Gerontology Research Articles

Comprehensive gut microbiota composition and microbial interactions among the three age groups.

There is a growing interest in studying the microbiota associated with aging by integrating multiple longevity researches while minimizing the influence of confounding factors. Here, we reprocessed metagenomic sequencing data from four different aging research studies and evaluated potential confounding factors in order to minimize the batch effect. Subsequently, we detected the diversity and abundance of the gut microbiome in three different age cohorts. Out of 1053 different bacteria species, only four showed substantial depletion across different age groups: Ligilactobacillus ruminis, Turicibacter sp. H121, Blautia massiliensis, and Anaerostipes hadrus. Archaea accumulated more in young individuals compared to elderly and centenarians. Candida albicans was more prevalent in centenarians, but Nakaseomyces glabratus (also known as Candida glabrata) was more common in elderly adults. Shuimuvirus IME207 showed a significant increase in centenarians compared to both control groups. In addition, we utilized a Fisher's exact test to investigate topological properties of differentially abundant microbiota in the co-occurrence network of each age group. Microbial signatures specific to different age stages were identified based on the condition: the reads showing differential abundance were higher compared to the other age groups. Lastly, we selected Methanosarcina sp. Kolksee for the Y group, Prevotella copri for the E group and Shuimuvirus IME207 for the C group as representatives of age-related characteristics to study how their interactions change during the aging process. Our results provide crucial insights into the gut microbiome's ecological dynamics in relation to the aging process.

Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity.

The recent unprecedented progress in ageing research and drug discovery brings together fundamental research and clinical applications to advance the goal of promoting healthy longevity in the human population. We, from the gathering at the Aging Research and Drug Discovery Meeting in 2023, summarised the latest developments in healthspan biotechnology, with a particular emphasis on artificial intelligence (AI), biomarkers and clocks, geroscience, and clinical trials and interventions for healthy longevity. Moreover, we provide an overview of academic research and the biotech industry focused on targeting ageing as the root of age-related diseases to combat multimorbidity and extend healthspan. We propose that the integration of generative AI, cutting-edge biological technology, and longevity medicine is essential for extending the productive and healthy human lifespan.

Telomere length and cognitive function among middle-aged and older participants from communities underrepresented in aging research: A preliminary study.

Accelerated biological aging is a plausible and modifiable determinant of dementia burden facing minoritized communities, but is not well-studied in these historically underrepresented populations. Our objective was to preliminarily characterize relationships between telomere length and cognitive health among American Indian/Alaska Native (AI/AN) and Black/African American (B/AA) middle-aged and older adults. This study included data on telomere length and cognitive test performance from 187 participants, enrolled in one of two community-based cognitive aging cohorts and who identified their primary race as AI/AN or B/AA. Nested multivariable regression models revealed preliminary evidence for associations between telomere length and cognitive performance, and these associations were partially independent of chronological age. Small sample size limited estimate precision, however, findings suggest future work on telomere length and cognitive health in underrepresented populations at high risk for dementia is feasible and valuable as a foundation for social and behavioral intervention research.

Genomic instability and genetic heterogeneity in aging: insights from clonal hematopoiesis (CHIP), monoclonal gammopathy (MGUS), and monoclonal B-cell lymphocytosis (MBL).

Aging is a multifaceted process characterized by a gradual decline in physiological function and increased susceptibility to a range of chronic diseases. Among the molecular and cellular mechanisms driving aging, genomic instability is a fundamental hallmark, contributing to increased mutation load and genetic heterogeneity within cellular populations. This review explores the role of genomic instability and genetic heterogeneity in aging in the hematopoietic system, with a particular focus on clonal hematopoiesis of indeterminate potential (CHIP), monoclonal gammopathy of undetermined significance (MGUS), and monoclonal B-cell lymphocytosis (MBL) as biomarkers. CHIP involves the clonal expansion of hematopoietic stem cells with somatic mutations. In contrast, MGUS is characterized by the presence of clonal plasma cells producing monoclonal immunoglobulins, while MBL is characterized by clonal proliferation of B cells. These conditions are prevalent in the aging population and serve as measurable indicators of underlying genomic instability. Studying these entities offers valuable insights into the mechanisms by which somatic mutations accumulate and drive clonal evolution in the hematopoietic system, providing a deeper understanding of how aging impacts cellular and tissue homeostasis. In summary, the hematopoietic system serves as a powerful model for investigating the interplay between genomic instability and aging. Incorporating age-related hematological conditions into aging research, alongside other biomarkers such as epigenetic clocks, can enhance the precision and predictive power of biological age assessments. These biomarkers provide a comprehensive view of the aging process, facilitating the early detection of age-related diseases and hopefully enabling personalized healthcare strategies.

