The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways.

The evolutionary context of why caloric restriction (CR) activates physiological mechanisms that slow the process of aging remains unclear. The main goal of this analysis was to identify, using metabolomics, the common pathways that are modulated across multiple tissues (brown adipose tissue, liver, plasma, and brain) to evaluate two alternative evolutionary models: the "disposable soma" and "clean cupboards" ideas. Across the four tissues, we identified more than 10,000 different metabolic features. CR altered the metabolome in a graded fashion. More restriction led to more changes. Most changes, however, were tissue specific, and in some cases, metabolites changed in opposite directions in different tissues. Only 38 common metabolic features responded to restriction in the same way across all four tissues. Fifty percent of the common altered metabolites were carboxylic acids and derivatives, as well as lipids and lipid-like molecules. The top five modulated canonical pathways were l-carnitine biosynthesis, NAD (nicotinamide adenine dinucleotide) biosynthesis from 2-amino-3-carboxymuconate semialdehyde, S-methyl-5'-thioadenosine degradation II, NAD biosynthesis II (from tryptophan), and transfer RNA (tRNA) charging. Although some pathways were modulated in common across tissues, none of these reflected somatic protection, and each tissue invoked its own idiosyncratic modulation of pathways to cope with the reduction in incoming energy. Consequently, this study provides greater support for the clean cupboards hypothesis than the disposable soma interpretation.

Knowing the fishery to know the bycatch: bias-corrected estimates of harbour porpoise bycatch in gillnet fisheries.

Incidental captures (bycatch) remain a key global conservation threat for cetaceans. Bycatch of harbour porpoise Phocoena phocoena in set gillnets is routinely monitored in European Union fisheries, but generally relies on data collected at low spatio-temporal resolution or over short periods. In Denmark, a long-term monitoring programme started in 2010 using electronic monitoring to collect data on porpoise bycatch and gillnet fishing effort at a fine spatial and temporal scale, including time and position of each fishing operation, together with every associated bycatch event. We used these observations to model bycatch rates, given the operational and ecological characteristics of each haul observed in Danish waters. Data on fishing effort from the Danish and Swedish gillnet fleets were collected to predict fleet-wide porpoise bycatch in gillnets at regional level. Between 2010 and 2020, yearly total bycatch averaged 2088 animals (95% Cl: 667-6798). For the Western Baltic assessment unit, bycatch levels were above sustainability thresholds. These results demonstrate that fishing characteristics are key determinants of porpoise bycatch and that classical approaches ignoring these features would produce biased estimates. It emphasizes the need for efficient and informative monitoring methods to understand possible conservation impacts of marine mammal bycatch and to implement tailored mitigation techniques.

Disparities in greenspace access during COVID-19 mobility restrictions.

More than half of the human population lives in cities and therefore predominantly experience nature in urban greenspace, an important contributor to wellbeing. As the world faces a pandemic which threatens the physical and mental health of billions of people, it is crucial to understand that all have the possibility to access nature exposure to alleviate some of these challenges. Here, for the first time, we integrate data from Facebook, Twitter, and Google Search users to show that people looked for greenspace during COVID-19 mobility restrictions but may not have always managed to reach it. We used a longitudinal approach, replicated in three European cities, to assess whether people spent more time in locations with more greenspace, and whether this change in urban density remained for the whole pandemic, pre-vaccine, period. We coupled this human density study with a longitudinal study of web search patterns for Parks and online discussion about urban greenspace. People searched for Parks near them more during the pandemic, particularly when they were allowed to visit them. They discussed in positive terms greenspace particularly more at the start of the pandemic. People spent more time in areas with greenspace when they could and that depended on the level of multiple deprivation of their neighbourhood. Importantly, while people sought greenspace throughout the first 20 months of the pandemic, this preference intensified through the waves of lockdown. Living in an affluent area conferred a greenspace advantage in London and Paris but we find that in Berlin greenspace in more deprived neighbourhoods were used more. Overall, urban greenspace occupied a greater place in people's lives during the pandemic. Whether people could realise greenspace access depended on the deprivation level of the neighbourhood. Public greenspace access should be integrated in national indices of deprivation given its importance for wellbeing.

Metabolic response of dolphins to short-term fasting reveals physiological changes that differ from the traditional fasting model.

