Human Lifespan Research Articles

Scientific evidence of foods that improve the lifespan and healthspan of different organisms.

Age is a risk factor for numerous diseases. Although the development of modern medicine has greatly extended the human lifespan, the duration of relatively healthy old age, or 'healthspan', has not increased. Targeting the detrimental processes that can occur before the onset of age-related diseases can greatly improve health and lifespan. Healthspan is significantly affected by what, when and how much one eats. Dietary restriction, including calorie restriction, fasting or fasting-mimicking diets, to extend both lifespan and healthspan has recently attracted much attention. However, direct scientific evidence that consuming specific foods extends the lifespan and healthspan seems lacking. Here, we synthesized the results of recent studies on the lifespan and healthspan extension properties of foods and their phytochemicals in various organisms to confirm how far the scientific research on the effect of food on the lifespan has reached.

Convergent resistance to GABA receptor neurotoxins through plant-insect coevolution.

The molecular mechanisms of coevolution between plants and insects remain elusive. GABA receptors are targets of many neurotoxic terpenoids, which represent the most diverse array of natural products known. Over deep evolutionary time, as plant terpene synthases diversified in plants, so did plant terpenoid defence repertoires. Here we show that herbivorous insects and their predators evolved convergent amino acid changing substitutions in duplicated copies of the Resistance to dieldrin (Rdl) gene that encodes the GABA receptor, and that the evolution of duplicated Rdl and terpenoid-resistant GABA receptors is associated with the diversification of moths and butterflies. These same substitutions also evolved in pests exposed to synthetic insecticides that target the GABA receptor. We used in vivo genome editing in Drosophila melanogaster to evaluate the fitness effects of each putative resistance mutation and found that pleiotropy both facilitates and constrains the evolution of GABA receptor resistance. The same genetic changes that confer resistance to terpenoids across 300 Myr of insect evolution have re-evolved in response to synthetic analogues over one human lifespan.

Genetic strategies for sex-biased persistence of gut microbes across human life

Although compositional variation in the gut microbiome during human development has been extensively investigated, strain-resolved dynamic changes remain to be fully uncovered. In the current study, shotgun metagenomic sequencing data of 12,415 fecal microbiomes from healthy individuals are employed for strain-level tracking of gut microbiota members to elucidate its evolving biodiversity across the human life span. This detailed longitudinal meta-analysis reveals host sex-related persistence of strains belonging to common, maternally-inherited species, such as Bifidobacterium bifidum and Bifidobacterium longum subsp. longum. Comparative genome analyses, coupled with experiments including intimate interaction between microbes and human intestinal cells, show that specific bacterial glycosyl hydrolases related to host-glycan metabolism may contribute to more efficient colonization in females compared to males. These findings point to an intriguing ancient sex-specific host-microbe coevolution driving the selective persistence in women of key microbial taxa that may be vertically passed on to the next generation.

Unraveling Lifelong Brain Morphometric Dynamics: A Protocol for Systematic Review and Meta-Analysis in Healthy Neurodevelopment and Ageing.

A high incidence and prevalence of neurodegenerative diseases and neurodevelopmental disorders justify the necessity of well-defined criteria for diagnosing these pathologies from brain imaging findings. No easy-to-apply quantitative markers of abnormal brain development and ageing are available. We aim to find the characteristic features of non-pathological development and degeneration in distinct brain structures and to work out a precise descriptive model of brain morphometry in age groups. We will use four biomedical databases to acquire original peer-reviewed publications on brain structural changes occurring throughout the human life-span. Selected publications will be uploaded to Covidence systematic review software for automatic deduplication and blinded screening. Afterwards, we will manually review the titles, abstracts, and full texts to identify the papers matching eligibility criteria. The relevant data will be extracted to a 'Summary of findings' table. This will allow us to calculate the annual rate of change in the volume or thickness of brain structures and to model the lifelong dynamics in the morphometry data. Finally, we will adjust the loss of weight/thickness in specific brain areas to the total intracranial volume. The systematic review will synthesise knowledge on structural brain change across the life-span.

