Physiological Decline Research Articles

Leading limb biomechanical response following compelled forward and descending body shift in old versus young adults

BackgroundFalls pose a significant health risk in older adults, with stair descent falls carrying particularly severe consequences. Reduced balance control and limb support due to aging-related physiological and neuromuscular decline are critical components in increased falling risk in older adults. Understanding the age-associated abnormalities in balance control and limb support strategies during sudden forward and downward body shift could reveal potential biomechanical deficits responsible for increased falling risks in older adults.This study investigates balance regulatory responses following first-time exposure to compelled forward and downward body shift in young and older adults. MethodsThirteen healthy old and thirteen healthy young adults participated in this study. Participants stood on two adjacent perturbation platforms in modified tandem stance. The leading limb support surface dropped 3 in. vertically at an unknown time. The anterior margin of stability and center of mass velocity, peak vertical ground reaction forces, and leading limb ankle and knee joint angular displacement, torque, and power during the initial response phase were compared between age groups. FindingsCompared to young adults, older adults showed higher center of mass velocity, lower margin of stability, peak vertical ground reaction force, peak ankle and knee joint power, and peak knee joint torque during the initial response phase. InterpretationsThe abnormalities potentially identified in our study, particularly in dynamic stability regulation, limb support force generation, and shock absorption may affect the ability to arrest the body's forward and downward motion. These deficits may contribute to an increased risk of forward falls in aging.

The Role of Telomere Length in Stress-related Aging and its Implications for Mental Health

Telomeres, the protective caps at chromosome ends, have emerged as crucial biomarkers of cellular aging and potential mediators of stress-induced physiological decline. This review synthesized current evidence on how chronic stress and various mental health conditions are associated with accelerated telomere shortening, potentially serving as a biological mechanism linking psychological distress to cellular aging and increased risk of age-related diseases. Research studies showed that major depressive disorder, post-traumatic stress disorder, and anxiety disorders have been consistently linked to shorter telomeres, while findings for bipolar disorder and schizophrenia remain mixed. The review explored the biological mechanisms underlying stress-induced telomere attrition, including oxidative stress, inflammation, and dysregulation of the hypothalamic-pituitary-adrenal axis. It critically evaluated telomere length as a potential biomarker for stress-related aging and mental health disorders, assessing its reliability and clinical relevance. The review also examined interventions targeting telomere biology, including lifestyle modifications, stress reduction techniques, and pharmacological approaches. These interventions showed promise in mitigating the effects of stress-related aging and improving mental health outcomes. However, methodological challenges and high inter-individual variability currently limit the clinical utility of telomere length assessment. Ethical implications of telomere-based interventions and diagnostics were also discussed, including issues of privacy, potential discrimination, and the blurring lines between treatment and enhancement.

The SLC38A9–mTOR axis is involved in autophagy in the juvenile yellow catfish (Pelteobagrus fulvidraco) under ammonia stress

The primary objective of this study was to examine the effect of acute ammonia stress on hepatic physiological alterations in yellow catfish by performing a comprehensive analysis of the metabolome and transcriptome. The present study showed that ammonia stress led to liver metabolic disruption, functional incapacitation, and oxidative damage. Transcriptomic and metabolomic analyses revealed transcriptional and metabolic differences in the liver of yellow catfish under control and high ammonia stress conditions. After 96 h of acute exposure to ammonia, the mRNA levels of 596 liver genes were upregulated, whereas those of 603 genes were downregulated. Enrichment analysis of the differentially expressed genes identified multiple signalling pathways associated with autophagy, including the endocytosis, autophagy-animal, and mammalian target of rapamycin signalling pathways. A total of 186 upregulated and 117 downregulated metabolites, primarily associated with amino acid biosynthesis pathways, were identified. Multi-omics integration revealed the solute carrier family 38 member 9 (SLC38A9)-mammalian target of rapamycin axis as a signalling nexus for amino acid-mediated modulation of autophagy flux, and q-PCR was used to assess the expression of autophagy-related genes (LC3a and sqstm1), revealing an initial inhibition followed by the restoration of autophagic flux during ammonia stress. Subsequent utilisation of arginine as a specific SLC38A9 activator during ammonia stress demonstrated that augmented SLC38A9 expression hindered autophagy, exacerbated ammonia toxicity, and caused a physiological decline (total cholesterol, total triglyceride, acid phosphatase, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels were significantly increased), oxidative stress, and apoptosis. Autophagy activation may be an adaptive mechanism to resist ammonia stress.

