Longevity Effects Research Articles

The impact of a polyphenol-rich supplement on epigenetic and cellular markers of immune age: a pilot clinical study.

ClinicalTrials.gov, Identifier: NCT05234203.

A mitochondrial unfolded protein response-independent role of DVE-1 in longevity regulation

The special AT-rich sequence-binding (SATB) protein DVE-1 is widely recognized for its pivotal involvement in orchestrating the retrograde mitochondrial unfolded protein response (mitoUPR) in C. elegans. In our study of downstream factors contributing to lifespan extension in sensory ciliary mutants, we find that DVE-1 is crucial for this longevity effect independent of its canonical mitoUPR function. Additionally, DVE-1 also influences lifespan under conditions of dietary restriction and germline loss, again distinct from its role in mitoUPR. Mechanistically, while mitochondrial stress typically prompts nuclear accumulation of DVE-1 to initiate the transcriptional mitoUPR program, these long-lived mutants reduce DVE-1 nuclear accumulation, likely by enhancing its cytosolic translocation. This observation suggests a cytosolic role for DVE-1 in lifespan extension. Overall, our study implies that, in contrast to the more narrowly defined role of the mitoUPR-related transcription factor ATFS-1, DVE-1 may possess broader functions than previously recognized in modulating longevity and defending against stress.

Effect of Himalayan cedar forest longevity on soil properties in the Kumaun Himalaya, Uttarakhand, India

The Himalayan cedar forests in the temperate regions of the Himalaya are crucial for providing ecosystem services such as carbon storage and nutrient maintenance, playing a vital role in combating climate change. This study employs a Dendrochronological approach to examine the impact of Himalayan cedar forest stands on soil properties across five distinct sites in the Kumaun Himalaya. Soil samples were collected from a depth of 0–15 cm and analyzed for total nitrogen (TN), total phosphorus (TP), soil organic carbon (SOC), pH, and C:N ratios. Tree-ring samples were also collected taken from the same sites. Our analysis revealed a positive correlation between tree age and SOC content. Notably, the oldest forests at Jageshwar Dham (480 years) and Hatkalika (413 years) exhibited the highest levels of SOC, TP, and TN, while the youngest forests at Naudunga (135 years) and Patal Bhuwaneshwar (134 years) showed the lowest values. Significant differences in all soil parameters were confirmed through a Tukey post hoc test. Additionally, the relationship between climate and tree growth was analyzed using tree-ring chronologies and meteorological records, indicating that cool and moist spring conditions (February-May) enhance tree growth by increasing soil microbial activity. Our findings emphasize that conserving older natural forests, particularly mature Himalayan cedar forests, is crucial for maintaining soil characteristics, including carbon storage and nutrient levels, to support sustainable soil health and climate change mitigation.

Isolating the Direct Effects of Growth Hormone on Lifespan and Metabolism.

Prior studies show that disrupting somatotropic axis components extends laboratory mouse lifespan, but confounding effects of additional genes and hormones obscure the specific impact of growth hormone (GH) on longevity. We address this issue by using mice with a specific knockout of the GH gene, revealing that disrupting GH alone substantially increases lifespan. The longevity effects are accompanied by altered metabolic fuel utilization, directly linking GH action to aging mechanisms.

Effects of cow feed efficiency, longevity, heterosis, and lifetime productivity on profitability of heifer selection and cow-calf operations

This study investigated factors influencing heifer replacement and cow-calf profitability using 361 cows (born 2011-2018) at the Lacombe Research and Development Centre, Alberta, Canada. Profitability was measured by marginal returns (MR) incorporating feed costs, heifer opportunity cost, calf and cull revenues, and a premium for cows retained in the herd. The study evaluated the linear effects of lifetime productivity, feed efficiency (residual feed intake adjusted for off-test backfat thickness; RFIfat), and genomic retained heterozygosity, an indicator of heterosis, on MR, feed costs, total costs, and net revenue (NR). Lifetime productivity, defined by the cumulative weight of calves weaned, was positively associated with MR and NR (P < 0.01). RFIfat influenced total cost, MR, and NR (P < 0.05), with MR improved by $168.50 cow-1 yr-1 for each unit decrease in RFIfat, although regression and group mean comparisons were not fully consistent. Genomic retained heterozygosity positively impacted MR and NR, with a 10% increase enhanced MR and NR by $21.80 and $20.50 cow-1 yr-1, respectively. Cow breed type did not affect longevity, MR, or NR. In conclusion, RFIfat and genomic diversity were important factors to consider in heifer replacement decisions when lifetime DMI was estimated as described in the present study.

