with missing SDs via a weighted average coefficient of variation (CV) estimated from studies in the dataset...
Background
Human nutrition is a leading modifiable risk factor for the prevention of cardiometabolic diseases. However, most nutritional research focuses on the role of specific nutrients rather than compositional analysis of the diet.
Purpose
We aimed to assess the association of dietary macronutrient composition with various markers of cardiomet...
It is hypothesized that humans exhibit ‘protein leverage’ (PL), whereby regulation of absolute protein intake results in the over-consumption of non-protein food on low percentage protein diets. Testing for PL using dietary surveillance data involves seeking evidence for a negative association between total energy intake and percentage energy from...
Background
Little is known about how normal variation in dietary patterns in humans affects the ageing process. To date, most analyses of the problem have used a unidimensional paradigm, being concerned with the effects of a single nutrient on a single outcome. Perhaps then, our ability to understand the problem has been complicated by the fact tha...
Several studies demonstrate genetic variation in the response to dietary restriction (DR) by replicating treatments across isogenic lines/strains from genetic reference panels. These studies typically quantify the response to DR as an effect size, estimated for each strain separately (e.g., difference in mean lifespan between groups). Such 'no-pool...
Secretory IgA is a key mucosal component ensuring host-microbiota mutualism. Here we use nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, and identify dietary protein as the major driver of secretory IgA production. Protein-driven secretory IgA induction is not mediated by T-cell-dependent pathways or...
Objectives
In utero glycemia is an important determinant of fetal growth. Women with gestational diabetes are more likely to deliver large-for-gestational age babies that are at increased risk for obesity. The maternal nutritional state modulates the development of offspring biological systems during the critical periods of gestation and lactation....
The log response ratio, lnRR, is the most frequently used effect size statistic in ecology. However, missing standard deviations (SDs) are often present in meta-analytic datasets, preventing us from obtaining the sampling variance for lnRR. We propose three new methods to deal with missing SDs. All three methods use the square of the weighted avera...
Animals require specific blends of nutrients that vary across the life course and with circumstances, e.g., health and activity levels. Underpinning and complicating these requirements is that individual traits may be optimised on different dietary compositions leading to nutrition-mediated trade-offs among outcomes. Additionally, the food environm...
Carbohydrates, proteins and lipids are essential nutrients to all animals; however, closely related species, populations, and individuals can display dramatic variation in diet. Here we explore the variation in macronutrient tolerance in Drosophila melanogaster using the Drosophila genetic reference panel, a collection of ~200 strains derived from...
During the vulnerable stages of early life, most ectothermic animals experience hourly and diel fluctuations in temperature as air temperatures change. While we know a great deal about how different constant temperatures impact the phenotypes of developing ectotherms, we know remarkably little about the impacts of temperature fluctuations on the de...
Introduction: There is a large body of evidence detailing the associations of individual macronutrients and fatty acids with all-cause and cardiovascular mortality. Studying nutrients in combination may provide additional information concerning complex associations and interactions.
Hypothesis: We hypothesize that overall macronutrient and fat clas...
Background:
Maternal nutrition is associated with epigenetic and cardiometabolic risk factors in offspring. Research in humans has primarily focused on assessing the impact of individual nutrients.
Objective:
We sought to assess the collective impact of maternal dietary monounsaturated (MUFA), polyunsaturated (PUFA), and saturated fat (SFA) on e...
Background
The role of dietary branched chain amino acids (BCAAs) and their effect on metabolic health is complex. How dietary BCAA levels and their interaction with background nutrition affect health is unclear. Here, we used meta-analysis and meta-regression, together with the nutritional modelling, to analyse the results of rodent studies that i...
Skeletal muscle and adipose tissue insulin resistance are major drivers of metabolic disease. To uncover pathways involved in insulin resistance, specifically in these tissues, we leveraged the metabolic diversity of different dietary exposures and discrete inbred mouse strains. This revealed that muscle insulin resistance was driven by gene-by-env...