THE INTERTISSUE COMMUNICATION BETWEEN THE HYPOTHALAMUS AND WHITE ADIPOSE TISSUE IN MAMMALIAN AGING AND LONGEVITY CONTROL

Abstract Recent studies in model organisms have demonstrated that the intertissue communications play a critical role in the regulation of aging and longevity. Our major goal is to understand the systemic regulation of aging and longevity in mammals and translate that knowledge into an effective anti-aging intervention that could make our later lives as healthy and productive as possible (“productive aging”). In mammals, we have previously demonstrated that the intertissue communication between the hypothalamus and adipose tissue, particularly mediated by extracellular vesicles-contained extracellular nicotinamide phosphoribosyltrasferase (eNAMPT), the rate-limiting NAD+ biosynthetic enzyme in mammals, functions to counteract age-associated physiological decline and promote longevity in mice. We have recently found that Ppp1r17-positive neurons in the dorsomedial hypothalamus (DMHPpp1r17 neurons) regulate white adipose tissue (WAT) function, including lipolysis and eNAMPT secretion, through the sympathetic nervous system (SNS), and the feedback loop between DMHPpp1r17 neurons and WAT plays a critical role in the regulation of aging and longevity in mice. Within DMHPpp1r17 neurons, the phosphorylation and subsequent nuclear-cytoplasmic translocation of Ppp1r17, regulated by cGMP-dependent protein kinase (PKG; Prkg1), affect gene expression regulating synaptic function, causing synaptic transmission dysfunction and impaired WAT function. Both DMH-specific Prkg1-knockdown, which suppresses age-associated Ppp1r17 translocation, and the chemogenetic activation of DMHPpp1r17 neurons significantly ameliorate age-associated WAT dysfunction, increase physical activity, decrease age-associated mortality rate, and extend lifespan. Thus, these findings clearly demonstrate the importance of the intertissue communication between the hypothalamus and WAT in mammalian aging and longevity control and provide critical insights into the development of effective anti-aging interventions.

BIOMARKERS HELP CLARIFY HOW SYSTEMIC AGING CONTRIBUTES TO MORTALITY: UTILIZING A MACHINE-LEARNING APPROACH IN HRS

Abstract Research suggests aging is a coordinated physiological decline occurring in multiple systems and at multiple biological levels. However, it is largely unknown how general biological aging and specific systemic aging co-occur and influence one another to affect mortality. There is also emerging interest in understanding how social exposures may differentially accelerate decline in individual physiological systems. We utilize data from the Health and Retirement Study, a nationally representative sample of about 4000 US adults over age 55. We used eXtreme Gradient Boosting (xgboost) in a training subsample to create estimates of mortality risk based on sets of biomarkers representing biological systems (e.g., brain and nervous system, adaptive immune system, cardiovascular system, renal system) as well as cellular aging (using epigenetic clocks and telomere length). These models generated mortality risk scores for each system (e.g., renal functioning using BUN, creatinine, and cystatin C). Mortality was regressed on these scores in a testing subsample to assess the relative impact of each system on mortality risk. Results suggest cellular aging, cardiovascular aging, and age-related metabolic dysfunction contribute most to mortality risk. Aging of these systems also partially mediates the mortality risk associated with age, race/ethnicity, sex, and education. These results suggest aging of specific systems may be differentially affected by sociodemographic exposures and may differentially contribute to mortality risk. This research may help guide interventions focused on reducing inequalities in mortality risk by identifying health risks that would have the greatest impact on mortality at the population level.

