Editorial for the special issue on "microbiomes in extremes of aging".

This special issue of the Journal of Experimental Gerontology explores the dynamic interplay between microbiomes and aging-related conditions. The four selected studies highlight the role of microbiota in Alzheimer's disease, cancer immunotherapy, myocardial infarction and tryptophan metabolism, providing insights into how microbiomes influence health and disease in aging. These studies underscore the potential for microbiome-targeted interventions to mitigate aging-related disorders and improve the quality of life for older adults.

Abnormalities in gut virome signatures linked with cognitive impairment in older adults.

Multiple emerging lines of evidence indicate that the microbiome contributes to aging and cognitive health. However, the roles of distinct microbial components, such as viruses (virome) and their interactions with bacteria (bacteriome), as well as their metabolic pathways (metabolome) in relation to aging and cognitive function, remain poorly understood. Here, we present proof-of-concept results from a pilot study using datasets ( = 176) from the Microbiome in Aging Gut and Brain (MiaGB) consortium, demonstrating that the human virome signature significantly differs across the aging continuum (60s vs.

Targeted and untargeted lipidomics with integration of liver dynamics and microbiome after dietary reversal of obesogenic diet targeting inflammation-resolution signaling in aging mice.

Obesity, a global epidemic linked to around 4 million deaths yearly, arises from lifestyle imbalances impacting inflammation-related conditions like non-alcoholic fatty liver disease and gut dysbiosis. But the long-term effects of inflammation caused by lifestyle-related dietary changes remain unexplained. In this study, we used young male C57Bl/6 mice which were fed either an obesogenic diet (OBD) or a control diet (CON) for six months.

From Gut Microbiota to Brain Waves: The Potential of the Microbiome and EEG as Biomarkers for Cognitive Impairment.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder and a leading cause of dementia. Aging is a significant risk factor for AD, emphasizing the importance of early detection since symptoms cannot be reversed once the advanced stage is reached. Currently, there is no established method for early AD diagnosis.

Dynamics of serum exosome microRNA profile altered by chemically induced estropause and rescued by estrogen therapy in female mice.

The decline in the ovarian reserve leads to menopause and reduced serum estrogens. MicroRNAs are small non-coding RNAs, which can regulate gene expression and be secreted by cells and trafficked in serum via exosomes. Serum miRNAs regulate tissue function and disease development.

Association of Common Foods with Inflammation and Mortality: Analysis from a Large Prospective Cohort Study.

Some dietary patterns are associated with inflammation, while others lower inflammation and improve health. However, many people cannot follow a complete, healthy diet. Therefore, this study's aim was to identify specific foods associated chronic inflammation and mortality.

Oro-Respiratory Dysbiosis and Its Modulatory Effect on Lung Mucosal Toxicity during Exposure or Co-Exposure to Carbon Nanotubes and Cigarette Smoke.

The oro-respiratory microbiome is impacted by inhalable exposures such as smoking and has been associated with respiratory health conditions. However, the effect of emerging toxicants, particularly engineered nanoparticles, alone or in co-exposure with smoking, is poorly understood. Here, we investigated the impact of sub-chronic exposure to carbon nanotube (CNT) particles, cigarette smoke extract (CSE), and their combination.

Abnormalities in microbiota/butyrate/FFAR3 signaling in aging gut impair brain function.

Aging-related abnormalities in gut microbiota are associated with cognitive decline, depression, and anxiety, but underlying mechanisms remain unstudied. Here, our study demonstrated that transplanting old gut microbiota to young mice induced inflammation in the gut and brain coupled with cognitive decline, depression, and anxiety. We observed diminished mucin formation and increased gut permeability ("leaky gut") with a reduction in beneficial metabolites like butyrate because of decline in butyrate-producing bacteria in the aged gut microbiota.

New horizon to the world of gut microbiome: seeds germination.

The second brain of humans has been known as the microbiome. The microbiome is a dynamic network composed of commensal bacteria, archaea, viruses, and fungi colonized in the human gastrointestinal tract. They play a vital role in human health by metabolizing components, maturation of the immune system, and taking part in the treatment of various diseases.

Fisetin modulates the gut microbiota alongside biomarkers of senescence and inflammation in a DSS-induced murine model of colitis.

Colitis, a subtype of inflammatory bowel disease (IBD), is a multifactorial disorder characterized by chronic inflammation of the colon. Among various experimental models used in the study of IBD, the chemical colitogenic dextran sulfate sodium (DSS) is most commonly employed to induce colitis in vivo. In the search for new therapeutic strategies, Fisetin, a flavonoid found in many fruits and vegetables, has recently garnered attention for its senolytic properties.

Intestinal FFA2 promotes obesity by altering food intake in Western diet-fed mice.

Short-chain fatty acids (SCFAs) are key nutrients that play a diverse set of roles in physiological function, including regulating metabolic homeostasis. Generated through the fermentation of dietary fibers in the distal colon by the gut microbiome, SCFAs and their effects are partially mediated by their cognate receptors, including free fatty acid receptor 2 (FFA2). FFA2 is highly expressed in the intestinal epithelial cells, where its putative functions are controversial, with numerous in vivo studies relying on global knockout mouse models to characterize intestine-specific roles of the receptor.

