Selective disappearance of individuals with high levels of glycated haemoglobin in a free-living bird

Although disruption of glucose homeostasis is a hallmark of ageing in humans and laboratory model organisms, we have little information on the importance of this process in free-living animals. Poor control of blood glucose levels leads to irreversible protein glycation. Hence, levels of protein glycation are hypothesized to increase with age and to be associated with a decline in survival. We tested these predictions by measuring blood glycated haemoglobin in 274 adult collared flycatchers of known age and estimating individual probability of recapture in the following 2 years. Results show a strong decrease in glycated haemoglobin from age 1 to 5 years and an increase thereafter. Individuals with high levels of glycated haemoglobin had a lower probability of recapture, even after controlling for effects of age and dispersal. Altogether, our findings suggest that poor control of glucose homoeostasis is associated with lower survival in this free-living bird population, and that the selective disappearance of individuals with the highest glycation levels could account for the counterintuitive age-related decline in glycated haemoglobin in the early age categories.

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Ras inhibition by trametinib treatment in Drosophila attenuates gut pathology in females and extends lifespan in both sexes

10.1101/356295 ◽

2018 ◽

Cited By ~ 1

Author(s):

Jennifer C Regan ◽

Yu-Xuan Lu ◽

Ekin Bolukbasi ◽

Mobina Khericha ◽

Linda Partridge

Keyword(s):

Mek Inhibitor ◽

Model Organisms ◽

Laboratory Model ◽

Lifespan Extension ◽

Parallel Mechanisms ◽

Beneficial Effects ◽

Age Related ◽

Ras Inhibition ◽

Female Specific ◽

Female Lifespan

AbstractFemales of most species live longer than do males. Furthermore, lifespan-extending interventions in laboratory model organisms are often more effective in females (Regan and Partridge 2013). For instance, genetic and pharmacological suppression of activity of the insulin/insulin-like signalling - target of rapamycin (IIS-TOR) network generally extends female lifespan more than that of males in both Drosophila and mice (Clancy et al. 2001; Selman et al. 2009). We previously showed that attenuation of Ras-dependent IIS signalling by treatment with the FDA-approved MEK inhibitor, trametinib extends lifespan in females (Slack et al. 2015). Here, we demonstrate that trametinib treatment has beneficial effects on female-specific, age-related gut pathologies, similar to those obtained through dietary restriction (Regan et al. 2016). Importantly, we identify Ras inhibition as an effective lifespan-extending manipulation in males as well as females, pointing to parallel mechanisms of lifespan extension by trametinib in both sexes.

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The new biology of ageing

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2009.0222 ◽

2010 ◽

Vol 365 (1537) ◽

pp. 147-154 ◽

Cited By ~ 93

Author(s):

Linda Partridge

Keyword(s):

Human Life ◽

Developed Countries ◽

Model Organisms ◽

Laboratory Model ◽

Loss Of Function ◽

Medical Treatments ◽

Age Related ◽

Complex Process ◽

New Findings ◽

Clinical Thinking

Human life expectancy in developed countries has increased steadily for over 150 years, through improvements in public health and lifestyle. More people are hence living long enough to suffer age-related loss of function and disease, and there is a need to improve the health of older people. Ageing is a complex process of damage accumulation, and has been viewed as experimentally and medically intractable. This view has been reinforced by the realization that ageing is a disadvantageous trait that evolves as a side effect of mutation accumulation or a benefit to the young, because of the decline in the force of natural selection at later ages. However, important recent discoveries are that mutations in single genes can extend lifespan of laboratory model organisms and that the mechanisms involved are conserved across large evolutionary distances, including to mammals. These mutations keep the animals functional and pathology-free to later ages, and they can protect against specific ageing-related diseases, including neurodegenerative disease and cancer. Preliminary indications suggest that these new findings from the laboratory may well also apply to humans. Translating these discoveries into medical treatments poses new challenges, including changing clinical thinking towards broad-spectrum, preventative medicine and finding novel routes to drug development.