Bottlenose dolphins (Tursiops truncatus) typically feed on prey that are high in lipid and protein content and nearly devoid of carbohydrate, a dietary feature shared with other marine mammals. However, unlike fasted-adapted marine mammals that predictably incorporate fasting into their life history, dolphins feed intermittently throughout the day and are not believed to be fasting-adapted. To assess whether the physiological response to fasting in the dolphin shares features with or distinguishes them from those of fasting-adapted marine mammals, the plasma metabolomes of eight bottlenose dolphins were compared between post-absorptive and 24-h fasted states. Increases in most identified free fatty acids and lipid metabolites and reductions in most amino acids and their metabolites were consistent with the upregulation of lipolysis and lipid oxidation and the downregulation of protein catabolism and synthesis. Consistent with a previously hypothesized diabetic-like fasting state, fasting was associated with elevated glucose and patterns of certain metabolites (e.g. citrate, cis-aconitate, myristoleic acid) indicative of lipid synthesis and glucose cycling to protect endogenous glucose from oxidative disposal. Pathway analysis predicted an upregulation of cytokines, decreased cell growth and increased apoptosis including apoptosis of insulin-secreting ß-cells. Metabolomic conditional mutual information networks were estimated for the post-absorptive and fasted states and 'topological modules' were estimated for each using the eigenvector approach to modularity network division. A dynamic network marker indicative of a physiological shift toward a negative energy state was subsequently identified that has the potential conservation application of assessing energy state balance in at-risk wild dolphins.

Predicting the effects of human developments on individual dolphins to understand potential long-term population consequences.

Human activities that impact wildlife do not necessarily remove individuals from populations. They may also change individual behaviour in ways that have sublethal effects. This has driven interest in developing analytical tools that predict the population consequences of short-term behavioural responses. In this study, we incorporate empirical information on the ecology of a population of bottlenose dolphins into an individual-based model that predicts how individuals' behavioural dynamics arise from their underlying motivational states, as well as their interaction with boat traffic and dredging activities. We simulate the potential effects of proposed coastal developments on this population and predict that the operational phase may affect animals' motivational states. For such results to be relevant for management, the effects on individuals' vital rates also need to be quantified. We investigate whether the relationship between an individual's exposure and the survival of its calves can be directly estimated using a Bayesian multi-stage model for calf survival. The results suggest that any effect on calf survival is probably small and that a significant relationship could only be detected in large, closely studied populations. Our work can be used to guide management decisions, accelerate the consenting process for coastal and offshore developments and design targeted monitoring.

Managing the wildlife tourism commons.

The nonlethal effects of wildlife tourism can threaten the conservation status of targeted animal populations. In turn, such resource depletion can compromise the economic viability of the industry. Therefore, wildlife tourism exploits resources that can become common pool and that should be managed accordingly. We used a simulation approach to test whether different management regimes (tax, tax and subsidy, cap, cap and trade) could provide socioecologically sustainable solutions. Such schemes are sensitive to errors in estimated management targets. We determined the sensitivity of each scenario to various realistic uncertainties in management implementation and in our knowledge of the population. Scenarios where time quotas were enforced using a tax and subsidy approach, or they were traded between operators were more likely to be sustainable. Importantly, sustainability could be achieved even when operators were assumed to make simple rational economic decisions. We suggest that a combination of the two regimes might offer a robust solution, especially on a small spatial scale and under the control of a self-organized, operator-level institution. Our simulation platform could be parameterized to mimic local conditions and provide a test bed for experimenting different governance solutions in specific case studies.

Resilience of human-nature interaction network to pandemic conditions.

Cultural ecosystem services (CES) contribute to maintaining and improving human well-being. Understanding the network of interactions involved in co-producing CES is essential for maximizing well-being. In this study, we used social media data to estimate a CES network and assess human-nature interactions underpinning CES co-production. We employed a replicable bottom-up approach, using 682,000 Reddit posts to define a comprehensive repertoire of nature features and human activities, and then sampled the co-occurrence of these features and activities reported in 41.7 million tweets from 2018 to 2022. We expected to observe large changes in the CES network topology in relation to mobility restrictions during the COVID-19 pandemic, but instead the CES network was resilient. However, there was an impulse on the link between self care activities and urban greenspace. This demonstrates that urban greenspaces facilitated local CES production and, thus, provided resilience for maintaining well-being during the pandemic. This study emphasizes the importance of promoting access to nature features that provide CES within local communities.

