ORCID Profile
0000-0003-2794-0185
Current Organisation
Colorado State University
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Publisher: Informa UK Limited
Date: 09-2017
DOI: 10.2147/CIA.S145247
Publisher: Oxford University Press (OUP)
Date: 24-05-2020
Abstract: Aging is a powerful risk factor for the development of many chronic diseases including dementia. Research based on disease models of dementia have yet to yield effective treatments, therefore it is opportune to consider whether the aging process itself might be a potential therapeutic target for the treatment and prevention of dementia. Numerous cellular and molecular pathways have been implicated in the aging process and compounds that target these processes are being developed to slow aging and delay the onset of age-associated conditions. A few particularly promising therapeutic agents have been shown to influence many of the main hallmarks of aging and increase life span in rodents. Here we discuss the evidence that some of these antiaging compounds may beneficially affect brain aging and thereby lower the risk for dementia.
Publisher: Springer Science and Business Media LLC
Date: 21-07-2020
DOI: 10.1038/S41514-020-0046-6
Abstract: There is an unmet need and urgency to find safe and effective anti-obesity interventions. Our recent study in mice fed on obesogenic diet found that treatment with the alcohol aversive drug disulfiram reduced feeding efficiency and led to a decrease in body weight and an increase in energy expenditure. The intervention with disulfiram improved glucose tolerance and insulin sensitivity, and mitigated metabolic dysfunctions in various organs through poorly defined mechanisms. Here, integrated analysis of transcriptomic and proteomic data from mouse and rat livers unveiled comparable signatures in response to disulfiram, revealing pathways associated with lipid and energy metabolism, redox, and detoxification. In cell culture, disulfiram was found to be a potent activator of autophagy, the malfunctioning of which has negative consequences on metabolic regulation. Thus, repurposing disulfiram may represent a potent strategy to combat obesity.
Publisher: Oxford University Press (OUP)
Date: 21-03-2022
Abstract: Older age is the primary risk factor for most chronic diseases, including Alzheimer’s disease (AD). Current preclinical models to study brain aging and AD are mainly transgenic and harbor mutations intended to mirror brain pathologies associated with human brain aging/AD (eg, by increasing production of the amyloid precursor protein, amyloid beta [Aβ], and/or phosphorylated tau, all of which are key pathological mediators of AD). Although these models may provide insight on pathophysiological processes in AD, none completely recapitulate the disease and its strong age-dependence, and there has been limited success in translating preclinical results and treatments to humans. Here, we describe 2 nontransgenic guinea pig (GP) models, a standard PigmEnTed (PET) strain, and lesser-studied Dunkin-Hartley (DH) strain, that may naturally mimic key features of brain aging and AD in humans. We show that brain aging in PET GP is transcriptomically similar to human brain aging, whereas older DH brains are transcriptomically more similar to human AD. Both strains/models also exhibit increased neurofilament light chain (NFL, a marker of neuronal damage) with aging, and DH animals display greater S100 calcium-binding protein B (S100β), ionized calcium-binding adapter molecule 1 (Iba1), and Aβ and phosphorylated tau—which are all important markers of neuroinflammation-associated AD. Collectively, our results suggest that both the PET and DH GP may be useful, nontransgenic models to study brain aging and AD, respectively.