Evaluating facial dermis aging in healthy Caucasian females with LC-OCT and deep learning

Recent advancements in high-resolution imaging have significantly improved our understanding of microstructural changes in the skin and their relationship to the aging process. Line Field Confocal Optical Coherence Tomography (LC-OCT) provides detailed 3D insights into various skin layers, including the papillary dermis and its fibrous network. In this study, a deep learning model utilizing a 3D ResNet-18 network was trained to predict chronological age from LC-OCT images of 100 healthy Caucasian female volunteers, aged 20 to 70 years. The AI-based protocol focused on regions of interest delineated between the segmented dermal-epidermal junction and the superficial dermis, exploiting complex patterns within the collagen network for age prediction. The model achieved a mean absolute error of 4.2 years and exhibited a Pearson correlation coefficient of 0.937 with actual ages. Furthermore, there was a notable correlation (r = 0.87) between quantified clinical scoring, encompassing parameters such as firmness, elasticity, density, and wrinkle appearance, and the ages predicted by deep learning model. This strong correlation underscores how integrating emerging imaging technologies with deep learning can accelerate aging research and deepen our understanding of how alterations in skin microstructure are related to visible signs of aging.

Perspective: leveraging review protocols to advance implementation science in support of older adults' health equity.

Globally, there has been an increasing call for dissemination and implementation science to improve the health equity of older adults. However, improving the health equity of older adults requires methods that allow for an in-depth understanding of the existing research. While the value of review articles is widely recognized, the value of publishing review protocols is an emerging paradigm with great potential to advance implementation science and aging research. In this article, we propose that prior to review articles, review protocols are necessary as they provide a clear and comprehensive search strategy, which greatly enhances the quality and rigor of reviews. More specifically, we argue that review protocols are indispensable because they support: (1) a clearly defined and comprehensive search methodology; (2) reviewer feedback to mitigate potential issues; and (3) registration to reduce risk of research replication. Additionally, we propose three strategies to accelerate review protocols in implementation science to support older adults' health equity.

Noen nye funn av østlige belter og remutstyr fra sen vikingtid og tidlig middelalder i Norge

While belts and belt accessories have been a relatively minor theme for Viking Age research in Norway so far, unlike for instance in Sweden, new finds are changing the situation. This article deals with a particular type of strap accessories, namely so-called “oriental” mounts made from copper alloy, and originally produced mainly in present-day Russia and Ukraine. The author knows 26 such finds, most of them consisting of single mounts, and all of them resulting from metal-detecting. A number of finds stem from Northern Norway, where they seem, at least partially, to be another aspect of the already well-studied Eastern finds there. The majority of the new finds, however, have come to light in inland areas of eastern Norway. The latter area, in earlier times called “The Uplands” (Opplandene), seems to have had close connections both to Sweden and to areas further east in this period, as witnessed both by archaeological and written sources. It is suggested that the recent finds of “oriental” mounts represent, directly or indirectly, warriors that had spent time in the druzhinas of Ancient Rus’ rulers.

The Effects of APOE Alleles, Cognitive Activities, and Social Activities on Cognitive Decline in African Americans.

Older African Americans are among the fastest growing populations, yet are underrepresented in studies examining risk factors related to decline. The present study examines whether biological factors (APOE alleles) interact with behavioral factors including cognitive activities (e.g., reading, playing games) and social activities (e.g., participating in social groups) to predict cognitive decline in African Americans. 734 African American adults from the Minority Aging Research Study (MARS), aged 65 and older (with no known dementia at the time of enrollment) underwent annual cognitive testing for up to 10 years. At baseline, APOE status was determined and participants reported their frequency of participation in social and cognitive activities. Structural equation modelling was used to examine the effects of APOE, cognitive activities, and social activities on cognitive decline, and their interaction effects over a ten-year period. The number of APOE alleles had an effect on cognitive decline, such that a greater number of APOE4 alleles was associated with greater cognitive decline, whereas a greater number of APOE2 alleles was associated with less cognitive decline. Cognitive and social activities did not interact with APOE count to predict cognitive decline, however, APOE4 and social activities had additive, independent effects on cognitive decline. Results replicate prior findings linking APOE4 to cognitive decline and highlight the importance of APOE2 and social activities in delaying cognitive decline in African Americans.

Ischemic Stroke and the Biological Hallmarks of Aging.

