Long-lived fish has genetic clues to extended lifespan

2021 ◽  
Vol 252 (3361) ◽  
pp. 22
Author(s):  
Aimee Gabay
Keyword(s):  
Extended Lifespan

scholarly journals Intermittent Hypoxia Affects the Spontaneous DifferentiationIn Vitroof Human Neutrophils into Long-Lived Giant Phagocytes

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Larissa Dyugovskaya ◽  
Slava Berger ◽  
Andrey Polyakov ◽  
Peretz Lavie ◽  
Lena Lavie
Keyword(s):  
Nadph Oxidase ◽  
Intermittent Hypoxia ◽  
Oxidase Inhibitor ◽  
Human Neutrophils ◽  
Hypoxic Conditions ◽  
Oxygen Conditions ◽  
Extended Lifespan ◽  
First Time ◽  
Dose Dependent

Previously we identified, for the first time, a new small-size subset of neutrophil-derived giant phagocytes (Gϕ) which spontaneously developin vitrowithout additional growth factors or cytokines. Gϕare CD66b+/CD63+/MPO+/LC3B+and are characterized by extended lifespan, large phagolysosomes, active phagocytosis, and reactive oxygen species (ROS) production, and autophagy largely controls their formation. Hypoxia, and particularly hypoxia/reoxygenation, is a prominent feature of many pathological processes. Herein we investigated Gϕformation by applying various hypoxic conditions. Chronic intermittent hypoxia (IH) (29 cycles/day for 5 days) completely abolished Gϕformation, while acute IH had dose-dependent effects. Exposure to 24 h (56 IH cycles) decreased their size, yield, phagocytic ability, autophagy, mitophagy, and gp91-phox/p22-phoxexpression, whereas under 24 h sustained hypoxia (SH) the size and expression of LC3B and gp91-phox/p22-phoxresembled Gϕformed in normoxia. Diphenyl iodide (DPI), a NADPH oxidase inhibitor, as well as the PI3K/Akt and autophagy inhibitor LY294002 abolished Gϕformation at all oxygen conditions. However, the potent antioxidant, N-acetylcysteine (NAC) abrogated the effects of IH by inducing large CD66b+/LC3B+Gϕand increased both NADPH oxidase expression and phagocytosis. These findings suggest that NADPH oxidase, autophagy, and the PI3K/Akt pathway are involved in Gϕdevelopment.

Anti-aging natural compounds and their role in the regulation of metabolic pathways leading to longevity

2021 ◽  
Vol 21 ◽  
Author(s):  
Aqsa Muzammil ◽  
Muhammad Waqas ◽  
Ahitsham Umar ◽  
Muhammad Sufyan ◽  
Abdur Rehman ◽  
...  
Keyword(s):  
Natural Products ◽  
Metabolic Pathways ◽  
Natural Compounds ◽  
Chronic Obstructive ◽  
Telomere Shortening ◽  
Age Related ◽  
Chronic Obstructive Pulmonary Diseases ◽  
Extended Lifespan ◽  
Ancient Times

: Aging is an unavoidable process, leads to cell senescence due to physiochemical changes in an organism. Anti-aging remedies have always been of great interest since ancient times. The purpose of anti-aging activities is to increase the life span and the quality of life. Anti-aging activities are primarily involved in the therapies of age-related disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), cardiovascular diseases, cancer and chronic obstructive pulmonary diseases. These diseases are triggered by multiple factors that are involved in numerous molecular pathways including telomere shortening, NF-κB pathway, adiponectin receptor pathway, insulin and IGF signaling pathway, AMPK, mTOR and mitochondria dysfunction. Natural products are known as effective molecules to delay the aging process through influencing metabolic pathways and thus ensure an extended lifespan. These natural compounds are being utilized in drug design and development through computational and high throughput techniques for effective pro-longevity drugs. A comprehensive study of natural compounds demonstrated with their anti-aging activities along with databases of natural products for drug designing was executed and summarized in this review article.

scholarly journals Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice

2018 ◽  
Author(s):  
Christine Müller ◽  
Laura M. Zidek ◽  
Tobias Ackermann ◽  
Tristan de Jong ◽  
Peng Liu ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Upstream Open Reading Frame ◽  
Reading Frame ◽  
Physical Decline ◽  
Genetic Ablation ◽  
Mechanistic Target Of Rapamycin ◽  
Age Related ◽  
Extended Lifespan ◽  
Mtorc1 Pathway ◽  
Factor C

