Age-associated Chronic Diseases Research Articles

Impacts of age, type 2 diabetes, and hypertension on circulating neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 after prolonged work in the heat in men.

Prolonged work in the heat increases the risk of acute kidney injury (AKI) in young men. Whether aging and age-associated chronic disease may exacerbate the risk of AKI remains unclear. We evaluated plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum kidney injury molecule-1 (KIM1) before and after 180min of moderate-intensity work (200W/m2) in temperate (wet-bulb globe temperature [WBGT] 16°C) and hot (32°C) environments in healthy young (n = 13, 22years) and older men (n = 12, 59years), and older men with type 2 diabetes (T2D; n = 9, 60years) or hypertension (HTN; n = 9, 60years). There were no changes in NGAL or KIM1 concentrations following prolonged work in temperate conditions in any group. Despite a similar work tolerance, the relative change in NGAL was greater in the older group when compared to the young group following exercise in the hot condition (mean difference + 82ng/mL; p < 0.001). Baseline concentrations of KIM1 were ~ 22pg/mL higher in the older relative to young group, increasing by ~ 10pg/mL in each group after exercise in the heat (both p ≤ 0.03). Despite a reduced work tolerance in the heat in older men with T2D (120 ± 40min) and HTN (108 ± 42min), elevations in NGAL and KIM1 were similar to their healthy counterparts. Age may be associated with greater renal stress following prolonged work in the heat. The similar biomarker responses in T2D and HTN compared to healthy older men, alongside reduced exercise tolerance in the heat, suggest these individuals may exhibit greater vulnerability to heat-induced AKI if work is prolonged.

Use of Minimally Invasive Methods to Assess Fuel Utilization and Circadian Rhythms in Older Adults.

Aging is associated with multiple physiological changes that contribute synergistically and independently to physical disability and the risk of chronic disease. Although the etiology of age-related physical disability is complex and multifactorial, the decline in mitochondrial function appears to coincide with the progression of functional decline in many older adults. The reason why there is a decrease in mitochondrial function with aging remains elusive, but emerging science indicates that both fuel metabolism and circadian rhythms can influence mitochondrial function. Recent studies have established that circadian rhythms become disturbed with aging, and that disrupted circadian rhythms have pathological consequences that impact mitochondrial function and overlap with many age-associated chronic diseases. Current quantitative methods for direct assessment of mitochondrial function are invasive and typically require a muscle biopsy, which can pose difficulties with participant recruitment and study adherence, given the perceived levels of potential pain and risk. Thus, an innovative and relatively noninvasive protocol to assess changes in mitochondrial function at the cellular level and circadian patterns in older adults was adapted. Specifically, a real-time metabolic flux analyzer is used to assess the mitochondrial bioenergetic function of white blood cells under differential substrate availability. The expression of circadian clock genes in white blood cells to cross-correlate with the mitochondrial bioenergetics and circadian rhythm outcomes are also analyzed. It is believed that these innovative methodological approaches will aid future clinical trials by providing minimally invasive methods for studying mitochondrial substrate preference and circadian rhythms in older adults.

Suppression of FOXO1 attenuates inflamm-aging and improves liver function during aging.

The liver is a key metabolic organ that maintains whole-body nutrient homeostasis. Aging-induced liver function alterations contribute to systemic susceptibility to aging-related diseases. However, the molecular mechanisms of liver aging remain insufficiently understood. In this study, we performed bulk RNA-Seq and single-cell RNA-Seq analyses to investigate the underlying mechanisms of the aging-induced liver function changes. We found that liver inflammation, glucose intolerance, and liver fat deposition were aggravated in old mice. Aging significantly increased pro-inflammation in hepatic macrophages. Furthermore, we found that Kupffer cells (KCs) were the major driver to induce pro-inflammation in hepatic macrophages during aging. In KCs, aging significantly increased pro-inflammatory levels; in monocyte-derived macrophages (MDMs), aging had a limited effect on pro-inflammation but led to a functional quiescence in antigen presentation and phagosome process. In addition, we identified an aging-responsive KC-specific (ARKC) gene set that potentially mediates aging-induced pro-inflammation in KCs. Interestingly, FOXO1 activity was significantly increased in the liver of old mice. FOXO1 inhibition by AS1842856 significantly alleviated glucose intolerance, hepatic steatosis, and systemic inflammation in old mice. FOXO1 inhibition significantly attenuated aging-induced pro-inflammation in KCs partially through downregulation of ARKC genes. However, FOXO1 inhibition had a limited effect on aging-induced functional quiescence in MDMs. These results indicate that aging induces pro-inflammation in liver mainly through targeting KCs and FOXO1 is a key player in aging-induced pro-inflammation in KCs. Thus, FOXO1 could be a potential therapeutic target for the treatment of age-associated chronic diseases.