Association between Grip Strength and Future Cognitive Function in male

AbstractBackgroundFrailty is an aging‐related syndrome of physiological decline, and has been associated with cognitive function.Grip strength, could be used as a marker for frailty and older adult health status. Frailty has been associated with cognitive function. However, its mechanism has not been fully investigated.We aimed to investigate the association between grip strength with cognitive function.MethodWe prospectively recruited 184 participants who underwent a grip strength test, cognitive function test. Data was collected from the Korean Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), an ongoing prospective cohort study which started in 2014. Frailty was represented by grip strength (kg). Cognitive function was assessed using Mini‐Mental State Examination(MMSE) and The Consortium to Establish a Registry for Alzheimer’s Disease‐K(CERAD‐K).Multiple linear regression models were used to analyze the associations between grip strength and cognitive function. We adjusted age, gender, years of education, and BMI.ResultAmong 184 participants, 119 (64.7%) were cognitively normal. 32 (17.4%) were diagnosed with mild cognitive impairment and 33 (17.9) were a probable AD. Mean age of the participants was 69.4 (8.2) years. 43.5% of the participants were female. Grip strength was positively associated with MMSE at 1 year later in male (ß = 0.182 p = 0.004). In terms of cognitive domain, verbal and visual memory, language, visuospatial, and frontal‐executive functions were related to grip strength (vebal memory: ß = 0.037 p = 0.022, visual memory: ß = 0.046 p = 0.002, language: ß = 0.055 p<0.001, visuospatial: ß = 0.068 p = 0.0213, frontal‐executive: ß = 0.050 p<0.001).ConclusionWeakness of grip strength is associated with decreased future cognitive function. This support concept that grip strength could be a marker for cognitive decline.

Frailty in Geriatric Patients with Head and Neck Cancer and its Implication in Survivorship

The aging population, particularly those aged 65 and above, is on the rise, with projections indicating a substantial increase in the elderly demographic. This demographic shift brings challenges in managing age-related diseases, including head and neck cancers (HNCs). Frailty, often characterized by physiological decline and vulnerability to stressors, is a crucial factor affecting treatment outcomes of elderly cancer patients. Accordingly, the significance of assessing frailty in elderly HNC patients before their treatment should be emphasized, but current frailty assessment tools may not fully capture the unique challenges faced by HNC patients. Specific indicators, including respiratory and swallowing functions, are proposed for a more tailored assessment. This comprehensive review explores the impact of frailty on various treatment modalities, including surgery, radiation, and chemotherapy, highlighting the need for personalized interventions. Furthermore, it suggests avenues for future research to enhance frailty assessment tools and investigate interventions aimed at improving treatment outcomes in elderly HNC patients.

Could the Combination of eGFR and mGPS Facilitate the Differential Diagnosis of Age-Related Renal Decline from Diseases? A Large Study on the Population of Western Sicily

The assessment of renal function is critical to diagnosing and managing renal age-related decline, disease (KD), and failure, which are prevalent in the elderly population. The glomerular filtration rate (GFR) is widely used as an indicator of kidney function, but its direct measurement is challenging, as are its age and gender caveats. This makes difficult the differential diagnosis between age-related physiological decline and KD and/or failure. Currently, the inflammation-based modified Glasgow prognostic score (mGPS) is emerging as a promising biomarker of several inflammatory acute/chronic diseases. In this study, the large variability of eGFR with age and gender was evaluated as the association of eGFR values with mGPS levels. A population of 57,449 adult participants (age ≥ 18 years) was enrolled. Appropriate circulating biomarkers were measured to detect eGFR and mGPS values. The data obtained demonstrated a significant decrease in eGFR in men vs. women across the four selected age classes (18–40, 40–60, 60–80, 80–100 years); eGFR classes were significantly associated with mGPS (p < 0.001), as were age classes and gender with mGPS categories. Accordingly, the percentage of people having an mGPS score = 2 significantly increased across the eGFR classes: with an 11% in the G1/eGFR class needed to achieve 44% in G5/eGFR. Thus, the combination of mGPS with eGFR could represent the best benchmark risk model for the differential diagnosis of kidney disease from the age-related eGFR reduction.

