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1.
J Ethnopharmacol ; 336: 118727, 2025 Jan 10.
Article in English | MEDLINE | ID: mdl-39182700

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiocordyceps 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 STUDY: This 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 METHODS: A 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. RESULTS: Various 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%. CONCLUSIONS: These 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.


Subject(s)
Fruiting Bodies, Fungal , Muscle, Smooth , Rats, Sprague-Dawley , Animals , Male , Fruiting Bodies, Fungal/chemistry , Muscle, Smooth/drug effects , Muscle Relaxation/drug effects , Rats , Trachea/drug effects , Trachea/metabolism , Longevity/drug effects , Hypocreales
2.
Biomolecules ; 14(9)2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39334855

ABSTRACT

The relationship of Amyotrophic Lateral Sclerosis, Parkinson's disease, and other age-related neurodegenerative diseases with mitochondrial dysfunction has led to our study of the mitochondrial fission gene Drp1 in Drosophila melanogaster and aspects of aging. Previously, the Drp1 protein has been demonstrated to interact with the Drosophila Bcl-2 mitochondrial proteins, and Drp1 mutations can lead to mitochondrial dysfunction and neuronal loss. In this study, the Dopa decarboxylase-Gal4 (Ddc-Gal4) transgene was exploited to direct the expression of Drp1 and Drp1-RNAi transgenes in select neurons. Here, the knockdown of Drp1 seems to compromise locomotor function throughout life but does not alter longevity. The co-expression of Buffy suppresses the poor climbing induced by the knockdown of the Drp1 function. The consequences of Drp1 overexpression, which specifically reduced median lifespan and diminished climbing abilities over time, can be suppressed through the directed co-overexpression of pro-survival Bcl-2 gene Buffy or by the co-knockdown of the pro-cell death Bcl-2 homologue Debcl. Alteration of the expression of Drp1 acts to phenocopy neurodegenerative disease phenotypes in Drosophila, while overexpression of Buffy can counteract or rescue these phenotypes to improve overall health. The diminished healthy aging due to either the overexpression of Drp1 or the RNA interference of Drp1 has produced novel Drosophila models for investigating mechanisms underlying neurodegenerative disease.


Subject(s)
Aging , Drosophila Proteins , Drosophila melanogaster , Phenotype , Animals , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Aging/genetics , Aging/metabolism , Longevity/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Dynamins/genetics , Dynamins/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Cytoskeletal Proteins , GTP-Binding Proteins
3.
Aging (Albany NY) ; 16(17): 12168-12190, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39264584

ABSTRACT

Current rejuvenation strategies, which range from calorie restriction to in vivo partial reprogramming, only improve a few specific cellular processes. In addition, the molecular mechanisms underlying these approaches are largely unknown, which hinders the design of more holistic cellular rejuvenation strategies. To address this issue, we developed SINGULAR (Single-cell RNA-seq Investigation of Rejuvenation Agents and Longevity), a cell rejuvenation atlas that provides a unified system biology analysis of diverse rejuvenation strategies across multiple organs at single-cell resolution. In particular, we leverage network biology approaches to characterize and compare the effects of each strategy at the level of intracellular signaling, cell-cell communication, and transcriptional regulation. As a result, we identified master regulators orchestrating the rejuvenation response and propose that targeting a combination of them leads to a more holistic improvement of age-dysregulated cellular processes. Thus, the interactive database accompanying SINGULAR is expected to facilitate the future design of synthetic rejuvenation interventions.


Subject(s)
Rejuvenation , Rejuvenation/physiology , Animals , Humans , Gene Regulatory Networks , Single-Cell Analysis , Systems Biology , Gene Expression Regulation , Signal Transduction , Longevity/genetics , Longevity/physiology , Cell Communication
4.
Aging (Albany NY) ; 16(17): 12108-12122, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39264580

ABSTRACT

Understanding the relationship between activity over the entire lifespan and longevity is an important facet of aging research. We present a comprehensive framework for the statistical analysis of longitudinal activity and behavioral monitoring and their relationship with age-at-death at the individual level, highlighting the importance of advanced methodological approaches in aging research. The focus is on animal models, where continuous monitoring activity in terms of movement, reproduction and behaviors over the entire lifespan is feasible at the individual level. We specifically demonstrate the methodology with data on activity monitoring for Mediterranean fruit flies. Advanced statistical methodologies to explore the interface between activity and age-at-death include functional principal component analysis, concurrent regression, Fréchet regression and point processes. While the focus of this perspective is on relating age-at-death with data on movement, reproduction, behavior and nutrition of Mediterranean fruit flies, the methodology equally pertains to data from other species, including human data.