AbstractAgeing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBP β ‐LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the C/EBP β-mRNA. Here we describe that reduced C/EBP β ‐LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice. Moreover, female C/EBP βΔuORF mice display an extended lifespan. Since LIP levels increase upon aging in wt mice, our data reveal an important role for C/EBPβ in the aging process and suggest that restriction of LIP expression sustains health and fitness. Thus, therapeutic strategies targeting C/EBP β ‐LIP may offer new possibilities to treat age-related diseases and to prolong healthspan.

scholarly journals E. coli hypoxia-inducible factor ArcA mediates lifespan extension in a lipoic acid synthase mutant by suppressing acetyl-CoA synthetase

2010 ◽  
Vol 391 (10) ◽  
Author(s):  
Stavros Gonidakis ◽  
Steven E. Finkel ◽  
Valter D. Longo
Keyword(s):  
Heat Shock ◽  
Carbon Source ◽  
Pyruvate Dehydrogenase Complex ◽  
Hypoxia Inducible Factor ◽  
Acetyl Coa ◽  
E Coli ◽  
Extended Lifespan ◽  
Shock Resistance ◽  
Survival Extension

Abstract We have previously shown that both the hypoxia-inducible transcription factor ArcA and the PoxB/Acs bypass of the pyruvate dehydrogenase complex contribute to extended lifespan in Escherichia coli. In agreement with studies in higher eukaryotes, we also demonstrated that long-lived E. coli mutants, including LipA-deficient cells, are stress resistant. Here, we show that ArcA contributes to the enhanced lifespan and heat shock resistance of the lipA mutant by suppressing expression of the acetyl-CoA synthetase (acs) gene. The deletion of acs reversed the reduced lifespan of the lipA arcA mutant and promoted the accumulation of extracellular acetate, indicating that inhibition of carbon source uptake contributes to survival extension. However, Acs also sensitized cells lacking ArcA to heat shock, in the absence of extracellular acetate. These results provide evidence for the role of Acs in regulating lifespan and/or stress resistance by both carbon source uptake-dependent and -independent mechanisms.

scholarly journals Longevity of africanized worker honey bees (Apis mellifera) carrying eye color mutant alleles

2003 ◽  
Vol 60 (2) ◽  
pp. 277-281 ◽  
Author(s):  
Rosana de Almeida ◽  
Ademilson Espencer Egea Soares
Keyword(s):  
Apis Mellifera ◽  
Honey Bees ◽  
Statistical Difference ◽  
Close Association ◽  
Control Group ◽  
Brown Pigment ◽  
Eye Color ◽  
Color Mutant ◽  
Extended Lifespan ◽  
Eye Pigmentation

The dark coloration of insects eyes is attributed to the accumulation of the brown pigment insectorubin, a mixture of ommochromes, xanthommatin and several ommins, biosynthesized from tryptophan. When any of the events in the synthesis chain is interrupted, formation and accumulation of pigments other than insectorubin occurs, and a new eye color will appear. The aim of the present work is to evaluate the longevity of worker honey bees Apis mellifera, homozygous and heterozygous for the mutant alleles cream (cr), snow-laranja (s la) and brick (bk). Eye pigmentation and average longetivity of bees are very closely related. Mutant bees carrying lighter eye pigmentation are unable to return to the hive; there is, therefore, a close association between the eye pigmentation and honey bees lifespan. Experiments ran in confinement cages confirm the orientation problems of mutant honey bees, which kept in a limited space, were able to return to the hive and had an extended lifespan in comparison to that observed in the nature, and did not present statistical difference (P>0.05) relative to the control group. Confinement to restricted areas improves honey bees orientation abilities and facilitates return to the hive.