Poor Oral Health Linked with Higher Risk of Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease characterized by cognitive and behavioral changes in older adults. Emerging evidence suggests poor oral health is associated with AD, but there is a lack of large-scale clinical studies demonstrating this link. Herein, we used the TriNetX database to generate clinical cohorts and assess the risk of AD and survival among >30 million de-identified subjects with normal oral health ( = 31,418,814) and poor oral health ( = 1,232,751).

The Triple Alliance: Microbiome, Mitochondria, and Metabolites in the Context of Age-Related Cognitive Decline and Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive, age-related neurodegenerative disorder that affects a large proportion of the older population. It currently lacks effective treatments, placing a heavy burden on patients, families, health care systems, and society. This is mainly due to our limited comprehension of the pathophysiology of AD progression, as well as the lack of effective drug targets and intervention timing to address the underlying pathology.

Geroprotective potential of microbiome modulators in the Caenorhabditis elegans model.

Aging is associated with cellular and physiological changes, which significantly reduce the quality of life and increase the risk for disease. Geroprotectors improve lifespan and slow the progression of detrimental aging-related changes such as immune system senescence, mitochondrial dysfunction, and dysregulated nutrient sensing and metabolism. Emerging evidence suggests that gut microbiota dysbiosis is a hallmark of aging-related diseases and microbiome modulators, such as probiotics (live bacteria) or postbiotics (non-viable bacteria/bacterial byproducts) may be promising geroprotectors.

The interactive effects of psychosocial stress and diet composition on health in primates.

Social disadvantage and diet composition independently impact myriad dimensions of health. They are closely entwined, as social disadvantage often yields poor diet quality, and may interact to fuel differential health outcomes. This paper reviews effects of psychosocial stress and diet composition on health in nonhuman primates and their implications for aging and human health.

CDK4-E2F3 signals enhance oxidative skeletal muscle fiber numbers and function to affect myogenesis and metabolism.

Understanding how skeletal muscle fiber proportions are regulated is vital to understanding muscle function. Oxidative and glycolytic skeletal muscle fibers differ in their contractile ability, mitochondrial activity, and metabolic properties. Fiber-type proportions vary in normal physiology and disease states, although the underlying mechanisms are unclear.

Unique trans-kingdom microbiome structural and functional signatures predict cognitive decline in older adults.

The prevalence of age-related cognitive disorders/dementia is increasing, and effective prevention and treatment interventions are lacking due to an incomplete understanding of aging neuropathophysiology. Emerging evidence suggests that abnormalities in gut microbiome are linked with age-related cognitive decline and getting acceptance as one of the pillars of the Geroscience hypothesis. However, the potential clinical importance of gut microbiome abnormalities in predicting the risk of cognitive decline in older adults is unclear.

Emerging pre-clinical safety assessments for potential probiotic strains: a review.

Probiotics are amply studied and applied dietary supplements of greater consumer acceptance. Nevertheless, the emerging evidence on probiotics-mediated potential risks, especially among immunocompromised individuals, necessitates careful and in-depth safety studies. The traditional probiotic safety evaluation methods investigate targeted phenotypic traits, such as virulence factors and antibiotic resistance.

Sleep deprivation in obesogenic setting alters lipidome and microbiome toward suboptimal inflammation in acute heart failure.

Sleep is a fundamental medicine for cardiac homeostasis, and sleep-deprived individuals are prone to higher incidences of heart attack. The lipid-dense diet (obesogenic diet-OBD) is a cumulative risk factor for chronic inflammation in cardiovascular disease; thus, understanding how sleep fragmentation (SF) in an obesity setting impacts immune and cardiac health is an unmet medical need. We hypothesized whether the co-existence of SF with OBD dysregulates gut homeostasis and leukocyte-derived reparative/resolution mediators, thereby impairing cardiac repair.

Intermittent fasting with ketogenic diet: A combination approach for management of chronic diseases.

Intermittent Fasting (IF) is the consumption of food and drinks within a defined time, while the ketogenic diet (KD) switches the metabolism from glucose to fats. Continuation of intermittent fasting leads to the generation of ketones, the exact mechanism for a ketogenic diet. This article discusses the types of IF and KD, the monitoring required, and the mechanisms underlying IF and KD, followed by disorders in which the combination strategy could be applied.

A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut.

Objective: Ample evidence exists for the role of abnormal gut microbiota composition and increased gut permeability ('leaky gut') in chronic inflammation that commonly co-occurs in the gut in both obesity and diabetes, yet the detailed mechanisms involved in this process have remained elusive.

Design: In this study, we substantiate the causal role of the gut microbiota by use of faecal conditioned media along with faecal microbiota transplantation. Using untargeted and comprehensive approaches, we discovered the mechanism by which the obese microbiota instigates gut permeability, inflammation and abnormalities in glucose metabolism.

The effects of prebiotics on gastrointestinal side effects of metformin in youth: A pilot randomized control trial in youth-onset type 2 diabetes.

Disclosure Summary: Dr. Yadav is Chief Scientific Officer and Co-Founder of Postbiotics Inc and has no conflict of interest with this work. All other authors have no conflicts of interest to disclose.