LipidClock: A Lipid-Based Predictor of Biological Age.

Complexity is a fundamental feature of biological systems. Omics techniques like lipidomics can simultaneously quantify many thousands of molecules, thereby directly capturing the underlying biological complexity. However, this approach transfers the original biological complexity to the resulting datasets, posing challenges in data reduction and analysis.

Glutathione catabolism by Enterobacteriaceae species to hydrogen sulphide adversely affects the viability of host systems in the presence of 5'fluorodeoxyuridine.

Reduced glutathione (GSH) plays an essential role in relieving oxidative insult from the generation of free radicals via normal physiological processes. However, GSH can be exploited by bacteria as a signalling molecule for the regulation of virulence. We describe findings arising from a serendipitous observation that when GSH and Escherichia coli were incubated with 5'fluorodeoxyuridine (FUdR)-synchronised populations of Caenorhabditis elegans, the nematodes underwent rapid death.

Optogenetic approaches for understanding homeostatic and degenerative processes in Drosophila.

Many organs and tissues have an intrinsic ability to regenerate from a dedicated, tissue-specific stem cell pool. As organisms age, the process of self-regulation or homeostasis begins to slow down with fewer stem cells available for tissue repair. Tissues become more fragile and organs less efficient.

A small-molecule Psora-4 acts as a caloric restriction mimetic to promote longevity in C. elegans.

In populations around the world, the fraction of humans aged 65 and above is increasing at an unprecedented rate. Aging is the main risk factor for the most important degenerative diseases and this demographic shift poses significant social, economic, and medical challenges. Pharmacological interventions directly targeting mechanisms of aging are an emerging strategy to delay or prevent age-dependent diseases.

Inhibition of mTOR decreases insoluble proteins burden by reducing translation in C. elegans.

Aging animals accumulate insoluble proteins as a consequence of a decline of proteostatic maintenance with age. In Caenorhabditis elegans, for instance, levels of detergent-insoluble proteins increase with age. In longer-lived strains of C.

Lifespan and healthspan benefits of exogenous HS in are independent from effects downstream of mutation.

Caloric restriction (CR) is one of the most effective interventions to prolong lifespan and promote health. Recently, it has been suggested that hydrogen sulfide (HS) may play a pivotal role in mediating some of these CR-associated benefits. While toxic at high concentrations, HS at lower concentrations can be biologically advantageous.

WNT Signaling in Disease.

Developmental signaling pathways control a vast array of biological processes during embryogenesis and in adult life. The WNT pathway was discovered simultaneously in cancer and development. Recent advances have expanded the role of WNT to a wide range of pathologies in humans.

Inhibition of amyloid-induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model.

The abnormal accumulation of β-amyloid peptide (Aβ) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of Aβ-mediated neurotoxicity remain elusive, Aβ has been associated with numerous underlying pathologies, including oxidative and nitrosative stress, inflammation, metal ion imbalance, mitochondrial dysfunction, and even tau pathology. Ergothioneine (ET), a naturally occurring thiol/thione-derivative of histidine, has demonstrated antioxidant and neuroprotective properties against various oxidative and neurotoxic stressors.

Measurement of Respiration Rate in Live .

Mitochondrial function and dysfunction are at the core of aging and involved in many age-dependent diseases. Rate of oxygen consumption is a measure of mitochondrial function and energy production rate. The nematode ) offers an opportunity to study "living" mitochondria without the need for mitochondrial extraction, purification and associated artifacts.

Mitochondrial DNA Damage Does Not Determine Lifespan.

The mitochondrial free radical theory of aging (mFRTA) proposes that accumulation of oxidative damage to macromolecules in mitochondria is a causative mechanism for aging. Accumulation of mitochondrial DNA (mtDNA) damage may be of particular interest in this context. While there is evidence for age-dependent accumulation of mtDNA damage, there have been only a limited number of investigations into mtDNA damage as a determinant of longevity.

Lipid profiling of C. elegans strains administered pro-longevity drugs and drug combinations.

We report the effect of four lifespan modifying drugs and of synergistic combinations of these drugs on lipid profile in Caenorhabditis elegans. We employ ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) to compare the abundance of lipid species in treated and control animals. Adult nematodes were treated with rapamycin, rifampicin, psora-4 and allantoin and combinations of these compounds and the resulting change in lipid profiles, specifically in those of triacylglycerol (TAG), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were determined.

Drug Synergy Slows Aging and Improves Healthspan through IGF and SREBP Lipid Signaling.

There is growing interest in pharmacological interventions directly targeting the aging process. Pharmacological interventions against aging should be efficacious when started in adults and, ideally, repurpose existing drugs. We show that dramatic lifespan extension can be achieved by targeting multiple, evolutionarily conserved aging pathways and mechanisms using drug combinations.

Clonal expansion of mitochondrial DNA deletions is a private mechanism of aging in long-lived animals.