Publisher: Elsevier BV
Date: 08-2020
Publisher: No publisher found
Date: 2023
DOI: 10.1111/ACEL.13798
Publisher: Elsevier BV
Date: 11-2016
Publisher: Oxford University Press (OUP)
Date: 28-04-2016
Publisher: Microbiology Society
Date: 2021
Abstract: Cryptosporidiosis is a major cause of diarrhoeal illness among African children, and is associated with childhood mortality, malnutrition, cognitive development and growth retardation. Cryptosporidium hominis is the dominant pathogen in Africa, and genotyping at the glycoprotein 60 ( gp60 ) gene has revealed a complex distribution of different subtypes across this continent. However, a comprehensive exploration of the metapopulation structure and evolution based on whole-genome data has yet to be performed. Here, we sequenced and analysed the genomes of 26 C . hominis isolates, representing different gp60 subtypes, collected at rural sites in Gabon, Ghana, Madagascar and Tanzania. Phylogenetic and cluster analyses based on single-nucleotide polymorphisms showed that isolates predominantly clustered by their country of origin, irrespective of their gp60 subtype. We found a significant isolation-by-distance signature that shows the importance of local transmission, but we also detected evidence of hybridization between isolates of different geographical regions. We identified 37 outlier genes with exceptionally high nucleotide ersity, and this group is significantly enriched for genes encoding extracellular proteins and signal peptides. Furthermore, these genes are found more often than expected in recombinant regions, and they show a distinct signature of positive or balancing selection. We conclude that: (1) the metapopulation structure of C. hominis can only be accurately captured by whole-genome analyses (2) local anthroponotic transmission underpins the spread of this pathogen in Africa (3) hybridization occurs between distinct geographical lineages and (4) genetic introgression provides novel substrate for positive or balancing selection in genes involved in host–parasite coevolution.
Publisher: Springer Science and Business Media LLC
Date: 29-04-2019
Publisher: Oxford University Press (OUP)
Date: 23-04-2018
Publisher: Oxford University Press (OUP)
Date: 08-05-2017
Publisher: Cold Spring Harbor Laboratory
Date: 27-06-2020
DOI: 10.1101/2020.06.25.172023
Abstract: Transcripts from non-coding repetitive elements (RE) in the genome may be involved in aging. However, they are often ignored in transcriptome studies on healthspan and lifespan, and their role in healthy aging interventions has not been characterized. Here, we analyze RE in RNA-seq datasets from mice subjected to robust healthspan- and lifespan-increasing interventions including calorie restriction, rapamycin, acarbose, 17-α-estradiol, and Protandim. We also examine RE transcripts in long-lived transgenic mice, and in mice subjected to high-fat diet, and we use RNA-seq to investigate the influence of aerobic exercise on RE transcripts with aging in humans. We find that: 1) healthy aging interventions/behaviors globally reduce RE transcripts, whereas aging and age-accelerating treatments increase RE expression and 2) reduced RE expression with healthy aging interventions is associated with biological hysiological processes mechanistically linked with aging. Thus, RE transcript dysregulation and suppression are likely novel mechanisms underlying aging and healthy aging interventions, respectively.
Publisher: MDPI AG
Date: 24-10-2022
Abstract: Polyphenols are considered vital bioactive compounds beneficial for human health. The Australian flora is enriched with polyphenols which are not fully characterized yet. Thus, the main objective of this study was to identify and characterize the Australian native sandalwood nuts, wattle seeds, lemongrass, and old man saltbush for phenolic compounds and their antioxidant activities. In this study, we tentatively identified a total of 155 phenolic compounds including 25 phenolic acids, 55 flavonoids, 22 isoflavonoids, 22 tannins, 22 lignans, 33 stilbenes, 33 coumarins and derivatives, 12 tyrosols and derivatives, and 6 phenolic terpenes. The highest total phenolic content (TPC) (15.09 ± 0.88 mg GAE/g) was quantified in lemongrass, while the lowest TPC (4.17 ± 0.33 mg GAE/g) was measured in wattle seeds. The highest total flavonoid content (TFC) and total condensed tannins (TCT) were measured in lemongrass and wattle seeds, respectively. A total of 18 phenolic metabolites were quantified/semi-quantified in this experiment. Lemongrass contains a vast number of phenolic metabolites.
Publisher: Wiley
Date: 13-04-2020
DOI: 10.1113/JP278806
Publisher: Elsevier BV
Date: 11-2018
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.NBD.2019.104481
Abstract: Aging is the greatest risk factor for most diseases including cancer, cardiovascular disorders, and neurodegenerative disease. There is emerging evidence that interventions that improve metabolic health with aging may also be effective for brain health. The most robust interventions are non-pharmacological and include limiting calorie or protein intake, increasing aerobic exercise, or environmental enrichment. In humans, dietary patterns including the Mediterranean, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) and Okinawan diets are associated with improved age-related health and may reduce neurodegenerative disease including dementia. Rapamycin, metformin and resveratrol act on nutrient sensing pathways that improve cardiometabolic health and decrease the risk for age-associated disease. There is some evidence that they may reduce the risk for dementia in rodents. There is a growing recognition that improving metabolic function may be an effective way to optimize brain health during aging.