Subject(s)
Longevity , Animals , Longevity/physiology , Humans , Aging/physiology , Behavior, Animal/physiology , Ceratitis capitata/physiology , Longitudinal Studies , Reproduction/physiology
5.
Exp Gerontol ; 196: 112586, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39303817

ABSTRACT

The Growth Hormone Receptor (GHR) gene encodes a protein that is essential for mediating the biological effects of growth hormone (GH). A series of molecular events are set off when GH binds to its receptor, resulting in a variety of physiological reactions linked to development, growth, and metabolism. Recently a particular genetic variation, within the GHR gene that is labeled as the "d3GHR," which lacks exon 3 was associated with longevity. This specific deletion isoform was connected to changes in the structure of the GHR protein, which may have an impact on the GHR's function. To test in vitro the advantage of the d3 carrier that may link to longevity, we employed the CRISPR/Cas9 technique to produce two isoforms: the homozygotes isoform (d3/d3) and the heterozygotes isoform (d3/fl) using HEK293 cell line. The CRISPR editing effectiveness was >85 %, indicating that we had successfully built the Cas9-gRNA complex that is appropriate for the GHR gene. The viability of the resulted isoform cells was examined under three environmental stressors that mimic some aging processes. In addition, we examined the GHR signaling pathway by selecting potential downstream genes in the GHR signaling cascade. The results show that heterozygotes cells demonstrated higher survival rates under UV radiation compared with the WT cells (87 % compared with 67 % for the WT cells when exposed to 2 min of UV radiation), and in fasting conditions, the d3GHR cells showed a 15 % greater viability than the WT cells. Moreover, the baseline expression levels (without intervention) of the IGF1 and JAK/STAT genes signaling pathways significantly declined in the homozygotes cells compared with the WT (p < 0.05). This noteworthy finding might offer a practical approach to test illness prevention and give the scientific community critical new insights on mechanism associated with lifespan.


Subject(s)
CRISPR-Cas Systems , Longevity , Protein Isoforms , Receptors, Somatotropin , Humans , Longevity/genetics , HEK293 Cells , Receptors, Somatotropin/genetics , Receptors, Somatotropin/metabolism , Protein Isoforms/genetics , Signal Transduction , Gene Knockout Techniques , Cell Survival , Stress, Physiological , Gene Editing/methods
6.
Int J Mol Sci ; 25(18)2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39337674

ABSTRACT

Salvia leucantha is a perennial herb of the genus Salvia in the family Labiatae, which has a wide range of biological activities, mainly including inhibition of acetylcholinesterase, antibacterial, and anti-inflammatory activity. To explore the protective effects and mechanism of action of S. leucantha on Alzheimer's disease (AD), the anti-AD activity of SLE (extracts of S. leucantha) was determined by using a transgenic Caenorhabditis elegans (C. elegans) model (CL4176). Analyses included paralysis assay, phenotypic experiments, transcriptome sequencing, RNA interference (RNAi), heat shock assays, and gas chromatography-mass spectrometry (GC-MS). SLPE (S. leucantha petroleum ether extract) could significantly delay CL4176 paralysis and extend the longevity of C. elegans N2 without harmful effects. A total of 927 genes were significantly changed by SLPE treatment in C. elegans, mainly involving longevity regulatory pathways-nematodes, drug metabolism-cytochrome P450, and glutathione metabolic pathways. RNAi showed that SLPE exerted its anti-AD activity through up-regulation of the gene gst-5; the most abundant compound in SLPE analyzed by GC-MS was 2,4-Di-tert-butylphenol (2,4-DTBP), and the compound delayed nematode paralysis. The present study suggests that active components in S. leucantha may serve as new-type anti-AD candidates and provide some insights into their biological functions.


