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

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.

Impact of maternal protein restriction on the proteomic landscape of male rat lungs across the lifespan.

The developmental origins of healthy and disease (DOHaD) concept has demonstrated a higher rate of chronic diseases in the adult population of individuals whose mothers experienced severe maternal protein restriction (MPR). Using proteomic and in silico analyses, we investigated the lung proteomic profile of young and aged rats exposed to MPR during pregnancy and lactation. Our results demonstrated that MPR lead to structural and immune system pathways changes, and this outcome is coupled with a rise in the PI3k-AKT-mTOR signaling pathway, with increased MMP-2 activity, and CD8 expression in the early life, with long-term effects with aging. This led to the identification of commonly or inversely differentially expressed targets in early life and aging, revealing dysregulated pathways related to the immune system, stress, muscle contraction, tight junctions, and hemostasis. We identified three miRNAs (miR-378a-3p, miR-378a-5p, let-7a-5p) that regulate four proteins (ACTN4, PPIA, HSPA5, CALM1) as probable epigenetic lung marks generated by MPR. In conclusion, MPR impacts the lungs early in life, increasing the possibility of long-lasting negative outcomes for respiratory disorders in the offspring.

Defying "IL-11ness" by inhibiting inflammation: Strategy for health and longevity.

Organismal aging involves several hallmark pathways, including chronic inflammation and metabolic dysfunction. However, the origin of age-related inflammation is incompletely understood. In a recent study published in Nature,1 Widjaja et al. show that blocking the age-related increase in IL-11 restores immune-metabolic homeostasis and extends healthspan and lifespan in mice.

Unveiling the female experience through adult mortality and survivorship in Milan over the last 2000 years.

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.

The d3GHR carrier epigenome in Druze clan longevity.

The Druze are a distinct group known for their close community, traditions, and consanguineous marriages, dating back to the eleventh century. This practice has led to unique genetic variations, impacting both pathology and gene-associated phenotypes. Some Druze clans, particularly those with exceptional long-lived family heads (ELLI), attracted attention. Given that the bulk of these ELLI were men, the d3GHR polymorphism was the first obvious possibility. Among the 73 clan members, 8.2% carried the d3GHR isoform, with nearly 11% being males. There was a significant age-related increase (p = 0.04) in this isoform among males, leading to examination of potential environmental mediators affecting gene regulation among these carriers during life (namely epigenetic). We focused on DNA methylation due to its crucial role in gene regulation, development, and disease progression. We analyzed DNA samples from 14 clan members with different GHR genotypes, finding a significant (p < 0.05) negative correlation between DNA methylation levels and age. Employing a biological age clock, we observed a significant + 4.229 years favoring the d3GHR group over the WT and heterozygous groups. In conclusion, this study highlights the advantage of d3GHR carriers among this unique Druze clan and underscores the importance of genotype-environment interaction in epigenetic regulation and its impact on health.

Telomere Length, HLA, and Longevity-Results from a Multicenter Study.

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.

Clerodendranthus spicatus (Thunb.) Water Extracts Reduce Lipid Accumulation and Oxidative Stress in the Caenorhabditis elegans.

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.

Fundamental equations linking methylation dynamics to maximum lifespan in mammals.

We describe a framework that addresses concern that the rate of change in any aging biomarker displays a trivial inverse relation with maximum lifespan. We apply this framework to methylation data from the Mammalian Methylation Consortium. We study the relationship of lifespan with the average rate of change in methylation (AROCM) from two datasets: one with 90 dog breeds and the other with 125 mammalian species. After examining 54 chromatin states, we conclude three key findings: First, a reciprocal relationship exists between the AROCM in bivalent promoter regions and maximum mammalian lifespan: AROCM ∝ 1/MaxLifespan. Second, the correlation between average methylation and age bears no relation to maximum lifespan, Cor(Methyl,Age) ⊥ MaxLifespan. Third, the rate of methylation change in young animals is related to that in old animals: Young animals' AROCM ∝ Old AROCM. These findings critically hinge on the chromatin context, as different results emerge in other chromatin contexts.

Longevity of Polish top-class athletes compared to other social elites and well-known people in the years 2001-2021.

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.

Growth on stiffer substrates impacts animal health and longevity in C. elegans.

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.

Hunt for longevity drugs gets new life.

Decades-old project has new funding and a new set of compounds to test.

The inflammaging clock strikes IL-11!

Chronic inflammation is considered a hallmark of aging. In a recent issue of Nature, Widjaja et al. examined genetic and pharmacologic inhibition of interleukin (IL)-11 on aging pathology and found that inhibiting IL-11 signaling increases lifespan and healthspan in mice.

Spatial cognitive ability is associated with longevity in food-caching chickadees.

Cognitive abilities are hypothesized to affect survival and life span in nonhuman animals. However, most tests of this hypothesis have relied on interspecific comparisons of indirect measures of cognitive ability, such as brain size. We present direct evidence that individual variation in cognitive abilities is associated with differences in life span in a wild food caching bird. We measured the spatial cognitive abilities and tracked the life span of 227 mountain chickadees (Poecile gambeli) in their natural environment and found that individuals with better spatial learning and memory abilities involved in food caching lived longer. These results confirm that enhanced cognitive abilities can be associated with longer life in wild animals and that selection on cognitive abilities can lead to increased life span.