Investigating the Effect of Software Complexity Metrics on Software Cost

2014 ◽  
Vol 548-549 ◽  
pp. 1319-1325
Author(s):  
Bouchaib Falah ◽  
Sara El Alaoui ◽  
Hajar Abbadi
Keyword(s):  
Life Cycle ◽  
Software Engineering ◽  
Software Metrics ◽  
Software Life Cycle ◽  
Software Cost ◽  
Software Complexity ◽  
Complexity Metrics ◽  
Extended Lifespan ◽  
New Methodologies ◽  
Do So

Nowadays, software is expected to have an extended lifespan, which makes the evaluation of its complexity at the early stages critical in upcoming maintenance. Indeed, complexity is proportional to the evolution of software. Software metrics were introduced as tools that allow us to obtain an objective measurement of the complexity of software. Hence, enabling software engineering to assess and manage software complexity. Reducing software costs is one of the major concerns of software engineering which creates an increasing need for new methodologies and techniques to control those costs. Software complexity metrics can help us to do so. In this paper, we would investigate how those metrics can be used to reduce software costs. We would first analyze the most popular complexity metrics and distinguish their properties. Then, we will show how each of those metrics fit within the software life cycle. Finally, we will provide a detailed approach to use the complexity metrics to reduce software costs.

scholarly journals Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett syndrome

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Kerstin Ure ◽  
Hui Lu ◽  
Wei Wang ◽  
Aya Ito-Ishida ◽  
Zhenyu Wu ◽  
...  
Keyword(s):  
Social Skills ◽  
Mouse Model ◽  
Rett Syndrome ◽  
Therapeutic Option ◽  
Neurodevelopmental Disorder ◽  
Gabaergic Neurons ◽  
Inhibitory Neurons ◽  
Extended Lifespan ◽  
Inhibitory Signaling

The postnatal neurodevelopmental disorder Rett syndrome, caused by mutations in MECP2, produces a diverse array of symptoms, including loss of language, motor, and social skills and the development of hand stereotypies, anxiety, tremor, ataxia, respiratory dysrhythmias, and seizures. Surprisingly, despite the diversity of these features, we have found that deleting Mecp2 only from GABAergic inhibitory neurons in mice replicates most of this phenotype. Here we show that genetically restoring Mecp2 expression only in GABAergic neurons of male Mecp2 null mice enhanced inhibitory signaling, extended lifespan, and rescued ataxia, apraxia, and social abnormalities but did not rescue tremor or anxiety. Female Mecp2+/- mice showed a less dramatic but still substantial rescue. These findings highlight the critical regulatory role of GABAergic neurons in certain behaviors and suggest that modulating the excitatory/inhibitory balance through GABAergic neurons could prove a viable therapeutic option in Rett syndrome.

scholarly journals Mid-Gestation lethality of Atxn2l-Ablated Mice

2020 ◽  
Vol 21 (14) ◽  
pp. 5124 ◽  
Author(s):  
Jana Key ◽  
Patrick N. Harter ◽  
Nesli-Ece Sen ◽  
Elise Gradhand ◽  
Georg Auburger ◽  
...  
Keyword(s):  
Giant Cells ◽  
Neural Cells ◽  
Rna Surveillance ◽  
Extended Lifespan ◽  
Ataxin 2 ◽  
Locomotor Deficits ◽  
Lateral Sclerosis

Depletion of yeast/fly Ataxin-2 rescues TDP-43 overexpression toxicity. In mouse models of Amyotrophic Lateral Sclerosis via TDP-43 overexpression, depletion of its ortholog ATXN2 mitigated motor neuron degeneration and extended lifespan from 25 days to >300 days. There is another ortholog in mammals, named ATXN2L (Ataxin-2-like), which is almost uncharacterized but also functions in RNA surveillance at stress granules. We generated mice with Crispr/Cas9-mediated deletion of Atxn2l exons 5-8, studying homozygotes prenatally and heterozygotes during aging. Our novel findings indicate that ATXN2L absence triggers mid-gestational embryonic lethality, affecting female animals more strongly. Weight and development stages of homozygous mutants were reduced. Placenta phenotypes were not apparent, but brain histology showed lamination defects and apoptosis. Aged heterozygotes showed no locomotor deficits or weight loss over 12 months. Null mutants in vivo displayed compensatory efforts to maximize Atxn2l expression, which were prevented upon nutrient abundance in vitro. Mouse embryonal fibroblast cells revealed more multinucleated giant cells upon ATXN2L deficiency. In addition, in human neural cells, transcript levels of ATXN2L were induced upon starvation and glucose and amino acids exposure, but this induction was partially prevented by serum or low cholesterol administration. Neither ATXN2L depletion triggered dysregulation of ATXN2, nor a converse effect was observed. Overall, this essential role of ATXN2L for embryogenesis raises questions about its role in neurodegenerative diseases and neuroprotective therapies.

Sign in / Sign up

Export Citation Format

Share Document