Disruption of mitochondrial metabolism and loss of mitochondrial DNA (mtDNA) integrity are widely considered as evolutionarily conserved (public) mechanisms of aging (López-Otín et al., Cell, 153, 2013 and 1194). Human aging is associated with loss in skeletal muscle mass and function (Sarcopenia), contributing significantly to morbidity and mortality.

Identification of a previously undetected metabolic defect in the Complex II Caenorhabditis elegans mev-1 mutant strain using respiratory control analysis.

Hypometabolism may play an important role in the pathogenesis of ageing and ageing-related diseases. The nematode Caenorhabditis elegans offers the opportunity to study "living mitochondria" in a small (~1 mm) animal replete with a highly stereotypical, yet complex, anatomy and physiology. Basal oxygen consumption rate is often employed as a proxy for energy metabolism in this context.

The Role of Mitochondrial Non-Enzymatic Protein Acylation in Ageing.

In recent years, various large-scale proteomic studies have demonstrated that mitochondrial proteins are highly acylated, most commonly by addition of acetyl and succinyl groups. These acyl modifications may be enzyme catalysed but can also be driven non-enzymatically. The latter mechanism is promoted in mitochondria due to the nature of the mitochondrial microenvironment, which is alkaline and contains high concentrations of acyl-CoA species.

Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model.

Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear.

C. elegans miro-1 Mutation Reduces the Amount of Mitochondria and Extends Life Span.

Mitochondria play a critical role in aging, however, the underlying mechanism is not well understood. We found that a mutation disrupting the C. elegans homolog of Miro GTPase (miro-1) extends life span.

Caenorhabditis elegans: What We Can and Cannot Learn from Aging Worms.

Significance: The nematode Caenorhabditis elegans is a widely used model organism for research into aging. However, nematodes diverged from other animals between 600 and 1300 million years ago. Beyond the intuitive impression that some aspects of aging appear to be universal, is there evidence that insights into the aging process of nematodes may be applicable to humans?

Recent Advances: There have been a number of results in nematodes that appear to contradict long-held beliefs about mechanisms and causes of aging.

A continuous-flow C. elegans sorting system with integrated optical fiber detection and laminar flow switching.

We present a high-throughput continuous-flow C. elegans sorting device that works based on integrated optical fiber detection and laminar flow switching. Two types of genetically engineered nematodes are allowed to flow into the device and their genotypes are detected based on their fluorescence, without the need for immobilization, by integrated optical fibers.

The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease.

β-Amyloid (Aβ)-induced toxicity and oxidative stress have been postulated to play critical roles in the pathogenic mechanism of Alzheimer disease (AD). We investigated the in vivo ability of a mitochondria-targeted antioxidant, MitoQ, to protect against Aβ-induced toxicity and oxidative stress in a Caenorhabditis elegans model overexpressing human Aβ. Impairment of electron transport chain (ETC) enzymatic activity and mitochondrial dysfunction are early features of AD.

Effects of lithium on age-related decline in mitochondrial turnover and function in Caenorhabditis elegans.

Aging has been associated with the accumulation of damages in molecules and organelles in cells, particularly mitochondria. The rate of damage accumulation is closely tied to the turnover of the affected cellular components. Perturbing mitochondrial turnover has been shown to significantly affect the rate of deterioration of mitochondrial function with age and to alter lifespan of model organisms.

Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans.

Aims: To investigate the role of endogenous hydrogen sulfide (H2S) in the control of aging and healthspan of Caenorhabditis elegans.

Results: We show that the model organism, C. elegans, synthesizes H2S.

Repression of the mitochondrial peroxiredoxin antioxidant system does not shorten life span but causes reduced fitness in Caenorhabditis elegans.

The mitochondrial free radical theory of aging proposes that aging is a consequence of progressive mitochondrial dysfunction caused by lifelong accumulation of oxidative damage. Aging is therefore expected to accelerate if the rate of this oxidative damage accumulation increases. Studies attempting to test this prediction through modulation of oxidative damage by altering antioxidant defenses have reported conflicting results.

Maximizing signal-to-noise ratio in the random mutation capture assay.

The 'Random Mutation Capture' assay allows for the sensitive quantitation of DNA mutations at extremely low mutation frequencies. This method is based on PCR detection of mutations that render the mutated target sequence resistant to restriction enzyme digestion. The original protocol prescribes an end-point dilution to about 0.

Mitochondrial changes in ageing Caenorhabditis elegans--what do we learn from superoxide dismutase knockouts?

One of the most popular damage accumulation theories of ageing is the mitochondrial free radical theory of ageing (mFRTA). The mFRTA proposes that ageing is due to the accumulation of unrepaired oxidative damage, in particular damage to mitochondrial DNA (mtDNA). Within the mFRTA, the "vicious cycle" theory further proposes that reactive oxygen species (ROS) promote mtDNA mutations, which then lead to a further increase in ROS production.