Subject(s)
Alzheimer Disease , Caenorhabditis elegans Proteins , Caenorhabditis elegans , Disease Models, Animal , Plant Extracts , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/drug therapy , Up-Regulation/drug effects , Salvia/chemistry , Longevity/genetics , Longevity/drug effects , Animals, Genetically Modified , RNA Interference , Glutathione Transferase/genetics , Glutathione Transferase/metabolism
7.
Nutrients ; 16(18)2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39339711

ABSTRACT

Women typically outlive men, yet they often experience greater frailty and a higher incidence of chronic diseases as they age. By exploring the biological foundations of aging, with a particular focus on telomere dynamics, this manuscript aims to describe how dietary and lifestyle choices can significantly influence the aging process. The review comprehensively examines current research, underscoring the power of nutrition to counteract age-related changes, support healthy aging, and maintain vitality and beauty in women. The exploration of telomeres-the protective caps at the ends of chromosomes-reveals how they serve as markers of cellular aging and are potential targets for interventions aimed at enhancing women's longevity and quality of life. This study also emphasizes the importance of sex-specific approaches and precision medicine in understanding the unique health challenges women face as they age. By proposing targeted strategies, the review seeks to address these challenges, offering insights into preventive measures that can foster resilience, promote well-being, and extend healthy life expectancy in women. Ultimately, this work provides a sophisticated understanding of the aging process in women, highlighting the pivotal role of tailored interventions in preserving both health and beauty.


Subject(s)
Aging , Beauty , Nutritional Status , Telomere , Humans , Female , Aging/physiology , Women's Health , Quality of Life , Longevity , Healthy Aging , Life Style , Diet
8.
Nutrients ; 16(18)2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39339719

ABSTRACT

BACKGROUND: Fasting potentially alters the aging process induced by obesity by regulating telomere integrity, which is related to longevity genes. However, the impact of periodic fasting (PF) on the expression of longevity genes, particularly Forkhead Box O Transcription Factors (FOXO3a) and the Human Telomerase Reverse Transcriptase (hTERT), is not fully understood. This study aimed to analyze the effects of PF, specifically on FOXO3a, hTERT expression, and other associated factors. METHODS: A quasi-experimental 10-day study was conducted in Surabaya, East Java, Indonesia. This study consisted of an intervention group (PFG), which carried out PF for ten days using a daily 12 h time-restricted eating protocol, and a control group (CG), which had daily meals as usual. FOXO3a and hTERT expression were analyzed by quantitative real-time qPCR. A paired t-test/Wilcoxon test, independent t-test/Mann-Whitney U-test, and Spearman's correlation test were used for statistical analysis. RESULT: Thirty-six young men participated in this study. During the post-test period, FOXO3a expression in the PFG increased 28.56 (±114.05) times compared to the pre-test, but the difference was not significant. hTERT expression was significantly higher in both the CG and PFG. The hTERT expression in the PFG was 10.26 (±8.46) times higher than in the CG, which was only 4.73 (±4.81) times higher. There was also a positive relationship between FOXO and hTERT in the CG. CONCLUSIONS: PF significantly increased hTERT expression in the PFG; however, no significant increase was found in FOXO3a expression. PF regimens using the 12 h time-restricted eating approach may become a potential strategy for preventing obesity-induced premature aging by regulating longevity gene expression.


Subject(s)
Fasting , Forkhead Box Protein O3 , Longevity , Obesity , Overweight , Telomerase , Humans , Male , Forkhead Box Protein O3/genetics , Forkhead Box Protein O3/metabolism , Longevity/genetics , Obesity/genetics , Telomerase/genetics , Telomerase/metabolism , Overweight/genetics , Adult , Young Adult , Indonesia , Gene Expression Regulation
9.
Food Funct ; 15(19): 9849-9862, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39240213