Smart Water Tank Level Detection

As the world around, us transforms and becomes more linked and digitalized, public water management is expected to provide in way. How far are we from achieving a true Smart Water Tank Level Detection, from cutting-edge technology to comfort, safety, reliability, and maintain. We notice that cleanliness of the surrounding area in Water Tank is also important because many people using by water stoaring tank, so how much west water is collected in the any other tank. As a result, we are implementing this approach and developing a green and complete water management city. Because of the day by day by many variant viruses in water and clean water is minimum available of sources, the smart water tank finder is primarily focused on human health, The human body will be affected, and the human life span will be reduced. So, by employing this system, the amount of human power necessary will be minimized, and you will be notified automatically on your mobile screen when a water tank needs to be disconnected supply or when an order is detected. Another sensor, ultrasonic sensor

COVID-19 and Brain Aging: What are the Implications of Immunosenescence?

The human lifespan is increasing, and mankind is aging. It is estimated that, until the year 2050, this population worldwide will reach 22% of the total world population. Along with aging, the human immunologic system changes, a process called immunosenescence or even inflammaging. The aging immune system increases mortality and morbidity in the elderly mainly because it loses its capacity to react against internal and external aggressions. There is a decrease in B and T lymphocytes and CD4+ lymphocytes lose the CD28 protein expression that is needed for costimulation, leading to reduced response to viral infections. This could be responsible for more deleterious consequences of coronavirus disease infection in the elderly. Besides that, the human brain ages, being more susceptible to damage and viral infections, such as COVID-19 infection. There are several pathways that could explain the susceptibility to the COVID-19 infection in the elderly brain, one of them is binding to ACE 2 receptors in cerebral cells through the spike protein. It has been reported that glial cells and neurons, in addition to endothelial and arterial smooth muscle cells in the brain, express the ACE 2 receptor, which would justify the neurological symptoms and consequences of the disease. This infection can have several clinical manifestations such as hemorrhagic stroke, delirium and long-term cognitive complaints, such as brain fog, polyneuropathies, short time memory complaints and insomnia. Although none of the studies could prove that there is a long-term neuronal damage, there are clinical sequelae that should be taken into account and more studies are necessary to know the consequences of the infection in the elderly brain.

Translational longevity medicine: a Swiss perspective in an ageing country.

Breakthroughs in medical research in the last century have led to a significant extension of the human lifespan, resulting in a shift towards an elderly population worldwide. Due to the ongoing progress of global development towards elevated standards of living, this study specifically examines Switzerland as a representative nation to explore the socioeconomic and healthcare ramifications associated with an ageing population, thereby highlighting the tangible impact experienced in this context. Beyond the exhaustion of pension funds and medical budgets, by reviewing the literature and analysing publicly available data, we observe a "Swiss Japanification". Old age is associated with late-life comorbidities and an increasing proportion of time spent in poor health. To address these problems, a paradigm shift in medical practice is needed to improve health rather than respond to existing diseases. Basic ageing research is gaining momentum to be translated into therapeutic interventions and provides machine learning tools driving longevity medicine. We propose that research focus on closing the translational gap between the molecular mechanisms of ageing and a more prevention-based medicine, which would help people age better and prevent late-life chronic diseases.