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Cyclodextrins, Natural Compounds, and Plant Bioactives—A Nutritional Perspective

Biomolecules ◽

10.3390/biom11030401 ◽

2021 ◽

Vol 11 (3) ◽

pp. 401

Author(s):

Svenja Wüpper ◽

Kai Lüersen ◽

Gerald Rimbach

Keyword(s):

Intestinal Flora ◽

Aqueous Solubility ◽

Outer Wall ◽

Natural Compounds ◽

Model Organisms ◽

Laboratory Model ◽

Internal Cavity ◽

Pentacyclic Triterpenoids ◽

Starch Derivatives ◽

Improved Stability

Cyclodextrins (CDs) are a group of cyclic oligosaccharides produced from starch or starch derivatives. They contain six (αCD), seven (βCD), eight (γCD), or more glucopyranose monomers linked via α-1,4-glycosidic bonds. CDs have a truncated cone shape with a hydrophilic outer wall and a less hydrophilic inner wall, the latter forming a more apolar internal cavity. Because of this special architecture, CDs are soluble in water and can simultaneously host lipophilic guest molecules. The major advantage of inclusion into CDs is increased aqueous solubility of such lipophilic substances. Accordingly, we present studies where the complexation of natural compounds such as propolis and dietary plant bioactives (e.g., tocotrienol, pentacyclic triterpenoids, curcumin) with γCD resulted in improved stability, bioavailability, and bioactivity in various laboratory model organisms and in humans. We also address safety aspects that may arise from increased bioavailability of plant extracts or natural compounds owing to CD complexation. When orally administered, α- and βCD—which are inert to intestinal digestion—are fermented by the human intestinal flora, while γCD is almost completely degraded to glucose units by α-amylase. Hence, recent reports indicate that empty γCD supplementation exhibits metabolic activity on its own, which may provide opportunities for new applications.

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Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia

Communications Biology ◽

10.1038/s42003-021-01723-z ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Anastasiya Börsch ◽

Daniel J. Ham ◽

Nitish Mittal ◽

Lionel A. Tintignac ◽

Eugenia Migliavacca ◽

...

Keyword(s):

Muscle Mass ◽

Inflammatory Responses ◽

Molecular Data ◽

Model Organisms ◽

Sequencing Data ◽

Phenotypic Analysis ◽

Age Related ◽

Analogous Data ◽

Species Specific ◽

And Function

AbstractSarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.

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Nanoceria Prevents Glucose-Induced Protein Glycation in Eye Lens Cells

Nanomaterials ◽

10.3390/nano11061473 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1473

Author(s):

Belal I. Hanafy ◽

Gareth W. V. Cave ◽

Yvonne Barnett ◽

Barbara K. Pierscionek

Keyword(s):

Protein Glycation ◽

Human Lens ◽

Lens Epithelial Cells ◽

Oxide Nanoparticles ◽

Lens Protein ◽

Oxygen Species ◽

Human Lens Epithelial Cells ◽

Age Related ◽

Age Related Changes

Cerium oxide nanoparticles (nanoceria) are generally known for their recyclable antioxidative properties making them an appealing biomaterial for protecting against physiological and pathological age-related changes that are caused by reactive oxygen species (ROS). Cataract is one such pathology that has been associated with oxidation and glycation of the lens proteins (crystallins) leading to aggregation and opacification. A novel coated nanoceria formulation has been previously shown to enter the human lens epithelial cells (HLECs) and protect them from oxidative stress induced by hydrogen peroxide (H2O2). In this work, the mechanism of nanoceria uptake in HLECs is studied and multiple anti-cataractogenic properties are assessed in vitro. Our results show that the nanoceria provide multiple beneficial actions to delay cataract progression by (1) acting as a catalase mimetic in cells with inhibited catalase, (2) improving reduced to oxidised glutathione ratio (GSH/GSSG) in HLECs, and (3) inhibiting the non-enzymatic glucose-induced glycation of the chaperone lens protein α-crystallin. Given the multifactorial nature of cataract progression, the varied actions of nanoceria render them promising candidates for potential non-surgical therapeutic treatment.

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The serotonin transporter gene and female personality variation in a free-living passerine

Scientific Reports ◽

10.1038/s41598-021-88225-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Bert Thys ◽

Andrea S. Grunst ◽

Nicky Staes ◽

Rianne Pinxten ◽

Marcel Eens ◽

...