ABSTRACT

Soy isoflavones from soy sauce residues have important biological activities. However, the anti-aging and reproduction-promoting effects of glycitein are still rarely reported. Here, we systematically evaluated and explored the anti-aging and reproduction-promoting effects of glycitein in Caenorhabditis elegans (C. elegans). Firstly, we analyzed the effects of glycitein on the lifespan under normal and heat stress, reproduction, locomotion, and reactive oxygen species (ROS) levels of C. elegans. The results showed that 100 µmol L-1 glycitein increased the anti-stress ability of nematodes and activated the antioxidant defense system. Secondly, transcriptomic and proteomic technologies were further used to explore in-depth the anti-aging and reproduction-promoting mechanisms of glycitein in C. elegans. The results showed that both differentially expressed proteins (DEPs) including PDE-2 and MSRA-1 and differentially expressed genes (DEGs) including skpo-2 and cytochrome P450 (cyp-35A3, cyp-35A5, cyp-35C1, cyp-35D1) were associated with the extension of the lifespan and the exertion of antioxidant capacity. VIT-1, plx-2, and Y73F8A.35 were related to promoting reproduction. ASP-1, DNJ-10, and abu-1 were related to the anti-stress ability of glycitein. Pathway analysis revealed that the longevity regulation pathway and FOXO signaling pathway were regulated by the changes in genes and proteins to improve the lifespan of the nematode. Moreover, hydrogenase regulation, longevity regulation, and lipid metabolism were regulated by the changes in genes and proteins to promote the reproduction of nematodes. This study not only demonstrates a viable strategy for utilizing soy sauce residues, but also provides a theoretical foundation and developmental insights for the future application of glycitein.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Isoflavones , Proteomics , Reproduction , Transcriptome , Animals , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Caenorhabditis elegans/genetics , Reproduction/drug effects , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Isoflavones/pharmacology , Transcriptome/drug effects , Longevity/drug effects , Aging/drug effects , Antioxidants/pharmacology , Reactive Oxygen Species/metabolism
10.
Nat Commun ; 15(1): 8378, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39333094

ABSTRACT

Inbreeding depression has been documented in various fitness traits in a wide range of species and taxa, however, the mutational basis is not yet well understood. We investigate how putatively deleterious variation influences fitness and is shaped by individual ancestry by re-sequencing complete genomes of 37 individuals in a natural arctic fox (Vulpes lagopus) population subjected to both inbreeding depression and genetic rescue. We find that individuals with high proportion of homozygous loss of function genotypes (LoFs), which are predicted to exert a strong effect on fitness, generally have lower lifetime reproductive success and live shorter lives compared with individuals with lower proportion of LoFs. We also find that juvenile survival is negatively associated with the proportion of homozygous missense genotypes and positively associated with genome wide heterozygosity. Our results demonstrate that homozygosity of strongly and moderately deleterious mutations can be an important cause of trait specific inbreeding depression in wild populations, and mark an important step towards making more informed decisions using applied conservation genetics.


Subject(s)
Endangered Species , Foxes , Inbreeding Depression , Longevity , Reproduction , Animals , Longevity/genetics , Reproduction/genetics , Inbreeding Depression/genetics , Foxes/genetics , Male , Female , Homozygote , Mutation , Genetic Fitness , Genotype , Inbreeding , Loss of Function Mutation , Heterozygote , Genetics, Population , Genome/genetics
11.
Sci Rep ; 14(1): 20727, 2024 09 05.
Article in English | MEDLINE | ID: mdl-39237643

ABSTRACT

Given the growing interest in manipulating microbiota to enhance the fitness of mass-reared insects for biological control, this study investigated the impact of an artificial diet on the microbiota composition and performance of Orius strigicollis. We compared the microbiota of O. strigicollis fed on an artificial diet and moth eggs via culturing and 16S rRNA gene amplicon sequencing. Subsequently, we assessed life history traits and immune gene expression of O. strigicollis fed on the artificial diet supplemented with Pantoea dispersa OS1. Results showed that microbial diversity remained largely unaffected by the artificial diet, with similar microbiota compositions in both diet groups. OS1, a minor member of the microbiota but significantly enriched in bugs fed on the artificial diet, improved nymphal survival rates and shifted adult longevity-reproduction life history in females. Additionally, OS1 supplementation elevated the transcription of antimicrobial peptide diptericin. According to population parameters, the group receiving OS1 only during the nymphal stage showed higher population growth potential compared to the group supplemented across all life stages. These findings reveal the resilience of O. strigicollis microbiota under distinct dietary conditions and highlight the potential of using natural symbionts and specific supplementation regimes to improve Orius rearing for future biocontrol programs.