Evidence to support cultivated fruiting body of Ophiocordyceps sinensis (Ascomycota)'s role in relaxing airway smooth muscle

Ethnopharmacological relevanceOphiocordyceps sinensis (O. sinensis) is a genus of Ascomycete fungus that is endemic to the alpine meadows of the Tibetan Plateau and adjoining Himalayas. It has been used traditionally as a tonic to improve respiratory health in ancient China as well as to promote vitality and longevity. Bioactive components found in O. sinensis such as adenosine, cordycepin, 3-deoxyadenosine, L-arginine and polysaccharides have gained increasing interest in recent years due to their antioxidative and other properties, which include anti-asthmatic, antiviral, immunomodulation and improvement of general health. Aim of the studyThis study's primary aim was to investigate the effect of a cultivated fruiting body of O. sinensis strain (OCS02®) on airways patency and the secondary focus was to investigate its effect on the lifespan of Caenorhabditis elegans. Materials and methodsA cultivated strain, OCS02®, was employed and the metabolic profile of its cold-water extract (CWE) was analysed through liquid chromatography-mass spectrometry (LC-MS). Organ bath approach was used to investigate the pharmacological properties of OCS02® CWE when applied on airway tissues obtained from adult male Sprague-Dawley rats. The airway relaxation mechanisms of OCS02® CWE were explored using pharmacological tools, where the key regulators in airway relaxation and constriction were investigated. For the longevity study, age-synchronised, pos-1 RNAi-treated wild-type type Caenorhabditis elegans at the L4 stage were utilised for a lifespan assay. ResultsVarious glycopeptides and amino acids, particularly a high concentration of L-arginine, were identified from the LC-MS analysis. In airway tissues, OCS02® CWE induced a significantly greater concentration-dependent relaxation when compared to salbutamol. The relaxation response was significantly attenuated in the presence of NG-Nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) and several K+ channel blockers. The longevity effect induced by OCS02® CWE (5 mg/mL and above) was observed in C. elegans by at least 17%. ConclusionsThese findings suggest that the airway relaxation mechanisms of OCS02® CWE involved cGMP-dependent and cGMP-independent nitric oxide signalling pathways. This study provides evidence that the cultivated strain of OCS02® exhibits airway relaxation effects which supports the traditional use of its wild O. sinensis in strengthening respiratory health.

Unraveling anti-aging mystery of green tea in C. elegans: Chemical truth and multiple mechanisms

Tea drinking impacts aging and aging-related diseases. However, knowledge of anti-aging molecules other than the major catechins in complex tea extracts remains limited. Here we used Caenorhabditis elegans to analyze the longevity effects of tea extracts and constituents comprehensively. We found that the hot water extract of green tea prolonged lifespan and heathspan. Further, the MeOH fraction prolonged lifespan significantly longer than other fractions. Correlation analysis between mass spectroscopic data and anti-aging activity suggests that ester-type catechins (ETCs) are the major anti-aging components, including 4 common ETCs, 6 phenylpropanoid-substituted ester-type catechins (PSECs), 5 cinnamoylated catechins (CCs), 7 ester-type flavoalkaloids (ETFs), and 4 cinnamoylated flavoalkaloids (CFs). CFs (200 μM) are the strongest anti-aging ETCs (with the longest 73% lifespan extension). Green tea hot water extracts and ETCs improved healthspan by enhancing stress resistance and reducing ROS accumulation. The mechanistic study suggests that they work by multiple pathways. Moreover, ETCs modulated gut microbial homeostasis, increased the content of short-chain fatty acids, and reduced fat content. Altogether, our study provides new evidence for the anti-aging benefits of green tea and insights into a deep understanding of the chemical truth and multi-target mechanism.

Identification and time evolution of thionyl chloride (SOCl2) radiolysis products

Abstract Innovative solutions are needed to reduce the amount of high-level waste generated by used nuclear fuel recycling strategies to support the widespread adoption of sustainable nuclear fission energy technologies. To this end, a new sulfur chloride-based process has been developed to recycle zirconium alloy-based materials, which make up a significant fraction of high-level radioactive waste. To support the continued development of this process, we present new data on the potential reaction pathways over time of the products arising from the gamma and electron beam radiolysis of neat thionyl chloride (SOCl2). Interrogation of the gamma irradiated liquid by Raman spectroscopy provided more conclusive identification of the SOCl2 degradation products, specifically sulfur dichloride (SCl2), molecular chlorine (Cl2), sulfur dioxide (SO2), and sulfuryl chloride (SO2Cl2). In comparison, the high dose rate (∼107 Gy s−1) electron beam irradiations formed significantly more degradation products. For both cobalt-60 gamma and electron beam irradiations, the observed degradation products were found to evolve as a function of time post-irradiation via the same reaction pathways, with indication of a solvent regeneration mechanism. These findings are fortuitous for process development, as such a mechanism would be beneficial for process longevity and cost effectiveness.