With the advent of an aging population, the study of aging and related research has been increasingly prominent, focusing on how to fully understand and delay aging-a key concern for contemporary medical professionals. Stroke is an acute focal neurological deficit. Globally, ischemic stroke accounts for only 60-70% of all strokes, meanwhile, it is the second leading cause of death. With the introduction of the concept of biomarkers of ageing, the research of ischemic stroke or acute brain injury in relation to these biomarkers has remained fragmented. In this review, we aim to consolidate the current evidence, highlighting the intricate relationship between ischemic stroke and aging-related hallmarks during its occurrence. By providing a comprehensive overview, we hope to offer researchers a broader perspective on how acute injury mechanisms intertwine with aging. We hope to present a new viewpoint and a more complete evaluation framework for future research and exploration in the field of aging.

Mitochondrial DNA copy number and the risk of autoimmune diseases: A Mendelian randomization study with meta-analysis

BackgroundMitochondrial DNA plays a crucial role in the pathophysiology of autoimmune diseases (ADs). However, the association between mitochondrial DNA copy number (mtDNA-CN) and ADs risk is controversial. In this study, Mendelian randomization (MR) analysis and meta-analysis were performed using three sets of independent instrumental variables (IVs) to investigate the potential association between mtDNA-CN and 20 types of ADs. MethodsThe three sets of IVs were drawn primarily from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium using different methods. Outcome data for ADs were investigated using summary statistics from the FinnGen cohort. The potential causal associations were assessed using inverse-variance weighting (IVW), MR-Egger, and weighted median methods. Sensitivity analysis and the Steiger test were used to verify the robustness of the MR estimates. In addition, a meta-analysis was conducted to pool the results from three IV groups. ResultsOverall, genetically predicted mtDNA-CN was not associated with ADs risk (OR = 1.046, 95 % CI: 0.964–1.135, P = 0.283). However, subgroup analyses showed positive causal associations of mtDNA-CN with autoimmune hypothyroidism (OR = 1.133, 95 % CI: 1.016–1.262, P = 0.024) and rheumatoid arthritis (OR = 1.219, 95 % CI: 1.028–1.445, P = 0.023). In contrast, there was no causal association between mtDNA-CN and atopic dermatitis as well as psoriasis, ulcerative colitis, adult-onset Still disease, type1 diabetes, Crohn disease, sarcoidosis, ankylosing spondylitis, multiple sclerosis, autoimmune hyperthyroidism, primary sclerosing cholangitis, systemic lupus erythematosus, systemic sclerosis, alopecia areata, myasthenia gravis, Guillain-Barre syndrome, dermatopolymyositis, and vitiligo. ConclusionsThis MR analysis showed mtDNA-CN is causally associated with an increased risk of autoimmune hypothyroidism and rheumatoid arthritis at the genetic level. The findings have important implications for the use of mtDNA-CN as a biomarker for risk assessment of autoimmune hypothyroidism and rheumatoid arthritis in clinical practice.

Application of Multiplex Immunoassay in Aging Research: A Methodological Approach.

One of the characteristics of aging and age-related disorders is the formation and evolution of a chronic, low-grade, and hence subclinical, inflammatory state known as inflammaging. Although the progression of inflammaging is now recognized as one of the main driving forces of aging and one of the main risk factors for morbidity and mortality in older subjects, current knowledge on the causative agents of inflammaging itself and chronic, aging-related diseases is still incomplete. In this chapter, we offer a methodological approach for assessing inflammation associated with aging through the use of multiplex immunoassay, which enables the rapid, reproducible, and simultaneous dosage of several cytokines, chemokines, and inflammatory mediators with little biological sample usage.

The connection between aging, cellular senescence and gut microbiome alterations: A comprehensive review.

The intricate interplay between cellular senescence and alterations in the gut microbiome emerges as a pivotal axis in the aging process, increasingly recognized for its contribution to systemic inflammation, physiological decline, and predisposition to age-associated diseases. Cellular senescence, characterized by a cessation of cell division in response to various stressors, induces morphological and functional changes within tissues. The complexity and heterogeneity of senescent cells, alongside the secretion of senescence-associated secretory phenotype, exacerbate the aging process through pro-inflammatory pathways and influence the microenvironment and immune system. Concurrently, aging-associated changes in gut microbiome diversity and composition contribute to dysbiosis, further exacerbating systemic inflammation and undermining the integrity of various bodily functions. This review encapsulates the burgeoning research on the reciprocal relationship between cellular senescence and gut dysbiosis, highlighting their collective impact on age-related musculoskeletal diseases, including osteoporosis, sarcopenia, and osteoarthritis. It also explores the potential of modulating the gut microbiome and targeting cellular senescence as innovative strategies for healthy aging and mitigating the progression of aging-related conditions. By exploring targeted interventions, including the development of senotherapeutic drugs and probiotic therapies, this review aims to shed light on novel therapeutic avenues. These strategies leverage the connection between cellular senescence and gut microbiome alterations to advance aging research and development of interventions aimed at extending health span and improving the quality of life in the older population.

