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

2018 ◽  
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.

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

2016 ◽  
Vol 12 (8) ◽  
pp. 20160243 ◽  
Author(s):  
Charlotte Récapet ◽  
Adélaïde Sibeaux ◽  
Laure Cauchard ◽  
Blandine Doligez ◽  
Pierre Bize
Keyword(s):  
Glycated Haemoglobin ◽  
Protein Glycation ◽  
Model Organisms ◽  
Laboratory Model ◽  
Lower Probability ◽  
Poor Control ◽  
Free Living ◽  
Glucose Homoeostasis ◽  
Age Related ◽  
Individual Probability

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.

scholarly journals StimulatingS-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK

2016 ◽  
Vol 113 (42) ◽  
pp. 11913-11918 ◽  
Author(s):  
Takafumi Ogawa ◽  
Ryohei Tsubakiyama ◽  
Muneyoshi Kanai ◽  
Tetsuya Koyama ◽  
Tsutomu Fujii ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Cell Survival ◽  
Metabolic Effects ◽  
Model Organisms ◽  
Lifespan Extension ◽  
Beneficial Effects ◽  
Energy Sensing ◽  
Amp Activated Protein Kinase ◽  
Methionine Synthesis

Dietary restriction (DR), such as calorie restriction (CR) or methionine (Met) restriction, extends the lifespan of diverse model organisms. Although studies have identified several metabolites that contribute to the beneficial effects of DR, the molecular mechanism underlying the key metabolites responsible for DR regimens is not fully understood. Here we show that stimulatingS-adenosyl-l-methionine (AdoMet) synthesis extended the lifespan of the budding yeastSaccharomyces cerevisiae. The AdoMet synthesis-mediated beneficial metabolic effects, which resulted from consuming both Met and ATP, mimicked CR. Indeed, stimulating AdoMet synthesis activated the universal energy-sensing regulator Snf1, which is theS. cerevisiaeortholog of AMP-activated protein kinase (AMPK), resulting in lifespan extension. Furthermore, our findings revealed thatS-adenosyl-l-homocysteine contributed to longevity with a higher accumulation of AdoMet only under the severe CR (0.05% glucose) conditions. Thus, our data uncovered molecular links between Met metabolites and lifespan, suggesting a unique function of AdoMet as a reservoir of Met and ATP for cell survival.

scholarly journals Identification of longevity compounds with minimized probabilities of side effects

2020 ◽  
Vol 21 (6) ◽  
pp. 709-719 ◽  
Author(s):  
Georges E. Janssens ◽  
Riekelt H. Houtkooper
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Side Effect ◽  
Aging Population ◽  
Model Organisms ◽  
Lifespan Extension ◽  
Clinical Testing ◽  
Healthy Individuals ◽  
Maximum Lifespan ◽  
Age Related

Abstract It is hypothesized that treating the general aging population with compounds that slow aging, geroprotectors, could provide many benefits to society, including a reduction of age-related diseases. It is intuitive that such compounds should cause minimal side effects, since they would be distributed to otherwise healthy individuals for extended periods of time. The question therefore emerges of how we should prioritize geroprotectors discovered in model organisms for clinical testing in humans. In other words, which compounds are least likely to cause harm, while still potentially providing benefit? To systematically answer this question we queried the DrugAge database—containing hundreds of known geroprotectors—and cross-referenced this with a recently published repository of compound side effect predictions. In total, 124 geroprotectors were associated to 800 unique side effects. Geroprotectors with high risks of side effects, some even with risk for death, included lamotrigine and minocycline, while compounds with low side effect risks included spermidine and d-glucosamine. Despite their popularity as top geroprotector candidates for humans, sirolimus and metformin harbored greater risks of side effects than many other candidate geroprotectors, sirolimus being the more severe of the two. Furthermore, we found that a correlation existed between maximum lifespan extension in worms and the likelihood of causing a side effect, suggesting that extreme lifespan extension in model organisms should not necessarily be the priority when screening for novel geroprotectors. We discuss the implications of our findings for prioritizing geroprotectors, suggesting spermidine and d-glucosamine for clinical trials in humans.

scholarly journals The new biology of ageing

2010 ◽  
Vol 365 (1537) ◽  
pp. 147-154 ◽  
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.

scholarly journals Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo
Keyword(s):  
Oxidative Stress ◽  
Food Sources ◽  
Preventive Action ◽  
Nutritional Interventions ◽  
Beneficial Effects ◽  
Age Related ◽  
Macromolecular Damage ◽  
And Oxidative Stress

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

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

Biomolecules ◽  
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.

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

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.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

scholarly journals Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

2014 ◽  
pp. 309 ◽  
Author(s):  
Cristovam Picanço-Diniz ◽  
Thais Cristina Galdino De Oliveira ◽  
Fernanda Cabral Soares ◽  
Liliane Dias E Dias De Macedo ◽  
Domingos Luiz Wanderley Picanco Diniz ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Long Term Care ◽  
Cognitive Stimulation ◽  
Term Care ◽  
Beneficial Effects ◽  
Age Related ◽  
Age Related Cognitive Decline

scholarly journals Comparing the Protective Value of Human and Pet Social Support on Well-Being of Older Adults During COVID-19

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 936-936
Author(s):  
Juliet Sobering ◽  
Lisa Brown
Keyword(s):  
Social Support ◽  
Older Adults ◽  
Positive Emotions ◽  
Protective Factor ◽  
Behavioral Activation ◽  
Well Being ◽  
Psychological Benefits ◽  
Beneficial Effects ◽  
Age Related ◽  
Media Reports

Abstract Older adults are vulnerable to particular risk factors that contribute to lower well-being and poorer functioning. With the COVID-19 pandemic, the importance of social support has been highlighted in media reports because of its well-known beneficial effects on overall well-being. However, as adults age, social networks, contacts, and activities naturally decrease. These age-related losses are often difficult, if not impossible, to replace. Pets have recently been recognized as a valuable source of social support for many older adults, providing both physical and psychological benefits through mutual connection and behavioral activation. Previous studies have examined how human social support or pet social support enhance older adults’ well-being (i.e., positive emotions, engagement, relationships, accomplishment, and meaning). However, there is a gap in our scientific knowledge as previous research has not evaluated if pet social support can serve as a protective factor in the absence of adequate human social support. Current analyses, with 141 older adult participants, suggests that pet owners with a positive attachment to their pet experience higher well-being as pets serve as a coping resource that protects against common life stressors. Similar to human social support, pet social support appears to be a protective factor that also promotes and fosters a sense of well-being in older adults. Support in late life is especially important for families and agencies to be attuned to, especially during a global pandemic.

Sign in / Sign up

Export Citation Format

Share Document