Electrochemical oxidation technique to pharmaceutical pollutants removal

Human progress in medical science and drug production has improved the growth process and increased human lifespan. Most of the drugs used are to control or prevent common human diseases. These drugs can be produced in different ways such as synthetic, chemical, biological, etc. On the other hand, pharmaceutical companies have a large volume of pharmaceutical effluents and wastewater that enters the environment and harms nature and human life. The main problems of entering the pharmaceutical effluent into the environmental cycle are the creation of drug resistance against the active substance of the drugs and the occurrence of abnormalities in the next generations. Therefore, the process of pharmaceutical wastewater treatment is used to reduce the level of pharmaceutical pollutants in order to enter the pharmaceutical wastewater into the environmental cycle. Until recently, filtration, passing through reverse osmosis and ion exchange resins, cleaning facilities, etc., have been various methods to remove pharmaceutical pollutants. Due to the low efficiency of the usual and old systems, the use of new methods has attracted more attention. In this article, the aim is to investigate the electrochemical oxidation method in order to remove the active ingredient of some commonly used drugs (aspirin, atorvastatin, metformin, metronidazole and ibuprofen) from the wastewater of pharmaceuticals. Therefore, in order to observe the initial conditions of the samples, a cyclic voltammetry diagram with a scanning rate of 100 mV/s has been performed. Next, by using the chronoamperometry process and applying a constant potential, the desired drugs were subjected to the electrochemical process of oxidation.As a result, the re-examined samples were subjected to cyclic voltammetry test to determine the conditions of sample oxidation peaks as well as the removal efficiency of the samples by examining the surface under the initial and final voltammetry graph. The results indicate that this method for removing selected drugs has a high removal efficiency of about 70% and 100% for atorvastatin samples. Therefore, this method is accurate, reproducible (RSD 2%), efficient, easy and economical and can be used in drug manufacturing industries. This method is used in a wide range of drug concentration. This means that by increasing the concentration of the drug, without the need to change the equipment used and the applied potential, by spending more time in the oxidation process, it is possible to remove very high amounts of the drug (more than 1000 ppm).

No One is Immune to Infertility

Both primary and secondary infertility affects millions of person’s world over. There are several factors that can contribute to infertility in women and men however about 1 in 5 cases of infertility are identified as unexplained. There’s a time frame to fertility in human life span; child bearing age is defined in females but not in males in general. Infertility has significant negative social impacts particularly on women. Infertility is regarded as a negative force in population dynamics because there is no biological replacement, and the continuation of human society. Infertile couples might experience social and psychological distress such as depression, anxiety, social isolation, and sexual dysfunction. Infertile couples suffer from an impaired health-related quality of life. Women in particular are at greater risk of violence, divorce, social stigma, emotional stress, depression, anxiety and low self-esteem. In women, cause of infertility can include endometriosis, uterine fibroids and thyroid disease. Men with fertility problems may have a low sperm count or low testosterone. The risk of infertility increases with age.

Global branches and local states of the human gut microbiome define associations with environmental and intrinsic factors

The gut microbiome is important for human health, yet modulation requires more insight into inter-individual variation. Here, we explored latent structures of the human gut microbiome across the human lifespan, applying partitioning, pseudotime, and ordination approaches to >35,000 samples. Specifically, three major gut microbiome branches were identified, within which multiple partitions were observed in adulthood, with differential abundances of species along branches. Different compositions and metabolic functions characterized the branches’ tips, reflecting ecological differences. An unsupervised network analysis from longitudinal data from 745 individuals showed that partitions exhibited connected gut microbiome states rather than over-partitioning. Stability in the Bacteroides-enriched branch was associated with specific ratios of Faecalibacterium:Bacteroides. We also showed that associations with factors (intrinsic and extrinsic) could be generic, branch- or partition-specific. Our ecological framework for cross-sectional and longitudinal data allows a better understanding of overall variation in the human gut microbiome and disentangles factors associated with specific configurations.

1739-P: Ontogeny of Bihormonal Islet Cells within the Human Pancreas

Bi-hormonal islet endocrine cells have been proposed to represent an intermediate state during cellular trans-differentiation, enabling plasticity of islet beta-cells in response to metabolic stress. Beta-cell plasticity and regenerative capacity are thought to decrease with age. We investigated bi-hormonal islet endocrine cell populations present throughout the human lifespan between 11 days to 79 years of age. Immunohistochemical staining was performed on paraffin-embedded sections of pancreata from 24 individuals without diabetes for insulin, glucagon, and somatostatin. The sections were imaged with epifluorescence microscopy, and hormone-positive cells were manually counted using ImageJ software considering cells where more than 50% of the area was immunopositive. The mean proportional presence of glucagon-, insulin-, and somatostatin-immunopositive cells within islets was 28.8%, 65.1%, and 13.8% respectively, similar to previous reports for human islets. The relative presence of alpha- and beta-cells increased, and for delta-cells decreased, with advancing age. With respect to bi-hormonal cells the overall presence of glucagon+/insulin+ cells was 3.3%, for somatostatin+/insulin+ cells was 2.4%, and for glucagon+/somatostatin+ cells was 1.7% relative to total islet cell number. The proportion of glucagon+/somatostatin+ cells in the islets of female individuals, in particular, diminished with age (r2=0.43), whereas the other cell types remained largely constant with age in both sexes. The prevalence of tri-hormonal islet cells was low (0.45%). The findings suggest that bi-hormonal islet cells are present within human pancreatic islets throughout life, perhaps reflecting an ongoing potential for endocrine cell plasticity. Disclosure J.Hahm: None. J.A.Fernandez andrade: None. E.Arany: None. D.J.Hill: None. Funding Lawson Foundation