Establishment of an induced pluripotent cell line (ABCRIi001-A) from an elderly female for ageing research

Human induced pluripotent stem cells (hiPSCs) hold promises to model and understand human diseases, including those associated with ageing. Here, we describe ABCRIi001-A, a hiPSC line generated from peripheral blood mononuclear cells (PBMCs) of a 79-year-old female enrolled in a study for development of an ageing score (ALFA Score). PBMCs were reprogrammed using three Sendai virus-based reprogramming vectors (hKOS, hc-Myc, and hKlf4). ABCRIi001-A showed normal morphology and karyotype, viral clearance, absence of genomic aberrations, and their pluripotency was confirmed by expression of pluripotency-related markers and their ability to differentiate into the three germ layers. ABCRIi001-A is valuable for ageing-related studies.

Characterization of microcirculatory endothelial functions in a D-Galactose-induced aging model

BackgroundMicrocirculation health is critical to human health, and aging is an important factor affecting microcirculation health. Although D-Galactose has been widely used in aging research models, there is a lack of relevant studies on D-Galactose simulating microcirculatory aging. Here, we explored microcirculatory endothelial function in D-Galactose-induced aging mice. MethodsIntraperitoneal injection of 150 mg/(kg·d) of D-Galactose was given to cause senescence in mice. Aging was evaluated by SA-β-gal (senescence-associated β-galactosidase) staining. The auricular skin and hepatic microcirculation of mice were observed and detected by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) and microcirculation apparatus. The aging of microcirculation was analyzed from oxidative stress, endothelial impairment, inflammation, microvascular morphology and hemodynamics. ResultsIn aging mice, percentage of SA-β-gal positive area, oxidative stress products reactive oxygen species (ROS) and nitric oxide (NO), endothelial impairment marker syndecan-1 (SDC-1), stromal cell derived factor-1 (SDF-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the senescence-associated secretory phenotype (SASP) were all up-regulated. The tortuosity of microvessels increased in aging mice, the linear density did not change significantly, but the total length of narrow microvessels (TLNMV) increased and wide microvessels (TLWMV) decreased, speculate that vasomotor dysfunction may be present. Hemodynamically, both perfusion and velocity of blood flow were reduced in senescent mice, presumably due to endothelial dysfunction. ConclusionMicrocirculatory endothelial dysfunction is induced by D-Galactose, leading to microcirculatory aging. In vivo, this is manifested by elevated levels of oxidative stress, impaired endothelial glycocalyx (eGC), and a greater production of chemokines and adhesive molecules. These changes cause vasomotor dysfunction and remodeling, ultimately leading to hemodynamic impairment.

THE DEVELOPMENT OF GERIATRIC AND ANTI-AGING SCIENTIFIC SCHOOL IN UKRAINE

This manuscript explores the historical development and significance of geriatric and anti-aging research in Ukraine, emphasizing its vital role in advancing global gerontology and geriatrics.The manuscript highlights the multidisciplinary aims of Ukrainian gerontological research, including understanding the biological mechanisms of aging, developing medical treatments for chronic diseases prevalent in older populations, and addressing the social and psychological aspects of aging. It also discusses the challenges of Ukraine’s aging population, such as healthcare policy reform, improved geriatric care integration, and increased funding for aging research. A significant emphasis is placed on incorporating anti-aging studies into medical education. By updating medical curricula to include comprehensive anti-aging education, Ukraine can better prepare future healthcare professionals to meet the evolving needs of its aging population. The manuscript concludes that such educational reforms are crucial for enhancing the effectiveness and sustainability of Ukraine’s healthcare system, ultimately improving the quality of life for older adults and aligning with global trends in aging research.

Researchers in low‐ and middle‐income countries for aging and Alzheimer's research (NIA)

Researchers in low‐ and middle‐income countries for aging and Alzheimer's research (NIA)

Caenorhabditis elegans as a Model to Study Aging and Photoaging.