Medicinal foods and plants with antiaging properties: A review of in vitro and in vivo studies

AbstractAging is a natural process by which organisms experience physiological decline leading to susceptibility to morbidity and mortality. There are no known antiaging drugs but there is a myriad of medicinal foods and plants that have been used in managing the state. Several studies have also been conducted on the antiaging properties of medicinal plants and foods, but these pieces of information are scattered. This paper attempts to integrate available information on medicinal foods and plants as well as isolated chemical compounds with antiaging potential. It also provides different models (in vitro and in vivo) that are used in evaluating the potency of natural products. Current literature on the subject was obtained from different databases such as PubMed, Google Scholar, and Web of Science. A total of 119 medicinal plants and 50 isolated compounds were reported in this study. Different models were also used to evaluate the efficacy of these plants which include in vitro (enzyme inhibition, use of cell lines) and in vivo (Caenorhabditis elegans, yeast, fruit fly, mice, and rats) models. It can be concluded that medicinal foods and plants are reservoirs of potential therapeutic agents that can efficiently modulate metabolic processes implicated in aging and its associated disorders.

Temporal Dynamics of Epigenetic Aging and Frailty From Midlife to Old Age.

DNA methylation-derived epigenetic clocks and frailty are well-established biological age measures capturing different aging processes. However, whether they are dynamically linked to each other across chronological age remains poorly understood. This analysis included 1 309 repeated measurements in 524 individuals aged 50-90 years from the Swedish Adoption/Twin Study of Aging. Frailty was measured using a validated 42-item frailty index (FI). Five epigenetic clocks were calculated, including 4 principal component (PC)-based clocks trained on chronological age (PCHorvathAge and PCHannumAge) and aging-related physiological conditions (PCPhenoAge and PCGrimAge), and a pace of aging clock (DunedinPACE). Using dual change score models, we examined the dynamic, bidirectional associations between each of the epigenetic clocks and the FI over age to test for potential causal associations. The FI exhibited a nonlinear, accelerated increase across the older adulthood, whereas the epigenetic clocks mostly increased linearly with age. For PCHorvathAge, PCHannumAge, PCPhenoAge, and PCGrimAge, their associations with the FI were primarily due to correlated levels at age 50 but with no evidence of a dynamic longitudinal association. In contrast, we observed a unidirectional association between DunedinPACE and the FI, where a higher DunedinPACE predicted a subsequent increase in the FI, but not vice versa. Our results highlight a temporal order between epigenetic aging and frailty such that changes in DunedinPACE precede changes in the FI. This potentially suggests that the pace of aging clock can be used as an early marker of the overall physiological decline at system level.

Voluntary private health insurance and management of frailty in European Health Systems: a longitudinal analysis

Abstract Frailty is a major health concern associated with aging. It is a state of multisystem physiological decline and inability to maintain homeostasis, gradually leading to an increased risk of multiple adverse outcomes, such as falls, hospitalizations, and death. The prevalence of frailty in community-dwelling older Europeans (65 years and older) varies between 5.8% and 27.3%; in addition, between 34.6% and 50.9% are classified as ‘pre-frail’. In the face of the rapid population ageing occurring in Western societies, frailty is set to reach epidemic proportions over the next few decades. Although most European health care system offer essential treatment free of charge, voluntary private health insurances (VPHI) are becoming more common. Their coverage can be complementary or supplementary including access, faster treatment, waiting list avoidance, and out-of-pocket refund. A growing body of evidence is showing that there is erosion of the universal health coverage in European Health Systems and accessing VPHI might impact quality of care, especially for complex conditions i.e. Frailty. Using European data from the 2013 to 2011 we will assess trends of VPHI in individuals 65 years and older and whether accessing VPHI impacts frailty management and quality of life for elderly Europeans who are frail. These findings will help assessing quality of frailty management in European Health Systems and identify possible inequalities in accessing health services.

β-nicotinamide mononucleotide rescues the quality of aged oocyte and improves subsequent embryo development in pigs.

Oocyte senescence alters the shape and function, thereby weakening the fertilization potential. Nicotinamide mononucleotide (NMN) reverses age-related dysfunctions in various organs. Studies had shown long-term administration of NMN reduced the physiological decline associated in aged mice and reversed the aging of the ovaries. However, the protective effect of NMN on aged porcine oocytes is still unclear. In this study, we investigated the effects of NMN on aging porcine oocytes and subsequent embryonic development. We established a model of senescence of porcine oocytes after ovulation by extending the culture time in vitro. NMN supplementation significantly reduced reactive oxygen species (ROS) levels in senescence oocytes and increased the mRNA levels of antioxidant genes SOD1 and Cat. The mitochondrial membrane potential of aged oocytes treated with NMN was increased compared with that of untreated oocytes. In addition, the mRNA level of apoptosis-related gene Bax was significantly decreased in senescence oocytes treated with NMN, while the mRNA level of anti-apoptosis-related gene BCL-2 was significantly increased. Furthermore, NMN supplementation enhanced the subsequent development ability of senescent oocytes during in vitro aging. Compared with untreated senescent oocytes, the blastocyst formation rate and pluripotent genes of senescent oocytes treated with NMN were significantly increased. Taken together, these results suggest that NMN is beneficial for delaying the aging process in porcine oocytes.