Obesity and mood disorders have been linked in a positive feedback loop. However, due to the bidirectional relationship between obesity and mental health, it is not clear whether anxiety is correlated with or caused by consumption of obesogenic diets. Here, we present a meta-analysis on the effects of dietary manipulation on rodent behavior in the...
Nutrient sensing pathways influence metabolic health and aging, offering the possibility that diet might be used therapeutically, alone or with drugs targeting these pathways. We used the Geometric Framework for Nutrition to study interactive and comparative effects of diet and drugs on the hepatic proteome in mice across 40 dietary treatments diff...
Increases in phenotypic variation under extreme (e.g. novel or stressful) environmental conditions is emerging as a crucial process through which evolutionary adaptation can occur. Lack of prior stabilising selection, as well as potential instability of developmental processes in these environments, may lead to a release of phenotypic variation tha...
While diet modulates immunity, its impact on B cell ontogeny remains unclear. Using mixture modelling, a large-scale isocaloric dietary cohort mouse study identified carbohydrate as a major driver of B cell development and function. Increasing dietary carbohydrate increased B cell proportions in spleen, mesenteric lymph node and Peyer’s patches, an...
Recently, Song et al. (2020) conducted a simulation study using different methods to deal with non‐independence resulting from effect sizes originating from the same paper – a common occurrence in ecological meta‐analyses. The main methods that were of interest in their simulations were: 1) a standard random‐effects model used in combination with a...
Reduced protein intake, through dilution with carbohydrate, extends lifespan and improves mid-life metabolic health in animal models. However, with transition to industrialised food systems, reduced dietary protein is associated with poor health outcomes in humans. Here we systematically interrogate the impact of carbohydrate quality in diets with...
Genetic and environmental factors play a major role in metabolic health. However, they do not act in isolation, as a change in an environmental factor such as diet may exert different effects based on an individual’s genotype. Here, we sought to understand how such gene-diet interactions influenced nutrient storage and utilization, a major determin...
The replicability of research results has been a cause of increasing concern to the scientific community. The long-held belief that experimental standardization begets replicability has also been recently challenged, with the observation that the reduction of variability within studies can lead to idiosyncratic, lab-specific results that cannot be...
Background: Maternal nutrition impacts cardiometabolic risk factors in offspring. Research in humans has primarily focused on maternal intake of individual nutrients in isolation. We sought to assess the collective impact of maternal dietary monounsaturated (MUFA), polyunsaturated (PUFA), and saturated fat (SFA) on cardiometabolic risk markers in h...
Little is known about how normal variation in dietary patterns in humans affects the aging process, largely because both nutrition and the physiology of aging are highly complex and multidimensional. Here, we apply the nutritional geometry framework to data from 1560 older adults followed over four years to assess how nutrient intake patterns affec...
Insulin’s activation of PI3K/Akt signalling, stimulates glucose uptake by enhancing delivery of GLUT4 to the cell surface. Here we examined the origins of intercellular heterogeneity in the insulin signalling. Akt activation alone, accounted for ∼ 25% of the variance in GLUT4, indicating additional sources of variance exist. The Akt and GLUT4 respo...
The geometric framework for nutrition has largely been applied to macronutrients in experimental settings. Here, we utilize the framework to examine both macro and micronutrient intake patterns in observational human data. We used nutritional intake patterns (3x 24h recall per visit) of 1754 older Quebecers from the NuAge cohort to predict multi-sy...
Calorie restriction (CR) is a promising strategy to attenuate age-related disease risk. Higher protein diets enhance satiety but may also impair metabolic health and accelerate aging. The effect of higher protein intake on adherence to CR and cardiometabolic markers of healthspan remains unknown. We used the Geometric Framework for Nutrition to exa...
Secretory IgA (sIgA) is a key mucosal component ensuring host-microbiota mutualism. Using nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, we identified dietary protein as the major driver of sIgA production. Protein-driven sIgA induction was not mediated by T cell-dependent pathways or changes in gut...