Keyword(s):

Serotonin Transporter ◽

Strong Support ◽

Serotonin Transporter Gene ◽

Female Aggression ◽

Nucleotide Polymorphisms ◽

Transporter Gene ◽

Evolutionary Potential ◽

Free Living ◽

Age Related ◽

Age Dependent

AbstractQuantifying variation in behaviour-related genes provides insight into the evolutionary potential of repeatable among-individual variation in behaviour (i.e. personality). Yet, individuals typically also plastically adjust their behaviour in response to environmental conditions and/or age, thereby complicating the detection of genotype–phenotype associations. Here, using a population of free-living great tits (Parus major), we assessed the association between single nucleotide polymorphisms (SNPs) in the serotonin transporter gene (SERT) and two repeatable behavioural traits, i.e. female-female aggression and female hissing behaviour. For female-female aggression, a trait showing age-related plasticity, we found no evidence for associations with SERT SNPs, even when assessing potential age-dependent effects of SERT genotype on aggression. We also found no strong support for associations between SERT SNPs and hissing behaviour, yet we identified two synonymous polymorphisms (exon 13 SNP66 and exon 12 SNP144) of particular interest, each explaining about 1.3% of the total variation in hissing behaviour. Overall, our results contribute to the general understanding of the biological underpinning of complex behavioural traits and will facilitate further (meta-analytic) research on behaviour-related genes. Moreover, we emphasize that future molecular genetic studies should consider age-dependent genotype–phenotype associations for behavioural trait (co)variation, as this will vastly improve our understanding of the proximate causes and ultimate consequences of personality variation in natural populations.

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Abstract 426: Laminin Downregulation Facilitates Cardiomyocyte Coupling in situ to Increase Contractile Function

Circulation Research ◽

10.1161/res.119.suppl_1.426 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Ayla Sessions ◽

Gaurav Kaushik ◽

Adam Engler

Keyword(s):

Basement Membrane ◽

Contractile Function ◽

Current Model ◽

Model Systems ◽

Model Organisms ◽

Muscle Physiology ◽

Heart Tube ◽

Age Related ◽

New Evidence

Aging is associated with extensive remodeling of the heart, including basement membrane extracellular matrix (ECM) components that surround cardiomyocytes. Remodeling is thought to contribute to impaired cardiac mechanotransduction, but the contribution of specific basement membrane ECM components to age-related cardiac remodeling is unclear, owing to current model systems being complex and slow to age. To investigate the effect of basement membrane remodeling on mechanical function in genetically tractable, rapidly aging, and simple model organisms, we employed Drosophila melanogaster, which has a simple trilayered heart tube composed of only basement membrane ECM. We observed differential regulation of collagens between laboratory Drosophila strains , i.e. yellow-white ( yw ) and white-1118 ( w 1118 ), leading to changes in muscle physiology, which were linked to severity of dysfunction with age. Therefore, we sought to understand the extent to which basement membrane ECM modulates lateral cardiomyocyte coupling and contractile function during aging. Cardiac-restricted knockdown of ECM genes Pericardin , Laminin A , and Viking in Drosophila prevented age-associated heart tube restriction and increased contractility, even under viscous load. Most notably, reduction of Laminin A expression decreased levels of other genes that co-assemble in ECM, leading to overall preservation of contractile velocity and extension of median organismal lifespan by 3 weeks or 39%. These data provide new evidence of a direct link between basement membrane ECM homeostasis, contractility, and maintenance of lifespan.

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Reexamination of Accelerometer Calibration with Energy Expenditure as Criterion: VO2net Instead of MET for Age-Equivalent Physical Activity Intensity

Sensors ◽

10.3390/s19153377 ◽

2019 ◽

Vol 19 (15) ◽

pp. 3377 ◽

Cited By ~ 3

Author(s):

Daniel Arvidsson ◽

Jonatan Fridolfsson ◽

Christoph Buck ◽

Örjan Ekblom ◽

Elin Ekblom-Bak ◽

...