Longevity studies for the CMS Drift Tubes towards HL-LHC

The High Luminosity LHC (HL-LHC) program will pose a great challenge for the CMS Muon System. Existing subdetectors, which consist of Drift Tubes (DT), Resistive Plate Chambers (RPC) and Cathode Strip Chambers (CSC), will have to operate at 5 times larger instantaneous luminosity than the designed for, and, consequently, will have to sustain about 10 times the original LHC integrated luminosity. Longevity of DT system will be crucial to ensure a good performance in the CMS barrel region. Assessing DT performance is part of the upgrade program. In this talk will be reported the outcome of the accelerated irradiation studies, carried on at the CERN Gamma Irradiation Facility (GIF++) and recently concluded. These studies allowed to estimate performance of DT up to 3 times HL-LHC, and to plan a strategy to keep the longevity effects under control.

Molecular Mechanisms of Genotype-Dependent Lifespan Variation Mediated by Caloric Restriction: Insight from Wild Yeast Isolates.

Caloric restriction (CR) is known to extend lifespan across different species and holds great promise for preventing human age-onset pathologies. However, two major challenges exist. First, despite extensive research, the mechanisms of lifespan extension in response to CR remain elusive. Second, genetic differences causing variations in response to CR and genetic factors contributing to variability of CR response on lifespan are largely unknown. Here, we took advantage of natural genetic variation across 46 diploid wild yeast isolates of Saccharomyces species and the lifespan variation under CR conditions to uncover the molecular factors associated with CR response types. We identified genes and metabolic pathways differentially regulated in CR-responsive versus non-responsive strains. Our analysis revealed that altered mitochondrial function and activation of GCN4-mediated environmental stress response are inevitably linked to lifespan variation in response to CR and a unique mitochondrial metabolite might be utilized as a predictive marker for CR response rate. In sum, our data suggests that the effects of CR on longevity may not be universal, even among the closely related species or strains of a single species. Since mitochondrial-mediated signaling pathways are evolutionarily conserved, the dissection of related genetic pathways will be relevant to understanding the mechanism by which CR elicits its longevity effect.

Effect of Longevity on Economic Growth, Accounting for Variability in Demographic Transition: Evidence for Pakistan using ARDL Bounds Testing Approach

Rising longevity due to access to better health services affects the growth and composition of the population differently than birth rates. In addition, empirical evidence of the effects of rising longevity on standards of living is ambiguous. From the perspective of developing nations, it is important to understand how rising longevity affects national prosperity, as this allows governments to develop programs for increasing investment in the health sector. This study explicitly tested varying intertemporal impacts of rising longevity on the GDP per capita of Pakistan between 1967 and 2020. An Autoregressive Distributed Lag (ARDL) bounds testing approach to cointegration was used to estimate and compare short-run and long-run estimates of longevity. The results indicated that a 1% increase in longevity increased the growth rate of GDP per capita in Pakistan by 0.64% in the long-run. In addition, a 1% increase in life expectancy at birth above 62 years increased economic growth by an additional 0.009%. In general, the estimated effect of increased longevity varied by stages of demographic transition in Pakistan.

Lactobacillus paracasei subsp. paracasei 2004 improves health and lifespan in Caenorhabditis elegans

Recent research has highlighted the importance of the gut microbiome in regulating aging, and probiotics are interventions that can promote gut health. In this study, we surveyed several novel lactic acid bacteria to examine their beneficial effect on organismal health and lifespan in C. elegans. We found that animals fed some lactic acid bacteria, including L. acidophilus 1244 and L. paracasei subsp. paracasei 2004, grew healthy. Supplementation with the lactic acid bacterial strains L. acidophilus 1244 or L. paracasei subsp. paracasei 2004 significantly improved health, including food consumption, motility, and resistance to oxidative stressor, hydrogen peroxide. Our RNA-seq analysis showed that supplementation with L. paracasei subsp. paracasei 2004 significantly increased the expression of daf-16, a C. elegans FoxO homolog, as well as genes related to the stress response. Furthermore, daf-16 deletion inhibited the longevity effect of L. paracasei subsp. paracasei 2004 supplementation. Our results suggest that L. paracasei subsp. paracasei 2004 improves health and lifespan in a DAF-16-dependent manner.