Minke whales maximise energy storage on their feeding grounds.

Seasonal trends in energy storage of the minke whale (Balaenoptera acutorostrata), a capital breeder, were investigated in Iceland, a North Atlantic feeding ground. The aim was to better understand the energy acquisition strategies of minke whales and the energetic costs that different reproductive classes face during the breeding season. We modelled total blubber volume, using blubber thickness and morphometric measurements of individual whales. Blubber volume was influenced by body length, and was higher for pregnant females than mature whales. Blubber volume increased linearly through the feeding season at the same rate for mature (mean ± s.e.m.=0.0028 ± 0.00103 m(3) day(-1); N=61 male, 5 female) and pregnant whales (0.0024 ± 0.00100 m(3) day(-1); N=49), suggesting that minke whales aim to maximise energy storage while on the feeding grounds. The total amount of blubber accumulated over the feeding season (0.51 ± 0.119 m(3) for mature and 0.43 ± 0.112 m(3) for pregnant whales), together with energy stored as muscle and intra-abdominal fats, constitutes the total amount of energy available for reproduction (fetus development and lactation) on the breeding grounds, as well as migration, daily field metabolic rates, growth and body maintenance. No seasonal variation was observed for immature whales (N=4 male, 12 female), suggesting that they are investing most of their excess energy into growth rather than reproduction, in order to reach the length of sexual maturity faster and start reproducing earlier. Our novel modelling approach provides insight into large whale bioenergetics and life history strategies, as well as the relationship between single-site measurement of blubber thickness and total blubber volume.

Network modularity promotes cooperation.

Cooperation in animals and humans is widely observed even if evolutionary biology theories predict the evolution of selfish individuals. Previous game theory models have shown that cooperation can evolve when the game takes place in a structured population such as a social network because it limits interactions between individuals. Modularity, the natural division of a network into groups, is a key characteristic of all social networks but the influence of this crucial social feature on the evolution of cooperation has never been investigated. Here, we provide novel pieces of evidence that network modularity promotes the evolution of cooperation in 2-person prisoner's dilemma games. By simulating games on social networks of different structures, we show that modularity shapes interactions between individuals favouring the evolution of cooperation. Modularity provides a simple mechanism for the evolution of cooperation without having to invoke complicated mechanisms such as reputation or punishment, or requiring genetic similarity among individuals. Thus, cooperation can evolve over wider social contexts than previously reported.

Emergent interactions in the management of multiple threats to the conservation of harbour porpoises.

Human activities at sea are intensifying and diversifying. This is leading to more complex interactions of anthropogenic impacts requiring adaptable management interventions to mitigate their cumulative effects on biodiversity conservation and restoration objectives. Bycatch remains the dominant conservation threat for coastal cetaceans. Additionally, the indirect impact of repeated exposure to disturbances, particularly acoustic disturbances, can affect cetacean population growth and therefore conservation objectives. Pingers are used to ensonify nets to provide an effective mitigation of bycatch risk. As those become more prevalent across fisheries at risk to catch for example harbour porpoises, pingers become contributors to the anthropogenic noise landscape which may affect the vital rates of this species as well. Currently, we do not know how to best balance pinger prevalence to minimise both bycatch rate and the population consequences of acoustic disturbance (PCoD). Here we use an agent-based model to determine how pinger prevalence in nets can be adjusted to minimise bycatch rate and noise disturbance propagating to affect population growth for harbour porpoises. We show that counter-intuitively bycatch rate can increase at lower pinger prevalence. When ecological conditions are such that PCOD can emerge, higher prevalence of pingers can lead to indirect effects on population growth. This would result from condition-mediated decreased reproductive potential. Displacing fishing effort, via time-area closure, can be an effective mitigation strategy in these circumstances. These findings have important implications for current management plans which, for practical consideration, may lead to lower overall pinger prevalence at sea. This study also shows that estimating the reproductive potential of the species should be incorporated in bycatch monitoring programmes. We now need to better understand how physiological condition affect reproductive decisions and behavioural responses to noise in cetaceans to better appraise and estimate the cumulative impacts of bycatch and its mitigations.