Application of MFI-5 in severe complications and unfavorable outcomes after radical resection of colorectal cancer

BackgroundFrailty is considered a characteristic manifestation of physiological decline in multiple organ systems, which significantly increases the vulnerability of elderly individuals with colorectal cancer (CRC) and is associated with a poor prognosis. While studies have demonstrated that the 11-factor Modified Frailty Index (mFI-11) can effectively predict adverse outcomes following radical resection of CRC, there is a lack of research on the applicability of the 5-factor Modified Frailty Index (mFI-5) within this patient population.MethodsIn this retrospective analysis, we examined a cohort of CRC patients aged 65 years and above who had undergone radical resection. For each patient, we calculated their mFI-5 score, considering a score of ≥ 2 as an indication of frailty. We conducted univariate and multivariate analyses to assess the association between the mFI-5 and adverse outcomes as well as postoperative complications.ResultsPatients with an mFI-5 score ≥ 2 exhibited a significantly higher incidence of serious postoperative complications (53% vs. 30%; P = 0.001) and experienced a longer hospital stay [19.00 (15.00–24.50) vs. 17.00 (14.00–20.00); P < 0.05]. Notably, an mFI-5 score greater than 2 emerged as an independent risk factor for severe postoperative complications (odds ratio: 2.297; 95% confidence interval: 1.216 to 4.339; P = 0.01). Furthermore, the mFI-5 score displayed predictive capabilities for severe postoperative complications with an area under the receiver operating characteristic (ROC) curve of 0.629 (95% confidence interval: 0.551 to 0.707; P < 0.05).ConclusionThe mFI-5 demonstrates a high level of sensitivity in predicting serious complications, prolonged hospital stays, and mortality following radical resection of colorectal carcinoma. As a practical clinical assessment tool, the mFI-5 enables the identification of high-risk patients and facilitates preoperative optimization.

Deep neural network-estimated age using optical coherence tomography predicts mortality

The concept of biological age has emerged as a measurement that reflects physiological and functional decline with ageing. Here we aimed to develop a deep neural network (DNN) model that predicts biological age from optical coherence tomography (OCT). A total of 84,753 high-quality OCT images from 53,159 individuals in the UK Biobank were included, among which 12,631 3D-OCT images from 8,541 participants without any reported medical conditions at baseline were used to develop an age prediction model. For the remaining 44,618 participants, OCT age gap, the difference between the OCT-predicted age and chronological age, was calculated for each participant. Cox regression models assessed the association between OCT age gap and mortality. The DNN model predicted age with a mean absolute error of 3.27 years and showed a strong correlation of 0.85 with chronological age. After a median follow-up of 11.0 years (IQR 10.9–11.1 years), 2,429 deaths (5.44%) were recorded. For each 5-year increase in OCT age gap, there was an 8% increased mortality risk (hazard ratio [HR] = 1.08, CI:1.02–1.13, P = 0.004). Compared with an OCT age gap within ± 4 years, OCT age gap less than minus 4 years was associated with a 16% decreased mortality risk (HR = 0.84, CI: 0.75–0.94, P = 0.002) and OCT age gap more than 4 years showed an 18% increased risk of death incidence (HR = 1.18, CI: 1.02–1.37, P = 0.026). OCT imaging could serve as an ageing biomarker to predict biological age with high accuracy and the OCT age gap, defined as the difference between the OCT-predicted age and chronological age, can be used as a marker of the risk of mortality.

Physiologic changes in the hepatopulmonary syndrome before and after liver transplant: A longitudinal and predictor analysis.