Telomere length dynamics across the human lifespan: A systematic review and meta-analysis

This systematic review aims to evaluate the dynamics of telomere length (TL), a biomarker used to assess biological aging and disease states, across the human lifespan and the impact of methodological and disease factors. Following a pre-registered protocol, studies on TL published before 2022 were collected from PubMed and Web of Science and screened based on pre-defined criteria. Summary statistics were extracted from all studies. Correlation between TL and age was used as the effect size and corrected for age-range restriction. Random-effects models were used to pool effect sizes. Impact of health status (healthy, cardiovascular disease, cancer, mental health, general population) and methodological factors was examined through meta-regression. 279 cross-sectional studies across 149,527 subjects (age 0-112years) and 50 longitudinal studies across 20,351 subjects (age 0-94years) were included. For cross-sectional studies, the pooled corrected correlation was -0.17 (95%CI: -0.21 to -0.13). The correlation weakened with increasing chronological age (β=0.003, p=.007). Health status did not moderate the correlation. TL measured in saliva (k=14) had a weaker correlation with age than TL measured in blood leukocytes (k=218; β=0.266, p=.004). Magnetic bead DNA extraction method (k=13) moderated the relationship between TL and age compared with salting out (k=57) methods (β=0.412, p<0.001). For longitudinal studies, the yearly z-score change rate of TL ranged from -0.74 to 0.36, with a median change of -0.06. TL decreases with age at a decelerating rate in older ages. Cell type and DNA extraction method may moderate the correlation between TL and age.

KIR-HLA interactions extend human CD8+ T cell lifespan in vivo.

BACKGROUNDThere is increasing evidence, in transgenic mice and in vitro, that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses. Furthermore, we have previously shown that iKIRs are an important determinant of T cell-mediated control of chronic viral infection and that these results are consistent with an increase in the CD8+ T cell lifespan due to iKIR-ligand interactions. Here, we tested this prediction and investigated whether iKIRs affect T cell lifespan in humans in vivo.METHODSWe used stable isotope labeling with deuterated water to quantify memory CD8+ T cell survival in healthy individuals and patients with chronic viral infections.RESULTSWe showed that an individual's iKIR-ligand genotype was a significant determinant of CD8+ T cell lifespan: in individuals with 2 iKIR-ligand gene pairs, memory CD8+ T cells survived, on average, for 125 days; in individuals with 4 iKIR-ligand gene pairs, the memory CD8+ T cell lifespan doubled to 250 days. Additionally, we showed that this survival advantage was independent of iKIR expression by the T cell of interest and, further, that the iKIR-ligand genotype altered the CD8+ and CD4+ T cell immune aging phenotype.CONCLUSIONSTogether, these data reveal an unexpectedly large effect of iKIR genotype on T cell survival.FUNDINGWellcome Trust; Medical Research Council; EU Horizon 2020; EU FP7; Leukemia and Lymphoma Research; National Institute of Health Research (NIHR) Imperial Biomedical Research Centre; Imperial College Research Fellowship; National Institutes of Health; Jefferiss Trust.