Impact of diet and bacterial supplementation regimes on Orius strigicollis microbiota and life history performance.

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.

Protective effects of Chinese bayberry pomace wine against oxidative stress on Drosophila melanogaster.

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.

Low methyl-esterified ginseng homogalacturonan pectins promote longevity of Caenorhabditis elegans via impairing insulin/IGF-1 signalling.

Panax ginseng C. A. Meyer (ginseng) is a medicinal plant widely used for promoting longevity. Recently, homogalacturonan (HG) domain-rich pectins purified from some plants have been reported to have anti-aging-related activities, leading us to explore the longevity-promoting activity of the HG pectins from ginseng. In this study, we discovered that two of low methyl-esterified ginseng HG pectins (named as WGPA-2-HG and WGPA-3-HG), whose degree of methyl-esterification (DM) was 16 % and 8 % respectively, promoted longevity in Caenorhabditis elegans. Results showed that WGPA-2-HG/WGPA-3-HG impaired insulin/insulin-like growth factor 1 (IGF-1) signalling (IIS) pathway, thereby increasing the nuclear accumulation of transcription factors SKN-1/Nrf2 and DAF-16/FOXO and enhancing the expression of relevant anti-aging genes. BLI and ITC analysis showed that the insulin-receptor binding, the first step to activate IIS pathway, was impeded by the engagement of WGPA-2-HG/WGPA-3-HG with insulin. By chemical modifications, we found that high methyl-esterification of WGPA-2-HG/WGPA-3-HG was detrimental for their longevity-promoting activity. These findings provided novel insight into the precise molecular mechanism for the longevity-promoting effect of ginseng pectins, and suggested a potential to utilize the ginseng HG pectins with appropriate DM values as natural nutrients for increasing human longevity.

Can formal home and community-based care substitute informal care? Evidence from Chinese Longitudinal Healthy Longevity Survey.

BACKGROUND: Formal home and community-based care are often considered as the preferable option to institutional care, offering older individuals the convenience of receiving care in their homes. Although research has found that these services may alleviate the burden on informal caregivers, there is a lack of research on which specific types of formal home and community-based care influence informal care provision. METHODS: Employing fixed-effects and quantile regression models, this study seeks to explore the effects that various formal home and community-based care services have on reducing the burden of informal care. This study draws data from the Chinese Longitudinal Healthy Longevity Survey 2005, 2008, 2011, 2014, and 2018. RESULTS: Our findings indicate that two types of formal care substantially influence the provision of informal care. The availability of daily living assistance services correlates with reduced informal caregiving hours, especially for those with extensive care needs. The availability of community-based health care services is linked to a reduction in the direct expenses incurred from informal caregiving, especially for those incurring greater direct caregiving costs. These effects are more prominent among urban residents. Other services, such as mental health support and legal advice services, do not demonstrate significant effects on reducing informal care hours and costs. CONCLUSIONS: Daily living assistance and community-based health care services play a crucial role in benefiting informal caregivers. It is important to prioritize the expansion of these services, especially among those with greater care needs.

Cross-sectional and longitudinal analysis of health-related quality of life (HRQoL) in senior and geriatric dogs.

Advancements in veterinary medicine have resulted in increased life spans for dogs, necessitating a better understanding of quality of life for older dogs. This study aimed to evaluate quality of life (QoL) progression and its potential association with mortality in senior and geriatric dogs. The Canine Owner-Reported Quality of Life Questionnaire (CORQ), consisting of 17 questions across four domains (vitality, companionship, pain, and mobility) was employed. Higher scores indicated better quality of life, with 7 as the highest potential score for each question. In a cross-sectional analysis including 92 dogs, we found an inverse correlation between overall CORQ (and all domain scores) and fractional lifespan. The domain of vitality demonstrated the lowest scores, while companionship exhibited the highest. A longitudinal analysis, including 34 dogs, revealed that when dogs reach the geriatric stage (100% of their calculated lifespan), their expected overall CORQ is 5.95 out of 7, and dogs are expected to have a monthly decline of 0.05 units in the score. Cox proportional hazard analysis demonstrated a significant association between overall CORQ scores and mortality, with dogs scoring below 5.35 being at a higher risk of mortality. This study underscores the association between aging, declining quality of life, and increased mortality risk in aging dogs.

Modelling the age distribution of longevity leaders.

Human longevity leaders with remarkably long lifespan play a crucial role in the advancement of longevity research. In this paper, we propose a stochastic model to describe the evolution of the age of the oldest person in the world by a Markov process, in which we assume that the births of the individuals follow a Poisson process with increasing intensity, lifespans of individuals are independent and can be characterized by a gamma-Gompertz distribution with time-dependent parameters. We utilize a dataset of the world's oldest person title holders since 1955, and we compute the maximum likelihood estimate for the parameters iteratively by numerical integration. Based on our preliminary estimates, the model provides a good fit to the data and shows that the age of the oldest person alive increases over time in the future. The estimated parameters enable us to describe the distribution of the age of the record holder process at a future time point.