Bleak prospects and targeted actions for achieving the Sustainable Development Goals.

At the mid-point to 2030, progress towards achieving the Sustainable Development Goals (SDGs) varies significantly across countries. While the classification of countries can lay the foundation for improving policy efficiency and promoting joint action, bottom-up, SDG data-driven country classifications have largely remained unexplored. Here, we classified 166 countries based on their performances in the 17 SDGs and further used the classification to analyze SDG interactions and compare development aid distributions. The countries were classified into five groups, ranging from "lowest development with good environment" to "high development needing climate action". None of them scored highly in all SDGs, and due to trade-offs related to environment and climate SDGs, none of them can achieve all SDGs eventually. To maximize the potential for achieving the SDGs, all countries need to undergo a sustainable transformation, and prioritizing certain SDGs, such as SDG 9 (industry, innovation and infrastructure), can help countries with lower sustainable development levels achieve more with less. Furthermore, global development aid should be better aligned with country needs, particularly in areas of education, energy, environment, and water supply and sanitation. By better characterizing different countries, this study reveals the bleak prospects of achieving all SDGs and provides valuable insights into more targeted actions for national sustainable development and global collaboration.

The Effects of Graded Levels of Calorie Restriction: XIX. Impact of Graded Calorie Restriction on Protein Expression in the Liver.

Calorie restriction (CR) extends life span by modulating the mechanisms involved in aging. We quantified the hepatic proteome of male C57BL/6 mice exposed to graded levels of CR (0%-40% CR) for 3 months, and evaluated which signaling pathways were most affected. The metabolic pathways most significantly stimulated by the increase in CR, included the glycolysis/gluconeogenesis pathway, the pentose phosphate pathway, the fatty acid degradation pathway, the valine, leucine, and isoleucine degradation pathway, and the lysine degradation pathway. The metabolism of xenobiotics by cytochrome P450 pathway was activated and feminized by increased CR, while production in major urinary proteins (Mups) was strongly reduced, consistent with a reduced investment in reproduction as predicted by the disposable soma hypothesis. However, we found no evidence of increased somatic protection, and none of the 4 main pathways implied to be linked to the impact of CR on life span (insulin/insulin-like growth factor [IGF-1], nuclear factor-κB [NF-κB], mammalian Target of Rapamycin [mTOR], and sirtuins) as well as pathways in cancer, were significantly changed at the protein level in relation to the increase in CR level. This was despite previous work at the transcriptome level in the same individuals indicating such changes. On the other hand, we found Aldh2, Aldh3a2, and Aldh9a1 in carnitine biosynthesis and Acsl5 in carnitine shuttle system were up-regulated by increased CR, which are consistent with our previous work on metabolome of the same individuals. Overall, the patterns of protein expression were more consistent with a "clean cupboards" than a "disposable soma" interpretation.

Animal social networks as substrate for cultural behavioural diversity.

We used individual-based stochastic models to examine how social structure influences the diversity of socially learned behaviour within a non-human population. For continuous behavioural variables we modelled three forms of dyadic social learning, averaging the behavioural value of the two individuals, random transfer of information from one individual to the other, and directional transfer from the individual with highest behavioural value to the other. Learning had potential error. We also examined the transfer of categorical behaviour between individuals with random directionality and two forms of error, the adoption of a randomly chosen existing behavioural category or the innovation of a new type of behaviour. In populations without social structuring the diversity of culturally transmitted behaviour increased with learning error and population size. When the populations were structured socially either by making individuals members of permanent social units or by giving them overlapping ranges, behavioural diversity increased with network modularity under all scenarios, although the proportional increase varied considerably between continuous and categorical behaviour, with transmission mechanism, and population size. Although functions of the form e(c)¹(m)⁻(c)² + (c)³(Log(N)) predicted the mean increase in diversity with modularity (m) and population size (N), behavioural diversity could be highly unpredictable both between simulations with the same set of parameters, and within runs. Errors in social learning and social structuring generally promote behavioural diversity. Consequently, social learning may be considered to produce culture in populations whose social structure is sufficiently modular.

Untargeted plasma metabolomic analysis of wild bottlenose dolphins (Tursiops truncatus) indicate protein degradation when in poorer health.