Publisher: Wiley
Date: 05-06-2020
DOI: 10.1111/ACEL.13167
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.CMET.2016.09.001
Abstract: Fibroblast growth factor 21 (FGF21) is the first known endocrine signal activated by protein restriction. Although FGF21 is robustly elevated in low-protein environments, increased FGF21 is also seen in various other contexts such as fasting, overfeeding, ketogenic diets, and high-carbohydrate diets, leaving its nutritional context and physiological role unresolved and controversial. Here, we use the Geometric Framework, a nutritional modeling platform, to help reconcile these apparently conflicting findings in mice confined to one of 25 diets that varied in protein, carbohydrate, and fat content. We show that FGF21 was elevated under low protein intakes and maximally when low protein was coupled with high carbohydrate intakes. Our results explain how elevation of FGF21 occurs both under starvation and hyperphagia, and show that the metabolic outcomes associated with elevated FGF21 depend on the nutritional context, differing according to whether the animal is in a state of under- or overfeeding.
Publisher: Oxford University Press (OUP)
Date: 08-10-2018
Abstract: Macronutrients and dietary energy influence aging, age-related health, and life span. Reduction in telomere length has been proposed as one mechanism for aging. Therefore, this study investigated the effects of varying ratios of dietary macronutrients and energy on telomere length in older adult mice. C57Bl/6 mice were fed ad libitum their entire life on one of 25 diets varying in protein, carbohydrates, fat, and energy. Average telomere length ratio (ATLR) was measured by polymerase chain reaction in livers of a subset of 161 mice aged 15 months. There was a significant positive relationship between ATLR and carbohydrate intake and a negative relationship with protein intake, but no relationships with fat or energy intake. Analysis using the Geometric Framework and Generalized Additive Models confirmed that carbohydrate intake was positively associated with ATLR, while the longest ATLR was achieved by mice restricted to low protein, high carbohydrate diets. ATLR distribution across the diets was parallel to median life-span results previously published. ATLR was associated with blood levels of some amino acids (asparagine, glutamate, taurine) but not with blood levels of fatty acids, hepatic mitochondrial function, or nutrient sensing pathways. In conclusion, mice on low protein, high carbohydrate diets have the longest hepatic telomeres and longest life span.
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 06-2016
Publisher: MDPI AG
Date: 28-10-2022
DOI: 10.3390/NU14214535
Abstract: Calorie restriction (CR), defined as a reduction of the total calorie intake of 30% to 60% without malnutrition, is the only nutritional strategy that has been shown to extend lifespan, prevent or delay the onset of age-associated diseases, and delay the functional decline in a wide range of species. However, little is known about the effects of CR when started early in life. We sought to analyze the effects of CR in the skeletal muscle of young Wistar rats. For this, 3-month-old male and female rats were subjected to 40% CR or fed ad libitum for 3 months. Gastrocnemius muscles were used to extract RNA and total protein. Western blot and RT-qPCR were performed to evaluate the expression of key markers athways modulated by CR and affected by aging. CR decreased body and skeletal muscle weight in both sexes. No differences were found in most senescence, antioxidant, and nutrient sensing pathways analyzed. However, we found a sexual dimorphism in markers of oxidative stress, inflammation, apoptosis, and mitochondrial function in response to CR. Our data show that young female rats treated with CR exhibit similar expression patterns of key genes athways associated with healthy aging when compared to old animals treated with CR, while in male rats these effects are reduced. Additional studies are needed to understand how early or later life CR exerts positive effects on healthspan and lifespan.
Publisher: Elsevier BV
Date: 05-2015
Publisher: Wiley
Date: 29-03-2019
Publisher: Frontiers Media SA
Date: 23-04-2014
No related grants have been discovered for Devin Wahl.