Hepatopulmonary syndrome (HPS) is a common complication of liver disease defined by abnormal oxygenation and intrapulmonary vascular dilatation, treated with liver transplantation. Little is known about changes in HPS physiological parameters over time. We sought to describe baseline clinical and physiological characteristics in HPS and their relationships, temporal changes in physiological parameters before and after transplant, and predictors of changes in oxygenation. This was a retrospective cohort study in the Canadian HPS Program (n = 132). Rates of change after diagnosis were: -3.7 (-6.4, -0.96) mmHg/year for partial pressure of arterial oxygen (PaO 2 ); -26 (-96, 44)m/year for 6-minute walk distance, and 3.3% (-6.6, -0.011) predicted/year for diffusion capacity. Noninvasive shunt of ≥ 20% predicted a slower PaO 2 decline by 0.88 (0.36, 1.4) mmHg/month. We identified 2 PaO 2 deterioration classes-"very severe disease, slow decliners" (PaO 2 45.0mmHg; -1.0mmHg/year); and "moderate disease, steady decliners" (PaO 2 65.5mm Hg; -2.5mmHg/year). PaO 2 increased by 6.5 (5.3, 7.7) mmHg/month in the first year after transplant. The median time to normalization was 149 (116, 184) days. Posttransplant improvement in PaO 2 was 2.5 (0.1, 4.9) mmHg/month faster for every 10mmHg greater pretransplant orthodeoxia. We present a large and long longitudinal data analysis in HPS. In addition to rates of physiological decline and improvement before and after liver transplantation, we present novel predictors of PaO 2 decline and improvement rates. Our findings enhance our understanding of the natural history of HPS and provide pathophysiologic clues. Importantly, they may assist providers in prognostication and prioritization before and after transplant.

Holistic frailty prevention: The promise of movement-based mind-body therapies.

Aging is characterized by fundamental cellular and molecular hallmarks that result in physiologic decline of most body systems. This may culminate in frailty, a state of decreased reserve. Because frailty is a state of multisystem dysregulation, multimodal interventions may be necessary to mitigate and prevent progression rather than interventions targeting a single system. Movement-based mind-body therapies, such as tai chi and yoga, are promising multimodal strategies for frailty prevention and treatment given their inherent multicomponent nature. In this review, we summarize the links between hallmarks of aging and frailty and how tai chi and yoga may impact these hallmarks. We review trial evidence for the impact of tai chi and yoga on frailty in older populations and discuss opportunities for future research.

SIRT7: the seventh key to unlocking the mystery of aging.

Aging is a chronic yet natural physiological decline of the body. Throughout life, humans are continuously exposed to a variety of exogenous and endogenous stresses, which engender various counteractive responses at the cellular, tissue, organ, as well as organismal levels. The compromised cellular and tissue functions that occur because of genetic factors or prolonged stress (or even the stress response) may accelerate aging. Over the last two decades, the sirtuin (SIRT) family of lysine deacylases has emerged as a key regulator of longevity in a variety of organisms. SIRT7, the most recently identified member of the SIRTs, maintains physiological homeostasis and provides protection against aging by functioning as a watchdog of genomic integrity, a dynamic sensor and modulator of stresses. SIRT7 decline disrupts metabolic homeostasis, accelerates aging, and increases the risk of age-related pathologies including cardiovascular and neurodegenerative diseases, pulmonary and renal disorders, inflammatory diseases, and cancer, etc. Here, we present SIRT7 as the seventh key to unlock the mystery of aging, and its specific manipulation holds great potential to ensure healthiness and longevity.

Age-Related Cognitive Decline, Focus on Microbiome: A Systematic Review and Meta-Analysis.