Significance
We compiled the most extensive dataset to date of corresponding national macronutrient supplies, survival statistics, and economic data. We show that the national macronutrient supply is a strong predictor of the pattern of mortality in different age classes. Our analyses can show how the optimum macronutrient supply that is predicted...
Background
Nutrigenomics aims at understanding the interaction between nutrition and gene information. Due to the complex interactions of nutrients and genes, their relationship exhibits non-linearity. One of the most effective and efficient methods to explore their relationship is the nutritional geometry framework which fits a response surface fo...
Biomedical and clinical sciences are experiencing a renewed interest in the fact that males and females differ in many anatomic, physiological, and behavioral traits. Sex differences in trait variability, however, are yet to receive similar recognition. In medical science, mammalian females are assumed to have higher trait variability due to estrou...
The reproducibility of research results has been a cause of increasing concern to the scientific community. The long-held belief that experimental standardization begets reproducibility has also been recently challenged, with the observation that the reduction of variability within studies can lead to idiosyncratic, lab-specific results that are ir...
Lifestyle, mainly dietary, interventions are first-line treatment for women with polycystic ovary syndrome (PCOS), but the optimal diet remains undefined. We combined a hyperandrogenized PCOS mouse model with a systematic macronutrient approach, to elucidate the impact of dietary macronutrients on the development of PCOS. We identify that an optimu...
There is a great deal of debate on the question of whether or not we know what ageing is (Ref. Cohen et al). Here, we consider what we believe to be the especially confused and confusing case of the ageing of the human immune system, commonly referred to as "immunosenescence". But what exactly is meant by this term? It has been used loosely in the...
At a recent symposium on aging biology, a debate was held as to whether or not we know what biological aging is. Most of the participants were struck not only by the lack of consensus on this core question, but also on many basic tenets of the field. Accordingly, we undertook a systematic survey of our 71 participants on key questions that were rai...
Biomedical and clinical sciences are experiencing a renewed interest in the fact that males and females differ in many anatomic, physiological, and behavioral traits. Sex differences in trait variability, however, are yet to receive similar recognition. In medical science, mammalian females are assumed to have higher trait variability due to estrus...
“Classic” forest plots show the effect sizes from individual studies and the aggregate effect from a meta‐analysis. However, in ecology and evolution meta‐analyses routinely contain over 100 effect sizes, making the classic forest plot of limited use. We surveyed 102 meta‐analyses in ecology and evolution, finding that only 11% use the classic fore...
Meta‐analyses are often used to estimate the relative average values of a quantitative outcome in two groups (e.g., control and experimental groups). However, they may also examine the relative variability (variance) of those groups. For such comparisons, two relatively new effect size statistics, the log‐transformed ‘variability ratio’ (the ratio...
Carbohydrates are the major source of dietary energy, but their role in health and disease remains controversial. Recent epidemiological evidence suggests that the increased consumption of carbohydrates is associated with obesity and increased risk of mortality and dietary trials show that carbohydrate restriction leads to weight loss and improved...
Human‐induced global changes such as nitrogen (N) deposition, climatic warming and rainfall changes have been determined to be common drivers of current plant community dynamics. However, it is unclear if and how the individual and combined effects of these drivers differently influence plant diversity and its relationship with productivity at the...
Marine and freshwater spawning environments present fish sperm with unique challenges, but for both, gametes often signal prior to contact via biochemical interactions through maternally-derived compounds (i.e. eggs and ovarian fluid; OF). For example, when OF is incorporated into the fertilization environment, sperm have been observed to exhibit c...
Key points:
Night time/active phase food restriction for 6 hr impaired glucose intolerance in young male and female mice. Females displayed increased capacity for lipogenesis and triglyceride storage in response to a short daily fast. Females had lower fasting insulin levels and an increased potential for utilizing fat for energy through β-oxidati...
Objective:
The aim of this study was to test the protein leverage hypothesis in a cohort of youth with obesity.