Subject(s)
Microbiota , Animals , Female , Heteroptera/microbiology , Diet , Dietary Supplements , RNA, Ribosomal, 16S/genetics , Pantoea/physiology , Pantoea/genetics , Nymph/microbiology , Nymph/growth & development , Moths/microbiology , Moths/growth & development , Male , Animal Feed , Longevity
12.
Food Res Int ; 194: 114885, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39232523

ABSTRACT

The Chinese bayberry pomace wine (CPW) was prepared with the assisted fermentation of lactic acid bacteria and acetic acid bacteria, and its antioxidant effect on Drosophila melanogaster was researched. After mixed fermentation, CPW had a better color, which means there was more retention of anthocyanins, and the functional activity of anthocyanins could enhance the antioxidant capacity of flies. We found that the lifespan of flies exposed to CPW was prolonged, and the reproductive capacity of these flies was decreased. The food intake of flies was also influenced by CPW with gender differences. Furthermore, CPW alleviated the excessive proliferation of the intestinal precursor cells of H2O2-induced flies and activated the transcription level of antibacterial peptide genes. CPW had a protective effect on H2O2-induced acute injury flies, with an increased survival rate, enhanced SOD and CAT activities, and decreased malondialdehyde (MDA) content in flies. The expression of oxidative stress-related genes including CuZn-SOD, Mn-SOD, and CAT was also significantly upregulated by CPW, but the downregulation effect of CPW on age-related gene expression such as methuselah (MTH), the target of rapamycin (TOR) and ribosomaiprotein S6 kinase (S6K) was sex-specific. These results suggested that CPW played an important role in anti-oxidative stress injury, which was beneficial to promoting the reuse of by-products from Chinese bayberry processing.


Subject(s)
Antioxidants , Drosophila melanogaster , Myrica , Oxidative Stress , Wine , Animals , Female , Male , Anthocyanins/pharmacology , Antioxidants/pharmacology , Antioxidants/metabolism , Drosophila melanogaster/drug effects , Drosophila melanogaster/metabolism , Fermentation , Fruit/chemistry , Hydrogen Peroxide/metabolism , Longevity/drug effects , Myrica/chemistry , Oxidative Stress/drug effects , Wine/analysis
14.
PLoS One ; 19(9): e0302673, 2024.
Article in English | MEDLINE | ID: mdl-39264947

ABSTRACT

Mechanical stress is a measure of internal resistance exhibited by a body or material when external forces, such as compression, tension, bending, etc. are applied. The study of mechanical stress on health and aging is a continuously growing field, as major changes to the extracellular matrix and cell-to-cell adhesions can result in dramatic changes to tissue stiffness during aging and diseased conditions. For example, during normal aging, many tissues including the ovaries, skin, blood vessels, and heart exhibit increased stiffness, which can result in a significant reduction in function of that organ. As such, numerous model systems have recently emerged to study the impact of mechanical and physical stress on cell and tissue health, including cell-culture conditions with matrigels and other surfaces that alter substrate stiffness and ex vivo tissue models that can apply stress directly to organs like muscle or tendons. Here, we sought to develop a novel method in an in vivo model organism setting to study the impact of altering substrate stiffness on aging by changing the stiffness of solid agar medium used for growth of C. elegans. We found that greater substrate stiffness had limited effects on cellular health, gene expression, organismal health, stress resilience, and longevity. Overall, our study reveals that altering substrate stiffness of growth medium for C. elegans has only mild impact on animal health and longevity; however, these impacts were not nominal and open up important considerations for C. elegans biologists in standardizing agar medium choice for experimental assays.


Subject(s)
Caenorhabditis elegans , Longevity , Animals , Caenorhabditis elegans/physiology , Caenorhabditis elegans/growth & development , Stress, Mechanical , Culture Media
15.
Sci Rep ; 14(1): 21328, 2024 09 12.
Article in English | MEDLINE | ID: mdl-39266601

ABSTRACT

This study challenges historical paradigms using a large-scale integrated bioarchaeological approach, focusing on the female experience over the last 2,000 years in Milan, Italy. Specifically, 492 skeletons from the osteological collection of Milan were used to elucidate female survivorship and mortality by integrating bioarchaeological and paleopathological data, paleoepidemiological analyses, and historical contextualization. Findings revealed changes in female longevity, with a notable increase from Roman to contemporary eras, albeit plateauing in the Middle Ages/modern period. Significant sex-specific differences in mortality risk and survivorship were observed: females had higher mortality risk and lower survivorship in the Roman (first-fifth century AD) and Modern (16th-18th century AD) eras, but this trend reversed in the contemporary period (19th-20th century AD). Cultural and social factors negatively impacted female mortality in Roman and modern Milan, while others buffered it during the Middle Ages (sixth-15th century AD). This study underscored the importance of bioarchaeological inquiries in reconstructing the past, providing answers that may challenge historical assumptions and shedding light on how the interplay of cultural, social, and biological factors shaped the female experience across millennia.


