Trade-Offs Between Hepatic Host Defense and Metabolic Programs Underlie Sex-Biased Diseases

Current concepts in evolutionary medicine propose that trade-offs and mismatches with a shifting environment increase disease risk. While biological sex also impacts disease prevalence, contributions of environmental pressures to sex-biased diseases remain unexplored. Here, we show that sex-dependent hepatic programs confer a robust (~300%) survival advantage for male mice during lethal bacterial infection. The transcription factor BCL6, which masculinizes hepatic gene expression at puberty, is essential for this advantage. However, protection by BCL6 comes at a cost following dietary excess, resulting in overt fatty liver and glucose intolerance in males. Deleting hepatic BCL6 reverses these phenotypes but markedly lowers male fitness during infection, thus establishing a sex-dependent tradeoff between host defense and metabolic systems. We suggest that these tradeoffs, coupled with current environmental pressures, drive metabolic disease in males.

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Implementing Cardiorespiratory Fitness as a Routine Measure in Health Care Settings

Journal of Clinical Exercise Physiology ◽

10.31189/2165-6193-10.2.62 ◽

2021 ◽

Vol 10 (2) ◽

pp. 62-69

Author(s):

Jonathan Myers ◽

Robert Ross

Keyword(s):

Health Care ◽

Cardiorespiratory Fitness ◽

Exercise Test ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Maximal Exercise Test ◽

Health Care Settings ◽

Biological Sex ◽

Clinical Encounters ◽

Routine Measure

ABSTRACT It is well established that cardiorespiratory fitness (CRF) is inversely associated with numerous morbidities independent of age, biological sex, race or ethnicity, and commonly obtained risk factors. More recent evidence also demonstrates that the addition of CRF to multivariable risk prediction algorithms used to estimate cardiovascular disease risk improves risk stratification. However, it is neither feasible nor appropriate to perform an exercise test to quantify CRF during most routine clinical encounters. A growing number of studies have suggested that CRF can be assessed pragmatically and reasonably accurately without performing a maximal exercise test. The concept that CRF can be substantially improved in response to regular exercise consistent with consensus recommendations underscores the recommendation that CRF should be a routine measure—a vital sign—across health care settings. Herein, we provide a brief, narrative overview of the evidence in support of this recommendation.

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Computational framework for evaluating risk trade-offs in costs associated with Legionnaires’ Disease risk, energy, and scalding risk for hospital hot water systems

Environmental Science Water Research & Technology ◽

10.1039/d1ew00397f ◽

2021 ◽

Author(s):

Ashley Heida ◽

Alexis Mraz ◽

Mark Hamilton ◽

Mark Weir ◽

Kerry A Hamilton

Keyword(s):

Legionella Pneumophila ◽

Disease Risk ◽

Disease Outbreaks ◽

Febrile Illness ◽

Water Systems ◽

Hot Water ◽

Computational Framework ◽

Trade Offs ◽

Pontiac Fever ◽

Legionnaires Disease

Legionella pneumophila are bacteria that when inhaled cause Legionnaires’ Disease (LD) and febrile illness Pontiac Fever. As of 2014, LD is the most frequent cause of waterborne disease outbreaks due...

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CONVERGENT AGING LOCI: PATHWAYS THAT TRANSCEND INDIVIDUAL DISEASES

Innovation in Aging ◽

10.1093/geroni/igz038.810 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S221-S221

Author(s):

Luke C Pilling ◽

Luigi Ferrucci ◽

David Melzer

Keyword(s):

Disease Risk ◽

Association Studies ◽

Genome Wide Association Studies ◽

Telomere Shortening ◽

Chronic Disease Risk ◽

Trade Offs ◽

Age Related ◽

Genome Wide ◽

Artery Disease

Abstract Thousands of loci across the genome have been identified for specific diseases in genome-wide association studies (GWAS), yet very few are associated with lifespan itself. We hypothesized that specific biological pathways transcend individual diseases and affect health and lifespan more broadly. Using the published results for the most recent GWAS for 10 key age-related diseases (including coronary artery disease, type-2 diabetes, and several cancers) we identified 22 loci with a strong genetic association with at least three of the diseases. These multi-trait aging loci include known genes affecting multiple diverse health end points, such as CDKN2A/B (9p21.3) and APOE. There are also novel multi-trait genes including SH2B3 and CASC8, likely involved in hallmark pathways of aging biology, including telomere shortening and inflammation. Several of these loci involve trade-offs between chronic disease risk and cancer.

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Relationship between chronic kidney disease prevalence and end-stage renal disease risk

Current Opinion in Nephrology & Hypertension ◽

10.1097/mnh.0b013e3282f8b177 ◽

2008 ◽

Vol 17 (3) ◽

pp. 286-291 ◽

Cited By ~ 25

Author(s):

Stein Ivar Hallan ◽

Bjørn Egil Vikse

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Disease ◽

End Stage Renal Disease ◽

Disease Risk ◽

Disease Prevalence ◽

Chronic Kidney Disease Prevalence ◽

Stage Renal Disease ◽

End Stage

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An evolutionary medicine perspective on pain and its disorders

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0288 ◽

2019 ◽

Vol 374 (1785) ◽

pp. 20190288 ◽

Cited By ~ 4

Author(s):

Randolph M. Nesse ◽

Jay Schulkin

Keyword(s):