Methods:
A retrospective study was conducted in a cohort of youth with obesity attending a tertiary weight management service. Validated food questionnaires revealed total energy intake (TEI) and percentage of energy intake from carboh...
Meta-analyses are frequently used to quantify the difference in the average values of two groups (e.g., control and experimental treatment groups), but examine the difference in the variability (variance) of two groups. For such comparisons, the two relatively new effect size statistics, namely the log-transformed 'variability ratio' (the ratio of...
‘Classical’ forest plots show the effect sizes from individual studies and the aggregate effect from a meta-analysis. However, in ecology and evolution meta-analyses routinely contain over 100 effect sizes, making the classical forest plot of limited use. We surveyed 102 meta-analyses in ecology and evolution, finding that only 11% use the classica...
Background:
Variations in study quality and design complicate interpretation of the clinical significance of consistently reported changes in copper and iron levels in human Parkinson's disease brain and biofluids.
Methods:
We systematically searched literature databases for quantitative reports of biometal levels in the degenerating substantia...
Increased blood levels of branched chain amino acids (BCAAs) have been associated with cardiometabolic risk factors. Here we studied 918 community dwelling older men to determine the relationship between BCAAs and other amino acids with cardiometabolic risk factors, major cardiovascular endpoints (MACE) and mortality. BCAAs had robust associations...
Protein and branched-chain amino acid (BCAA) intake are associated with changes in circulating BCAAs and influence metabolic health in humans and rodents. However, the relationship between BCAAs and body composition in both species is unclear, with many studies questioning the translatability of preclinical findings to humans. Here, we assessed and...
Genetic and environmental factors contribute to metabolic health. However, they do not act in isolation. Here, we sought to understand how diet and gene interactions influence the ability to store and utilise nutrients, a major determinant of metabolic disease. We subjected the Drosophila Genetic Reference Panel (DGRP), comprising 200 genetically d...
Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets leads to hyperphagia, obesity and re...
Protein and calorie restrictions extend median lifespan in many organisms. However, studies suggest that among-individual variation in the age at death is also affected. Ultimately, both of these outcomes must be caused by effects of nutrition on underlying patterns of age-specific mortality (ASM). Using model life tables, we tested for effects of...
Giant pandas are unusual in belonging to a primarily carnivorous clade and yet being extremely specialized herbivores that feed almost exclusively on highly fibrous bamboo [1]. Paradoxically, they appear inconsistently adapted to their plant diet, bearing a mix of herbivore and carnivore traits. Herbivore traits include a skull, jaw musculature, an...
Stable isotopes are widely used to identify trophic interactions and to determine trophic positions of organisms in food webs. Comparative studies have provided general insights into the variation in isotopic composition between consumers and their diet (discrimination factors) in predator‐prey and herbivore‐plant relationships while other major co...
While there is a burgeoning interest in the effects of nutrition on systemic inflammatory diseases, how dietary macronutrient balance impacts local chronic inflammatory diseases in the mouth has been largely overlooked. Here, we used the Geometric Framework for Nutrition to test how the amounts of dietary macronutrients and their interactions, as w...
Lifespan and fecundity, the main components in evolutionary fitness, are both strongly affected by nutritional state. Geometric framework of nutrition (GFN) experiments has shown that lifespan and fecundity are separated in nutrient space leading to a functional trade-off between the two traits. Here we develop a spatially explicit agent-based mode...
Sperm counts have shown a progressive decline across the world since the mid‐1900s. Global rates of obesity have been climbing at a similarly alarming rate, suggesting that these two factors may be linked. However, studies examining the relationship between body mass index (BMI) and male fertility have produced conflicting results. These discrepanc...
Calorie restriction (CR) increases lifespan and improves brain health in mice. Ad libitum low-protein, high-carbohydrate (LPHC) diets also extend lifespan, but it is not known whether they are beneficial for brain health. We compared hippocampus biology and memory in mice subjected to 20% CR or provided ad libitum access to one of three LPHC diets...