Effects of Endogenous Longevity on Transitional Dynamics of Intergenerational Mobility

ABSTRACT This paper explains the mechanism that causes the two motions of intergenerational mobility, monotonic motion and cyclical motion. Increasing longevity encourages incentives for education investment while decreasing transfers, which is the funding source for education. If longevity increases slowly, mobility increases monotonically. However, if longevity increases rapidly with economic development, mobility is cyclical owing to a largely decreasing transfer. This result is consistent with the empirical evidence in the literature on intergenerational mobility. In fact, China, where longevity increased rapidly, experienced a cyclical motion of mobility, whereas Norway, where longevity increased slowly, has experienced a monotonic motion of mobility.

Metformin normalizes mitochondrial function to delay astrocyte senescence in a mouse model of Parkinson’s disease through Mfn2-cGAS signaling

BackgroundSenescent astrocytes play crucial roles in age-associated neurodegenerative diseases, including Parkinson’s disease (PD). Metformin, a drug widely used for treating diabetes, exerts longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined.MethodsLong culture-induced replicative senescence model and 1-methyl-4-phenylpyridinium/α-synuclein aggregate-induced premature senescence model, and a mouse model of PD were used to investigate the effect of metformin on astrocyte senescence in vivo and in vitro. Immunofluorescence staining and flow cytometric analyses were performed to evaluate the mitochondrial function. We stereotactically injected AAV carrying GFAP-promoter-cGAS-shRNA to mouse substantia nigra pars compacta regions to specifically reduce astrocytic cGAS expression to clarify the potential molecular mechanism by which metformin inhibited the astrocyte senescence in PD.ResultsWe showed that metformin inhibited the astrocyte senescence in vitro and in PD mice. Mechanistically, metformin normalized mitochondrial function to reduce mitochondrial DNA release through mitofusin 2 (Mfn2), leading to inactivation of cGAS-STING, which delayed astrocyte senescence and prevented neurodegeneration. Mfn2 overexpression in astrocytes reversed the inhibitory role of metformin in cGAS-STING activation and astrocyte senescence. More importantly, metformin ameliorated dopamine neuron injury and behavioral deficits in mice by reducing the accumulation of senescent astrocytes via inhibition of astrocytic cGAS activation. Deletion of astrocytic cGAS abolished the suppressive effects of metformin on astrocyte senescence and neurodegeneration.ConclusionsThis work reveals that metformin delays astrocyte senescence via inhibiting astrocytic Mfn2-cGAS activation and suggest that metformin is a promising therapeutic agent for age-associated neurodegenerative diseases.

Reactive Oxygen Species Scavenging Injectable Hydrogel Potentiates the Therapeutic Potential of Mesenchymal Stem Cells in Skin Flap Regeneration.

Cell-based therapies offer tremendous potential for skin flap regeneration. However, the hostile microenvironment of the injured tissue adversely affects the longevity and paracrine effects of the implanted cells, severely reducing their therapeutic effectiveness. Here, an injectable hydrogel (nGk) with reactive oxygen species (ROS) scavenging capability, which can amplify the cell viability and functions of encapsulated mesenchymal stem cells (MSCs), is employed to promote skin flap repair. nGk is formulated by dispersing manganese dioxide nanoparticles (MnO2 NPs) in a gelatin/κ-carrageenan hydrogel, which exhibits satisfactory injectable properties and undergoes a sol-gel phase transition at around 40 °C, leading to the formation of a solid gel at physiological temperature. MnO2 NPs enhance the mechanical properties of the hydrogel and give it the ability to scavenge ROS, thus providing a cell-protective system for MSCs. Cell culture studies show that nGk can mitigate the oxidative stress, improve cell viability, and boost stem cell paracrine function to promote angiogenesis. Furthermore, MSC-loaded nGk (nGk@MSCs) can improve the survival of skin flaps by promoting angiogenesis, reducing inflammatory reactions, and attenuating necrosis, providing an effective approach for tissue regeneration. Collectively, injectable nGk has substantial potential to enhance the therapeutic benefits of MSCs, making it a valuable delivery system for cell-based therapies.