Cumulative exposure to sub-lethal anthropogenic stressors can affect the health and reproduction of coastal cetaceans and hence their population viability. To date, we do not have a clear understanding of the notion of health for cetaceans in an ecological context; that is, how health status affects the ability of individuals to survive and reproduce. Here, we make use of a unique health-monitoring programme of estuarine bottlenose dolphins in South Carolina and Florida to determine de novo changes in biological pathways, using untargeted plasma metabolomics, depending on the health status of individuals obtained from veterinary screening. We found that individuals that were in a poor health state had lower circulating amino acids pointing towards increased involvement of gluconeogenesis (i.e., new formation of glucose). More mechanistic work is needed to disentangle the interconnection between health and energy metabolism in cetaceans to mediate potential metabolic constraints they may face during periods of stress.

The biogeography of group sizes in humpback dolphins (Sousa spp.).

Humpback dolphins (Sousa spp.) are obligate shallow-water and resident species, and they typically live in fission-fusion societies composed of small-sized groups with changeable membership. However, we have scant knowledge of their behavioral ecology, starting with potential factors influencing inter-population variability of their group sizes. Here, we compiled a new global dataset of humpback dolphin group sizes based on 150 published records. Our data indicated an inter-specific consistency of group-living strategy among the 4 species in the Sousa genus, as these species preferred living in small-sized groups with a mean size of mostly no more than 10, a minimum size of single individual or small pairs, and a maximum size of several tens or ≈100. In addition, we clearly showed the geographic variations in group sizes of humpback dolphins at a global scale. We found that the geographic variations in humpback dolphin group sizes were primarily associated with the latitude, sea surface temperature, and abundance. To conclude, our findings provide insights into social dynamics and socioecological trade-offs of humpback dolphins, and help better understand how these resident animals adapted to their shallow-water habitats from the perspectives of biogeography and socioecology.

Comparative genomics of cetartiodactyla: energy metabolism underpins the transition to an aquatic lifestyle.

Foraging disruption caused by human activities is emerging as a key issue in cetacean conservation because it can affect nutrient levels and the amount of energy available to individuals to invest into reproduction. Our ability to predict how anthropogenic stressors affect these ecological processes and ultimately population trajectory depends crucially on our understanding of the complex physiological mechanisms that detect nutrient availability and regulate energy metabolism, foraging behavior and life-history decisions. These physiological mechanisms are likely to differ considerably from terrestrial mammalian model systems. Here, we examine nucleotide substitution rates in cetacean and other artiodactyl genomes to identify signatures of selection in genes associated with nutrient sensing pathways. We also estimated the likely physiological consequences of adaptive amino acid substitutions for pathway functions. Our results highlight that genes involved in the insulin, mTOR and NF-ĸB pathways are subject to significant positive selection in cetaceans compared to terrestrial artiodactyla. These genes may have been positively selected to enable cetaceans to adapt to a glucose-poor diet, to overcome deleterious effects caused by hypoxia during diving (e.g. oxidative stress and inflammation) and to modify fat-depot signaling functions in a manner different to terrestrial mammals. We thus show that adaptation in cetaceans to an aquatic lifestyle significantly affected functions in nutrient sensing pathways. The use of fat stores as a condition index in cetaceans may be confounded by the multiple and critical roles fat has in regulating cetacean metabolism, foraging behavior and diving physiology.

The Effects of Graded Levels of Calorie Restriction: XVI. Metabolomic Changes in the Cerebellum Indicate Activation of Hypothalamocerebellar Connections Driven by Hunger Responses.

Calorie restriction (CR) remains the most robust intervention to extend life span and improve healthspan. Though the cerebellum is more commonly associated with motor control, it has strong links with the hypothalamus and is thought to be associated with nutritional regulation and adiposity. Using a global mass spectrometry-based metabolomics approach, we identified 756 metabolites that were significantly differentially expressed in the cerebellar region of the brain of C57BL/6J mice, fed graded levels of CR (10, 20, 30, and 40 CR) compared to mice fed ad libitum for 12 hours a day. Pathway enrichment indicated changes in the pathways of adenosine and guanine (which are precursors of DNA production), aromatic amino acids (tyrosine, phenylalanine, and tryptophan) and the sulfur-containing amino acid methionine. We also saw increases in the tricarboxylic acid cycle (TCA) cycle, electron donor, and dopamine and histamine pathways. In particular, changes in l-histidine and homocarnosine correlated positively with the level of CR and food anticipatory activity and negatively with insulin and body temperature. Several metabolic and pathway changes acted against changes seen in age-associated neurodegenerative disorders, including increases in the TCA cycle and reduced l-proline. Carnitine metabolites contributed to discrimination between CR groups, which corroborates previous work in the liver and plasma. These results indicate the conservation of certain aspects of metabolism across tissues with CR. Moreover, this is the first study to indicate CR alters the cerebellar metabolome, and does so in a graded fashion, after only a short period of restriction.