Subject(s)
Mortality , Humans , Female , Italy/epidemiology , Adult , History, Medieval , History, 17th Century , History, 15th Century , Middle Aged , Mortality/trends , Mortality/history , History, 16th Century , Longevity , History, Ancient , History, 20th Century , History, 18th Century , Male , History, 19th Century , Aged , Survivorship , Archaeology , History, 21st Century
16.
Int J Mol Sci ; 25(17)2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39273401

ABSTRACT

Aging is an exceptionally complex process that depends on genetic, environmental, and lifestyle factors. Previous studies within the International HLA and Immunogenetics Workshop (IHIWS) component "Immunogenetics of Ageing" showed that longevity is associated with positive selection of HLA-DRB1*11- and DRB1*16-associated haplotypes, shown to be protective against diseases. Within the 18th IHIWS, we aimed to investigate the relevance of telomere length for successful aging and its association with classical HLAs. In total 957 individuals from Bulgaria, Turkey, Romania, and Poland in two age groups, elderly individuals (age 65-99 years) and ethnically matched young group (age 18-64 years), were investigated. The obtained results confirmed interpopulation differences in the distribution of HLA alleles, documented the lengths of telomeres in analyzed populations, and demonstrated significant associations of telomere length with aging as well as with the presence of some HLA class I or class II alleles. They suggest that telomere length assessment combined with HLA genotyping may help identify immunogenetic profiles associated with longevity. The associations between HLA and telomeres support the theory that HLA genes influence the aging process. However, further research is needed to clarify the biological basis of the observed relationships.


Subject(s)
HLA Antigens , Longevity , Humans , Longevity/genetics , Aged , Middle Aged , Male , Adult , Female , Aged, 80 and over , Adolescent , HLA Antigens/genetics , Young Adult , Telomere/genetics , Alleles , Telomere Homeostasis , Aging/genetics , Aging/immunology , Haplotypes
17.
Int J Mol Sci ; 25(17)2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39273603

ABSTRACT

Clerodendranthus spicatus (Thunb.) (Kidney tea) is a very distinctive ethnic herbal medicine in China. Its leaves are widely used as a healthy tea. Many previous studies have demonstrated its various longevity-promoting effects; however, the safety and specific health-promoting effects of Clerodendranthus spicatus (C. spicatus) as a dietary supplement remain unclear. In order to understand the effect of C. spicatus on the longevity of Caenorhabditis elegans (C. elegans), we evaluated its role in C. elegans; C. spicatus water extracts (CSw) were analyzed for the major components and the effects on C. elegans were investigated from physiological and biochemical to molecular levels; CSw contain significant phenolic components (primarily rosmarinic acid and eugenolinic acid) and flavonoids (primarily quercetin and isorhamnetin) and can increase the lifespan of C. elegans. Further investigations showed that CSw modulate stress resistance and lipid metabolism through influencing DAF-16/FoxO (DAF-16), Heat shock factor 1 (HSF-1), and Nuclear Hormone Receptor-49 (NHR-49) signalling pathways; CSw can improve the antioxidant and hypolipidemic activity of C. elegans and prolong the lifespan of C. elegans (with the best effect at low concentrations). Therefore, the recommended daily use of C. spicatus should be considered when consuming it as a healthy tea on a daily basis.


Subject(s)
Caenorhabditis elegans , Lipid Metabolism , Oxidative Stress , Plant Extracts , Animals , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/metabolism , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Lipid Metabolism/drug effects , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Longevity/drug effects , Signal Transduction/drug effects , Antioxidants/pharmacology , Water
18.
Cells ; 13(18)2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39329779