İleri Yaş ve Engelli Turizmi Yapılarının Sürdürülebilirlik Kavramı Özelinde İrdelenmesi

Environmental problems and heavy living conditions, which are the result of industrialization and intense urbanization, affect health negatively. In addition, developments in the level of welfare and health have extended the human lifespan and increased the proportion of the elderly population. These developments, combined with people’s efforts to be physically and mentally well, have started a movement to regain their health, and over time, the concept of health tourism has emerged. Buildings for health tourism are mixed-function that includes tourism activities as well as treatment units. In this article, a schema has been created by considering the sustainability concept of the buildings that serve the elderly and disabled tourism, which have a place under the title of health tourism. With the evaluations to be made on the schema obtained within the scope of this study, it is aimed to ensure the development of the facilities and suggestions are forth.

Healthcare Service Efficiency: An Empirical Study on Healthcare Capacity in Various Counties and Cities in Taiwan.

As human lifespan increases and the need for elderly care grows, the demand for healthcare services and its associated costs have surged, causing a decline in the operational efficiency of universal healthcare. This has created an imbalance in medical services across different regions, posing a long-standing challenge for the public. To address this issue, strategies to enhance the capacity, efficiency, and quality of healthcare services in various regions must be developed. The appropriate allocation of medical resources is a fundamental requirement for countries to establish a robust healthcare system. This empirical study utilized data envelopment analysis (DEA) to evaluate the efficiency of medical service capacity and identify potential improvement strategies for counties and cities in Taiwan during the period from 2015 to 2020. The results of this study show that (1) the annual average efficiency of medical service capacity in Taiwan is approximately 90%, indicating that there is still room for a 10% improvement; (2) among the six municipalities, only Taipei City has sufficient healthcare capacity, whereas the efficiency of the remaining municipalities needs improvement; and (3) most counties and cities demonstrated increasing returns to scale, indicating a need to scale up the capacity of medical services as appropriate. Based on the findings of this study, it is recommended that medical personnel be increased accordingly to balance the workload, a favorable working environment be provided to stabilize the medical workforce, and urban-rural medical disparities be balanced to improve service quality and reduce cross-regional health services. These recommendations are expected to provide a reference for society as a whole to promote and enhance public health policies, leading to a continual improvement of the quality of medical services.

Analysis of the microglia transcriptome across the human lifespan using single cell RNA sequencing

BackgroundMicroglia are tissue resident macrophages with a wide range of critically important functions in central nervous system development and homeostasis.MethodIn this study, we aimed to characterize the transcriptional landscape of ex vivo human microglia across different developmental ages using cells derived from pre-natal, pediatric, adolescent, and adult brain samples. We further confirmed our transcriptional observations using ELISA and RNAscope.ResultsWe showed that pre-natal microglia have a distinct transcriptional and regulatory signature relative to their post-natal counterparts that includes an upregulation of phagocytic pathways. We confirmed upregulation of CD36, a positive regulator of phagocytosis, in pre-natal samples compared to adult samples in situ. Moreover, we showed adult microglia have more pro-inflammatory signature compared to microglia from other developmental ages. We indicated that adult microglia are more immune responsive by secreting increased levels of pro-inflammatory cytokines in response to LPS treatment compared to the pre-natal microglia. We further validated in situ up-regulation of IL18 and CXCR4 in human adult brain section compared to the pre-natal brain section. Finally, trajectory analysis indicated that the transcriptional signatures adopted by microglia throughout development are in response to a changing brain microenvironment and do not reflect predetermined developmental states.ConclusionIn all, this study provides unique insight into the development of human microglia and a useful reference for understanding microglial contribution to developmental and age-related human disease.

FOXM1: Functional Roles of FOXM1 in Non-Malignant Diseases.