Aging is a complex process influenced by genetics and the environment, leading to physiological decline and increased susceptibility to diseases. Cognitive decline is a prominent feature of aging, with implications for different neurodegenerative disorders. The gut microbiome has gained attention for its potential impact on health and disease, including cognitive function. This systematic review and meta-analysis aimed to investigate the relationship between the gut microbiome and cognitive function in the context of aging. Following PRISMA guidelines, a comprehensive search strategy was employed in PubMed, Scopus, and Web of Science databases. Studies exploring the role of the microbiome in cognition and neurodegenerative disorders, published between 2013 and 2023, were included. Data extraction and quality assessment were performed. Quantitative synthesis using statistical analyses was performed to examine microbial diversity and relative abundance in various cognitive conditions. Sixteen studies involving a total of 1303 participants were included in the analysis. The gut microbiota's relative abundance was different in individuals with cognitive impairments such as Alzheimer's disease, Parkinson's disease, and dementia, compared to the healthy controls. The most prevalent phyla affected were Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Meta-analyses indicated substantial heterogeneity among studies focusing on Alzheimer's disease. The overall quality of evidence related to microbial analysis was moderate. The gut microbiome's role in cognitive decline and neurodegenerative disorders warrants investigation. Altered microbial abundance, particularly in specific phyla, is associated with cognitive impairments. However, variations in study findings and methodologies highlight the complexity of the relationship between the gut microbiome and cognitive function. Further studies are needed to better understand the mechanisms underlying this connection and its potential implications for aging and cognitive health.

Metabolic elasticity: A new measure of age

Promoting healthy aging is contingent on understanding the underlying mechanisms for the age-associated decline in metabolic physiology. Through developing a novel concept of "metabolic elasticity" to evaluate metabolic adaptability in response to cyclical changes in energy balance, Zhou etal. present an impactful gauge of metabolic health that is particularly relevant to aging.

Impact of vessel morphology on CT-derived fractional-flow-reserve in non-obstructive coronary artery disease in right coronary artery

ObjectivesComputed tomography (CT)–derived fractional flow reserve (FFRCT) decreases continuously from proximal to distal segments of the vessel due to the influence of various factors even in non-obstructive coronary artery disease (NOCAD). It is known that FFRCT is dependent on vessel-length, but the relationship with other vessel morphologies remains to be explained.PurposeTo investigate morphological aspects of the vessels that influence FFRCT in NOCAD in the right coronary artery (RCA).MethodsA total of 443 patients who underwent both FFRCT and invasive coronary angiography, with < 50% RCA stenosis, were evaluated. Enrolled RCA vessels were classified into two groups according to distal FFRCT: FFRCT ≤ 0.80 (n = 60) and FFRCT > 0.80 (n = 383). Vessel morphology (vessel length, lumen diameter, lumen volume, and plaque volume) and left-ventricular mass were assessed. The ratio of lumen volume and vessel length was defined as V/L ratio.ResultsWhereas vessel-length was almost the same between FFRCT ≤ 0.80 and > 0.80, lumen volume and V/L ratio were significantly lower in FFRCT ≤ 0.80. Distal FFRCT correlated with plaque-related parameters (low-attenuation plaque, intermediate-attenuation plaque, and calcified plaque) and vessel-related parameters (proximal and distal vessel diameter, vessel length, lumen volume, and V/L ratio). Among all vessel-related parameters, V/L ratio showed the highest correlation with distal FFRCT (r = 0.61, p < 0.0001). Multivariable analysis showed that calcified plaque volume was the strongest predictor of distal FFRCT, followed by V/L ratio (β-coefficient = 0.48, p = 0.03). V/L ratio was the strongest predictor of a distal FFRCT ≤ 0.80 (cut-off 8.1 mm3/mm, AUC 0.88, sensitivity 90.0%, specificity 76.7%, 95% CI 0.84–0.93, p < 0.0001).ConclusionsOur study suggests that V/L ratio can be a measure to predict subclinical coronary perfusion disturbance.Clinical relevance statementA novel marker of the ratio of lumen volume to vessel length (V/L ratio) is the strongest predictor of a distal CT-derived fractional flow reserve (FFRCT) and may have the potential to improve the diagnostic accuracy of FFRCT.Key Points• Physiological FFRCT decline depends not only on vessel length but also on the lumen volume in non-obstructive coronary artery disease in the right coronary artery.• FFRCT correlates with plaque-related parameters (low-attenuation plaque, intermediate-attenuation plaque, and calcified plaque) and vessel-related parameters (proximal and distal vessel diameter, vessel length, lumen volume, and V/L ratio).• Of vessel-related parameters, V/L ratio is the strongest predictor of a distal FFRCT and an optimal cut-off value of 8.1 mm3/mm.