Keyword(s):

Physical Activity ◽

Age Groups ◽

Accelerometer Data ◽

Physical Activity Intensity ◽

Free Living ◽

Activity Intensity ◽

Age Related ◽

Younger Age ◽

Metabolic Equivalent Of Task ◽

Adolescents And Adults

Accelerometer calibration for physical activity (PA) intensity is commonly performed using Metabolic Equivalent of Task (MET) as criterion. However, MET is not an age-equivalent measure of PA intensity, which limits the use of MET-calibrated accelerometers for age-related PA investigations. We investigated calibration using VO2net (VO2gross − VO2stand; mL⋅min−1⋅kg−1) as criterion compared to MET (VO2gross/VO2rest) and the effect on assessment of free-living PA in children, adolescents and adults. Oxygen consumption and hip/thigh accelerometer data were collected during rest, stand and treadmill walk and run. Equivalent speed (Speedeq) was used as indicator of the absolute speed (Speedabs) performed with the same effort in individuals of different body size/age. The results showed that VO2net was higher in younger age-groups for Speedabs, but was similar in the three age-groups for Speedeq. MET was lower in younger age-groups for both Speedabs and Speedeq. The same VO2net-values respective MET-values were applied to all age-groups to develop accelerometer PA intensity cut-points. Free-living moderate-and-vigorous PA was 216, 115, 74 and 71 min/d in children, adolescents, younger and older adults with VO2net-calibration, but 140, 83, 74 and 41 min/d with MET-calibration, respectively. In conclusion, VO2net calibration of accelerometers may provide age-equivalent measures of PA intensity/effort for more accurate age-related investigations of PA in epidemiological research.

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Demography, life-history trade-offs, and the gastrointestinal virome of wild chimpanzees

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0613 ◽

2020 ◽

Vol 375 (1811) ◽

pp. 20190613

Author(s):

Jacob D. Negrey ◽

Melissa Emery Thompson ◽

Kevin E. Langergraber ◽

Zarin P. Machanda ◽

John C. Mitani ◽

...

Keyword(s):

Viral Infection ◽

Rna Virus ◽

Free Living ◽

Trade Offs ◽

Age Related ◽

Viral Communities ◽

Males And Females ◽

Delayed Consequences ◽

Sexually Mature ◽

Older Males

In humans, senescence increases susceptibility to viral infection. However, comparative data on viral infection in free-living non-human primates—even in our closest living relatives, chimpanzees and bonobos ( Pan troglodytes and P. paniscus )—are relatively scarce, thereby constraining an evolutionary understanding of age-related patterns of viral infection. We investigated a population of wild eastern chimpanzees ( P. t. schweinfurthii ), using metagenomics to characterize viromes (full viral communities) in the faeces of 42 sexually mature chimpanzees (22 males, 20 females) from the Kanyawara and Ngogo communities of Kibale National Park, Uganda. We identified 12 viruses from at least four viral families possessing genomes of both single-stranded RNA and single-stranded DNA. Faecal viromes of both sexes varied with chimpanzee age, but viral richness increased with age only in males. This effect was largely due to three viruses, salivirus, porprismacovirus and chimpanzee stool-associated RNA virus (chisavirus), which occurred most frequently in samples from older males. This finding is consistent with the hypothesis that selection on males for early-life reproduction compromises investment in somatic maintenance, which has delayed consequences for health later in life, in this case reflected in viral infection and/or shedding. Faecal viromes are therefore useful for studying processes related to the divergent reproductive strategies of males and females, ageing, and sex differences in longevity. This article is part of the theme issue ‘Evolution of the primate ageing process'.

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Unraveling the mode of action of medicinal plants in delaying age-related diseases using model organisms

Medicinal and Aromatic Plants ◽

10.1016/b978-0-12-819590-1.00002-1 ◽

2021 ◽

pp. 37-60

Author(s):

Mani Iyer Prasanth ◽

Bhagavathi Sundaram Sivamaruthi ◽

Periyanaina Kesika ◽

Pulikkottil Stanes Rosmol ◽

Tewin Tencomnao

Keyword(s):

Medicinal Plants ◽

Mode Of Action ◽

Model Organisms ◽

Age Related

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