The Effects of Graded Levels of Calorie Restriction XV: Phase Space Attractors Reveal Distinct Behavioral Phenotypes.

Calorie restriction (CR) has a positive impact on health and life span. Previous work, however, does not reveal the whole underlying mechanism of behavioral phenotypes under CR. We propose a new approach based on phase space reconstruction (PSR) to analyze the behavioral responses of mice to graded CR. This involved reconstructing high-dimensional attractors which topologically represent the intrinsic dynamics of mice based on low-dimensional time series of movement counts observed during the 90-day time course of restriction. PSR together with correlation dimensions (CD), Kolmogorov entropy (KE), and multifractal spectra builds a map from internal attractors to the phenotype of mice and reveals the mice with increasing CR levels undergo significant changes from a normal to a new state. Features of the attractors (CD and KE) were significantly associated with gene expression profiles in the hypothalamus of the same individuals.

The Effects of Graded Levels of Calorie Restriction: XIV. Global Metabolomics Screen Reveals Brown Adipose Tissue Changes in Amino Acids, Catecholamines, and Antioxidants After Short-Term Restriction in C57BL/6 Mice.

Animals undergoing calorie restriction (CR) often lower their body temperature to conserve energy. Brown adipose tissue (BAT) is stimulated through norepinephrine when rapid heat production is needed, as it is highly metabolically active due to the uncoupling of the electron transport chain from ATP synthesis. To better understand how BAT metabolism changes with CR, we used metabolomics to identify 883 metabolites that were significantly differentially expressed in the BAT of C57BL/6 mice, fed graded CR (10%, 20%, 30%, and 40% CR relative to their individual baseline intake), compared with mice fed ad libitum (AL) for 12 hours a day. Pathway analysis revealed that graded CR had an impact on the TCA cycle and fatty acid degradation. In addition, an increase in nucleic acids and catecholamine pathways was seen with graded CR in the BAT metabolome. We saw increases in antioxidants with CR, suggesting a beneficial effect of mitochondrial uncoupling. Importantly, the instigator of BAT activation, norepinephrine, was increased with CR, whereas its precursors l-tyrosine and dopamine were decreased, indicating a shift of metabolites through the activation pathway. Several of these key changes were correlated with food anticipatory activity and body temperature, indicating BAT activation may be driven by responses to hunger.

The Effects of Graded Levels of Calorie Restriction: XIII. Global Metabolomics Screen Reveals Graded Changes in Circulating Amino Acids, Vitamins, and Bile Acids in the Plasma of C57BL/6 Mice.

Calorie restriction (CR) remains the most robust intervention to extend life span and improve health span. Using a global mass spectrometry-based metabolomics approach, we identified metabolites that were significantly differentially expressed in the plasma of C57BL/6 mice, fed graded levels of calorie restriction (10% CR, 20% CR, 30% CR, and 40% CR) compared with mice fed ad libitum for 12 hours a day. The differential expression of metabolites increased with the severity of CR. Pathway analysis revealed that graded CR had an impact on vitamin E and vitamin B levels, branched chain amino acids, aromatic amino acids, and fatty acid pathways. The majority of amino acids correlated positively with fat-free mass and visceral fat mass, indicating a strong relationship with body composition and vitamin E metabolites correlated with stomach and colon size, which may allude to the beneficial effects of investing in gastrointestinal organs with CR. In addition, metabolites that showed a graded effect, such as the sphinganines, carnitines, and bile acids, match our previous study on liver, which suggests not only that CR remodels the metabolome in a way that promotes energy efficiency, but also that some changes are conserved across tissues.