Empirical study about the effect of parental and child longevity on child education under COVID-19

Empirical study about the effect of parental and child longevity on child education under COVID-19

Ergothioneine promotes longevity and healthy aging in male mice

Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age. This was compatible with dramatical suppression by ERGO of the age-related increments in plasma biomarkers (BMs) such as the chemokine ligand 9, creatinine, symmetric dimethylarginine, urea, asymmetric dimethylarginine, quinolinic acid, and kynurenine. The oral intake of ERGO also rescued age-related impairments in learning and memory ability, which might be associated with suppression of the age-related decline in hippocampal neurogenesis and TDP43 protein aggregation and promotion of microglial shift to the M2 phenotype by ERGO ingestion. Ingestion of ERGO may promote longevity and healthy aging in male mice, possibly through multiple biological mechanisms.

Sesamolin has the ability to induce longevity effects on the Caenorhabditis elegans, and the mechanism depends on the SIR-2.1 and AAK-2 proteins

Sesamolin, one of the prominent lignans in sesame seeds, offers diverse physiological benefits. However, the longevity effects and mechanisms of sesamolin remain unclear. We hypothesized that sesamolin can exert the longevity effects in the Caenorhabditis (C.) elegans when prepared with the γ-cyclodextrin to form an inclusion complex (named γCD-SM). In this study, the γCD-SM was prepared, and the lifespan assays, health indexes, and loss-of-function assays in the C. elegans or mutants were conducted. The results demonstrated that the γCD-SM significantly extended the C. elegans’ lifespan and improved the health indexes, such as the pharyngeal pumping and body bends. The longevity effects of the γCD-SM were found to depend on the signaling of the SIR-2.1 and AAK-2. In conclusion, the γ-CD inclusion is a crucial step for assessing the sesamolin's longevity effects in the C. elegans. This study confirms that sesamolin exhibits the longevity effects, and its mechanism relies on the signaling of the SIR-2.1 and the AAK-2 proteins, suggesting its potential as a health-promoting ingredient.

Longevity and anti-aging effects of curcumin supplementation.

Aging is a gradual and irreversible process that is accompanied by an overall decline in cellular function and a significant increase in the risk of age-associated disorders. Generally, delaying aging is a more effective method than treating diseases associated with aging. Currently, researchers are focused on natural compounds and their therapeutic and health benefits. Curcumin is the main active substance that is present in turmeric, a spice that is made up of the roots and rhizomes of the Curcuma longa plant. Curcumin demonstrated a positive impact on slowing down the aging process by postponing age-related changes. This compound may have anti-aging properties by changing levels of proteins involved in the aging process, such as sirtuins and AMPK, and inhibiting pro-aging proteins, such as NF-κB and mTOR. In clinical research, this herbal compound has been extensively examined in terms of safety, efficacy, and pharmacokinetics. There are numerous effects of curcumin on mechanisms related to aging and human diseases, so we discuss many of them in detail in this review.

Impact of a glyphosate-based herbicide on the longevity, fertility, and transgenerational effects on Chrysopa pallens (Rambur) (Neuroptera: Chrysopidae).

Glyphosate-based herbicides (GBHs) are common herbicide formulations used in the field and are increasingly used worldwide with the widespread cultivation of herbicide-tolerant genetically modified crops. As a result, the risk of arthropod exposure to GBH is increasing rapidly. Chrysopa pallens (Rambur) (Neuroptera: Chrysopidae) is a common predatory natural enemy in agroecosystems, which is exposed to GBH (Roundup®) while preying on pests. To identify and characterize the potential effects of GBH on C. pallens, the life tables of C. pallens larvae and adults fed with GBH were constructed. Moreover, the effects of GBH treatment on the expression of genes involved in insulin signalling in adults were analyzed using qRT-PCR. The results showed that GBH treatment altered the pupal period and preadult stage of C. pallens larvae. However, it did no effect on longevity, fecundity, and population parameters and two insulin receptor genes (InR1, InR2), a serine/threonine kinase (Akt), an extracellular-signal-regulated kinase (erk), and vitellogenin (Vg1) expression of C. pallens. Adults feeding on GBH significantly altered development, longevity, and differences in the mean generation time of the F0 generation. However, GBH feeding only minimally influenced the growth and population parameters of the F1 generation. In addition, InR1, InR2, erk, and Vg1 expression in the F0 generation were downregulated on the fifth day of feeding on GBH. Furthermore, the expression levels of InR1, InR2, Akt, erk, and Vg1 in C. pallens decreased with the increase of GBH concentration, although the expression levels returned to control levels on the tenth day. Overall, the consumption of the GBH by larvae and adults of C. pallens had minimal effect on the growth and population parameters of C. pallens. The findings of this study can provide a reference for elucidating the environmental risks of GBH, guiding the optimal use of glyphosate in agricultural practices in the future.