Caenorhabditis elegans (C. elegans) has emerged as an outstanding model organism for investigating the aging process due to its shortened lifespan, well-defined genome, and accessibility of potent genetic tools. This review presents the current findings on chronological aging and photoaging in C. elegans, exploring the elaborate molecular pathways that control these processes. The progression of chronological aging is characterized by a gradual deterioration of physiological functions and is influenced by an interaction of genetic and environmental factors, including the insulin/insulin-like signaling (IIS) pathway. In contrast, photoaging is characterized by increased oxidative stress, DNA damage, and activation of stress response pathways induced by UV exposure. Although the genetic mechanisms of chronological aging in C. elegans have been characterized by extensive research, the pathways regulating photoaging are comparatively less well-studied. Here, we provide an overview of the current understanding of aging research, including the crucial genes and genetic pathways involved in the aging and photoaging processes of C. elegans. Understanding the complex interactions between these factors will provide invaluable insights into the molecular mechanisms underlying chronological aging and photoaging and may lead to novel therapeutic approaches and further studies for promoting healthy aging in humans.

Mapping the research trends and hotspots in vascular aging from 2003–2023: A bibliometric analysis

From the molecular to the cellular to the tissue level, vascular aging is regulated by a complex network involving numerous mechanisms and diseases, and our knowledge of any one level is incomplete and biased. To date, due to the diversity and complexity of the influencing factors, no international standard has been established. Therefore, in this study, we aimed to analyze the global research trends and potential hotspots related to vascular aging. We extracted the relevant publications between January 2003 and December 2023 from the Web of Science Core Collection. VOSviewer and CiteSpace software were used to quantitatively and qualitatively analyze the authors, countries, institutions, and journals in the field of vascular aging. The total number of publications on vascular aging between January 2003 and December 2023 was 1044, showing a steady increase. The United States and the University of Oklahoma published the highest number of research papers in the field. Ungvari Zoltan from the University of Oklahoma was the most productive author (47 papers) on vascular aging, specializing in endothelial cell failure, microcirculation, and aging. Burst detection of keywords revealed that endothelial dysfunction and vascular smooth muscle cells had the highest burst strength, suggesting that these are the current research hot spots in vascular aging research. In conclusion, senescence-associated secretory phenotype, reactive oxygen species, genetic instability, and an imbalance of protein homeostasis, trigger an inflammatory response that affects vascular endothelial and smooth muscle cell function, ultimately leading to vascular aging. This research provides insights into recent advances and preventive strategies in the field of vascular aging.

Immunocompetent Brain Organoids with Microglia Allow Advanced Aging Research.

Aging is a complex and multifactorial process that significantly affects brain function and health, since it is commonly associated with the emergence of neurodegenerative diseases. Recent advances in stem cell technology have facilitated the development of brain organoids, three-dimensional structures that mimic key aspects of brain architecture and functionality. By incorporating microglia, the resident monocyte-derived immune cells of the central nervous system, immunocompetent brain organoids can provide a more physiologically relevant model for studying brain aging. This chapter explores the methodology of immunocompetent brain organoids for advanced aging research, detailing protocols for their generation from a co-culture of neural stem cells and primitive macrophage progenitors.

The Oldest of Old Male C57B/6J Mice Are Protected from Sarcopenic Obesity: The Possible Role of Skeletal Muscle Protein Kinase B Expression

The impact of aging on body composition and glucose metabolism is not well established in C57BL/6J mice, despite being a common pre-clinical model for aging and metabolic research. The purpose of this study was to examine the effect of advancing age on body composition, in vivo glucose metabolism, and skeletal muscle AKT expression in young (Y: 4 months old, n = 7), old (O: 17–18 months old, n = 10), and very old (VO: 26–27 month old, n = 9) male C57BL/6J mice. Body composition analysis, assessed by nuclear magnetic resonance, demonstrated O mice had a significantly greater fat mass and body fat percentage when compared to Y and VO mice. Furthermore, VO mice had a significantly greater lean body mass than both O and Y mice. We also found that the VO mice had greater AKT protein levels in skeletal muscle compared to O mice, an observation that explains a portion of the increased lean body mass in VO mice. During glucose tolerance (GT) testing, blood glucose values were significantly lower in the VO mice when compared to the Y and O mice. No age-related differences were observed in insulin tolerance (IT). We also assessed the glucose response to AMPK activation by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). The change in blood glucose following AICAR administration was significantly reduced in VO mice compared to Y and AG mice. Our findings indicate that lean body mass and AKT2 protein expression in muscle are significantly increased in VO mice compared to O mice. The increase in AKT2 likely plays a role in the greater lean body mass observed in the oldest of old mice. Finally, despite the increased GT, VO mice appear to be resistant to AMPK-mediated glucose uptake.