Forkhead box (FOX) proteins are a wing-like helix family of transcription factors in the DNA-binding region. By mediating the activation and inhibition of transcription and interactions with all kinds of transcriptional co-regulators (MuvB complexes, STAT3, β-catenin, etc.), they play significant roles in carbohydrate and fat metabolism, biological aging and immune regulation, development, and diseases in mammals. Recent studies have focused on translating these essential findings into clinical applications in order to improve quality of life, investigating areas such as diabetes, inflammation, and pulmonary fibrosis, and increase human lifespan. Early studies have shown that forkhead box M1 (FOXM1) functions as a key gene in pathological processes in multiple diseases by regulating genes related to proliferation, the cell cycle, migration, and apoptosis and genes related to diagnosis, therapy, and injury repair. Although FOXM1 has long been studied in relation to human diseases, its role needs to be elaborated on. FOXM1 expression is involved in the development or repair of multiple diseases, including pulmonary fibrosis, pneumonia, diabetes, liver injury repair, adrenal lesions, vascular diseases, brain diseases, arthritis, myasthenia gravis, and psoriasis. The complex mechanisms involve multiple signaling pathways, such as WNT/β-catenin, STAT3/FOXM1/GLUT1, c-Myc/FOXM1, FOXM1/SIRT4/NF-κB, and FOXM1/SEMA3C/NRP2/Hedgehog. This paper reviews the key roles and functions of FOXM1 in kidney, vascular, lung, brain, bone, heart, skin, and blood vessel diseases to elucidate the role of FOXM1 in the development and progression of human non-malignant diseases and makes suggestions for further research.

Age effects in second language acquisition: Expanding the emergentist account

In 2005, Science magazine designated the problem of accounting for difficulties in L2 (second language) learning as one of the 125 outstanding challenges facing scientific research. A maturationally-based sensitive period has long been the favorite explanation for why ultimate foreign language attainment declines with age-of-acquisition. However, no genetic or neurobiological mechanisms for limiting language learning have yet been identified. At the same time, we know that cognitive, social, and motivational factors change in complex ways across the human lifespan. Emergentist theory provides a framework for relating these changes to variation in the success of L2 learning. The great variability in patterns of learning, attainment, and loss across ages, social groups, and linguistic levels provides the core motivation for the emergentist approach. Our synthesis incorporates three groups of factors which change systematically with age: environmental supports, cognitive abilities, and motivation for language learning. This extended emergentist account explains why and when second language succeeds for some children and adults and fails for others.

Discovering Biological Mechanisms of Exceptional Human Health Span and Life Span.

Humans age at different rates and families with exceptional longevity provide an opportunity to understand why some people age slower than others. Unique features exhibited by centenarians include a family history of extended life span, compression of morbidity with resultant extension of health span, and longevity-associated biomarker profiles. These biomarkers, including low-circulating insulin-like growth factor 1 (IGF-1) and elevated high-density lipoprotein (HDL) cholesterol levels, are associated with functional genotypes that are enriched in centenarians, suggesting that they may be causative for longevity. While not all genetic discoveries from centenarians have been validated, in part due to exceptional life span being a rare phenotype in the general population, the APOE2 and FOXO3a genotypes have been confirmed in a number of populations with exceptional longevity. However, life span is now recognized as a complex trait and genetic research methods to study longevity are rapidly extending beyond classical Mendelian genetics to polygenic inheritance methodologies. Moreover, newer approaches are suggesting that pathways that have been recognized for decades to control life span in animals may also regulate life span in humans. These discoveries led to strategic development of therapeutics that may delay aging and prolong health span.

The application of exosomes in the early diagnosis and treatment of osteoarthritis.

With the increase in human lifespan and the aggravation of global aging, the incidence of osteoarthritis (OA) is increasing annually. To better manage and control the progression of OA, prompt diagnosis and treatment for early-stage OA are important. However, a sensitive diagnostic modality and therapy for early OA have not been well developed. The exosome is a class of extracellular vesicles containing bioactive substances, that can be delivered directly from original cells to neighboring cells to modulate cellular activities through intercellular communication. In recent years, exosomes have been considered important in the early diagnosis and treatment of OA. Synovial fluid exosome and its encapsulated substances, e.g., microRNA, lncRNA, and proteins, can not only distinguish OA stages but also prevent the progression of OA by directly targeting cartilage or indirectly modulating the immune microenvironment in the joints. In this mini-review, we include recent studies on the diagnostic and therapeutic modalities of exosomes and hope to provide a new direction for the early diagnosis and treatment of OA disease in the future.