ABSTRACT

A characteristic feature of Alzheimer's disease (AD) is the formation of neuronal extracellular senile plaques composed of aggregates of fibrillar amyloid ß (Aß) peptides, with the Aß1-42 peptide being the most abundant species. These Aß peptides have been proposed to contribute to the pathophysiology of the disease; however, there are few tools available to test this hypothesis directly. In particular, there are no data that establish a dose-response relationship between Aß peptide expression level and disease. We have generated a panel of transgenic Caenorhabditis elegans strains expressing the human Aß1-42 peptide under the control of promoter regions of two pan-neuronal expressed genes, snb-1 and rgef-1. Phenotypic data show strong age-related defects in motility, subtle changes in chemotaxis, reduced median and maximum lifespan, changes in health span indicators, and impaired learning. The Aß1-42 expression level of these strains differed as a function of promoter identity and transgene copy number, and the timing and severity of phenotypes mediated by Aß1-42 were strongly positively correlated with expression level. The pan-neuronal expression of varying levels of human Aß1-42 in a nematode model provides a new tool to investigate the in vivo toxicity of neuronal Aß expression and the molecular and cellular mechanisms underlying AD progression in the absence of endogenous Aß peptides. More importantly, it allows direct quantitative testing of the dose-response relationship between neuronal Aß peptide expression and disease for the first time. These strains may also be used to develop screens for novel therapeutics to treat Alzheimer's disease.


Subject(s)
Amyloid beta-Peptides , Animals, Genetically Modified , Caenorhabditis elegans , Neurons , Phenotype , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/genetics , Amyloid beta-Peptides/metabolism , Animals , Neurons/metabolism , Neurons/pathology , Humans , Peptide Fragments/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/genetics , Longevity/genetics , Promoter Regions, Genetic/genetics , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics
19.
Int J Occup Med Environ Health ; 37(3): 335-350, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39221497

ABSTRACT

OBJECTIVES: The aim of this work is to initiate or revive a scientific discussion on the impact of professional life on the parameters of human lifespan. MATERIAL AND METHODS: Presented analysis is based on 8578 Polish elite or well-known person who died in 2001-2021. RESULTS: The results of the conducted analysis indicate that in the case of men the highest values of the median age at death were characteristic of freelancers (median [Me] ± quartile deviation [QD] 85.5±8.5 years), followed by scientists and academic teachers of the biological and medical specialty (Me±QD 84.0±7.5 years) and officers of power structures (Me±QD 83.5±8.5 years). Subsequently, the highest value of the median age at death was recorded for social activists (Me±QD 83.0±9.5 years), clergy (Me±QD 82.0±7.5 years) and scientists and academic teachers of specialties other than biological and medical (Me±QD 82.0±8.0 years). Significantly, at the very end of this list are athletes (Me±QD 77.0±9.0 years). Nevertheless, the results of the analysis confirm that professional athletes are characterized by higher median age at death compared to the general population. Analysis made only within athletes group demonstrated that the parameters of lifespan of athletes of endurance disciplines (Me±QD 78.0±8.0 years) are the most favorable compared to athletes of other disciplines, in particular in compare to team sports athletes (Me±QD 75.0±10.0 years) or combat sports athletes (Me±QD 75.0±7.1 years). CONCLUSIONS: What is new and innovative in this paper is comparing the lifespan characteristics of athletes in comparison to widely represented group of other professions with higher socio-economic status. Unexpectedly, the lifespan of athletes occurred to be lower than for fast all other analyzed occupational groups, except mainly of entertainment musicians. Finally, the results presented in this paper emphasize the need to analyze the lifespan characteristics of athletes in a broader scope than only in relation to the general population. Int J Occup Med Environ Health 2024;37(3):335-50.


Subject(s)
Athletes , Longevity , Humans , Poland/epidemiology , Male , Athletes/statistics & numerical data , Female , Middle Aged , Aged , Adult , Aged, 80 and over
20.
Am Nat ; 204(4): 315-326, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39326055

ABSTRACT

AbstractIn dimorphic vertebrates where males are larger than females, the energetic costs of producing and rearing sons can exceed those of daughters. In humans, differences in maternal energy intake suggest that sons require 10% and 7% more energy than daughters during pregnancy and lactation, respectively. Due to a trade-off between reproduction and somatic maintenance, having sons is expected to have a more pronounced detrimental impact on a mother's lifespan than having daughters. A limitation of previous studies investigating this hypothesis is that the increased mortality cost of having sons was assumed to affect all mothers equally. Using a dataset from a preindustrial Quebec population monitored over two centuries, we found that the number of sons decreased postmenopausal lifespan only in mothers experiencing high infant mortality. Our study highlights the importance of interindividual variation in environmental conditions and maternal health when studying effects of offspring sex on reproductive costs.


Subject(s)
Infant Mortality , Longevity , Female , Male , Humans , Quebec , Infant , History, 18th Century , History, 19th Century , Mothers , Sex Ratio , Adult , History, 17th Century , Middle Aged
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