Chronic Pain ◽

Tissue Damage ◽

Mental States ◽

Preliminary Evidence ◽

Evolutionary Medicine ◽

Smoke Detector ◽

Pain Mechanisms ◽

Trade Offs ◽

Pathological Pain ◽

The Cost

Enormous progress in understanding the mechanisms that mediate pain can be augmented by an evolutionary medicine perspective on how the capacity for pain gives selective advantages, the trade-offs that shaped the mechanisms, and evolutionary explanations for the system's vulnerability to excessive and chronic pain. Syndromes of deficient pain document tragically the utility of pain to motivate escape from and avoidance of situations causing tissue damage. Much apparently excessive pain is actually normal because the cost of more pain is often vastly less than the cost of too little pain (the smoke detector principle). Vulnerability to pathological pain may be explained in part because natural selection has shaped mechanisms that respond adaptively to repeated tissue damage by decreasing the pain threshold and increasing pain salience. The other half of an evolutionary approach describes the phylogeny of pain mechanisms; the apparent independence of different kinds of pain is of special interest. Painful mental states such as anxiety, guilt and low mood may have evolved from physical pain precursors. Preliminary evidence for this is found in anatomic and genetic data. Such insights from evolutionary medicine may help in understanding vulnerability to chronic pain. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

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Effects of parasite pressure on parasite mortality and reproductive output in a rodent-flea system: inferring host defense trade-offs

Parasitology Research ◽

10.1007/s00436-016-5093-3 ◽

2016 ◽

Vol 115 (9) ◽

pp. 3337-3344 ◽

Cited By ~ 2

Author(s):

Elizabeth M. Warburton ◽

Michael Kam ◽

Enav Bar-Shira ◽

Aharon Friedman ◽

Irina S. Khokhlova ◽

...

Keyword(s):

Host Defense ◽

Reproductive Output ◽

Trade Offs

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Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

Journal of The Royal Society Interface ◽

10.1098/rsif.2015.1046 ◽

2016 ◽

Vol 13 (117) ◽

pp. 20151046 ◽

Cited By ~ 31

Author(s):

Fei He ◽

Ettore Murabito ◽

Hans V. Westerhoff

Keyword(s):

Systems Biology ◽

Synthetic Biology ◽

Regulatory Networks ◽

Computational Systems Biology ◽

Control Engineering ◽

Trade Offs ◽

Metabolic Systems ◽

Analytical Approaches

Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo , not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways.

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Effects of host extinction and vector preferences on vector-borne disease risk in phylogenetically structured host-hector communities

PLoS ONE ◽

10.1371/journal.pone.0256456 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0256456

Author(s):

Charles L. Nunn ◽

Alexander Q. Vining ◽

Debapriyo Chakraborty ◽

Michael H. Reiskind ◽

Hillary S. Young

Keyword(s):

Host Specificity ◽

Disease Transmission ◽

Species Interactions ◽

Disease Risk ◽

Structural Characteristics ◽

Phylogenetic Signal ◽

Disease Prevalence ◽

Species Loss ◽

Ecological Communities ◽

Threat Status

Anthropogenic disturbance impacts the phylogenetic composition and diversity of ecological communities. While changes in diversity are known to dramatically change species interactions and alter disease dynamics, the effects of phylogenetic changes in host and vector communities on disease have been relatively poorly studied. Using a theoretical model, we investigated how phylogeny and extinction influence network structural characteristics relevant to disease transmission in disturbed environments. We modelled a multi-host, multi-vector community as a bipartite ecological network, where nodes represent host and vector species and edges represent connections among them through vector feeding, and we simulated vector preferences and threat status on host and parasite phylogenies. We then simulated loss of hosts, including phylogenetically clustered losses, to investigate how extinction influences network structure. We compared effects of phylogeny and extinction to those of host specificity, which we predicted to strongly increase network modularity and reduce disease prevalence. The simulations revealed that extinction often increased modularity, with higher modularity as species loss increased, although not as much as increasing host specificity did. These results suggest that extinction itself, all else being equal, may reduce disease prevalence in disturbed communities. However, in real communities, systematic patterns in species loss (e.g. favoring high competence species) or changes in abundance may counteract these effects. Unexpectedly, we found that effects of phylogenetic signal in host and vector traits were relatively weak, and only important when phylogenetic signal of host and vector traits were similar, or when these traits both varied.

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Metabolic programming in early life in humans

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2018.0123 ◽

2019 ◽

Vol 374 (1770) ◽

pp. 20180123 ◽

Cited By ~ 16

Author(s):

Caroline H. D. Fall ◽

Kalyanaraman Kumaran

Keyword(s):

Metabolic Disease ◽

Birth Weight ◽

Early Life ◽

Disease Risk ◽

Evolutionary Medicine ◽

Metabolic Effects ◽

High Birth Weight ◽

Preventive Strategy ◽

Increased Risk

An association of low birth weight with an increased risk of adult cardiovascular disease and diabetes led to the developmental origins of health and disease (DOHaD) hypothesis, which proposes that undernutrition during early development permanently ‘programmes’ organ structure and metabolism, leading to vulnerability to later cardio-metabolic disease. High birth weight caused by maternal gestational diabetes is also associated with later diabetes, suggesting that fetal over-nutrition also has programming effects. Post-natal factors (excess weight gain/obesity, smoking, poor diets and physical inactivity) interact with fetal exposures to increase disease risk. Animal studies have shown permanent metabolic effects in offspring after alterations to maternal or early post-natal diets but evidence in humans is largely limited to observational and quasi-experimental situations such as maternal famine exposure. Randomized trials of maternal nutritional interventions during pregnancy have so far had limited follow-up of the offspring. Moreover, interventions usually started after the first trimester and therefore missed key peri-conceptional or early pregnancy events such as epigenetic changes, placentation and fetal organogenesis. Recent and ongoing trials intervening pre-conceptionally and powered for long-term offspring follow-up will address these issues. While current preventive strategies for cardio-metabolic disease focus on high-risk individuals in mid-life, DOHaD concepts offer a ‘primordial’ preventive strategy to reduce disease in future generations by improving fetal and infant development. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

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