The Influence of Age-Associated Comorbidities on Responses to Combination Antiretroviral Therapy Among People Living with HIV, at the ART Clinic of Jimma Medical Center, Ethiopia: A Hospital-Based Nested Case-Control Study.

Despite the high prevalence of age-associated comorbidities in HIV patients in sub-Saharan Africa, there is a lack of data on their influence on treatment outcomes in HIV patients. Therefore, this study aimed to assess the impact of age-associated comorbidities on responses to antiretroviral therapy (ART) among people living with HIV. A hospital-based nested case-control study was conducted among adult HIV-infected patients at the Jimma Medical Center from January 3 to June 2, 2022. Data were recorded by interviewing the patients and their medical chart and analyzed using The Statistical Package for Social Science (SPSS) v. 23, and at p <0.05. The overall immunological and virologic failure rates were 13.8% and 13.4%, respectively. Being male [AOR = 3.079,95% CI (1.139-8.327)], having age-associated comorbidity [AOR:10.57,95% CI (2.810-39.779)], age ≥ 50 years [AOR = 2.855, 95% CI (1.023-7.9650)], alcohol intake [AOR = 3.648,95% CI (1.118-11.897)], and having a baseline CD4+ count of < 200 cells/uL [AOR:3.862, 95% CI (1.109-13.456) were an independent predictor of immunological failure; Whereas Being alcoholic [AOR:3.11, 95% CI (1.044-9.271)], having a baseline CD4+ count of < 200 cells/uL [AOR:5.11, 95% CI (1.547-16.892)], a low medication adherence [AOR:5.92, 95% CI (1.81-19.36)], bedridden baseline functional status [AOR:3.902, 95% CI (1.237-12.307)], and lack of cotrimoxazole prophylaxis [AOR:2.735,95% CI (1.084-6.902)] were found to be an independent predictor of virologic treatment failure, but being younger (age < 50 years) was protective for virologic failure. Out of the eight patients who were treated for HIV at least one patient had developed immunological and/or virological failure. Age-associated comorbid chronic non-communicable diseases highly influence immunological outcomes compared with virological outcomes. Health providers should pay attention to age-associated comorbidities, encourage lifestyle modifications, and counsel on medication adherence to improve clinical outcomes in patients with HIV.

Age-associated differences in the human lung extracellular matrix.

Extracellular matrix (ECM) remodeling has been associated with chronic lung diseases. However, information about specific age-associated differences in lung ECM is currently limited. In this study, we aimed to identify and localize age-associated ECM differences in human lungs using comprehensive transcriptomic, proteomic, and immunohistochemical analyses. Our previously identified age-associated gene expression signature of the lung was re-analyzed limiting it to an aging signature based on 270 control patients (37-80 years) and focused on the Matrisome core geneset using geneset enrichment analysis. To validate the age-associated transcriptomic differences on protein level, we compared the age-associated ECM genes (false discovery rate, FDR < 0.05) with a profile of age-associated proteins identified from a lung tissue proteomics dataset from nine control patients (49-76 years) (FDR < 0.05). Extensive immunohistochemical analysis was used to localize and semi-quantify the age-associated ECM differences in lung tissues from 62 control patients (18-82 years). Comparative analysis of transcriptomic and proteomic data identified seven ECM proteins with higher expression with age at both gene and protein levels: COL1A1, COL6A1, COL6A2, COL14A1, FBLN2, LTBP4, and LUM. With immunohistochemistry, we demonstrated higher protein levels with age for COL6A2 in whole tissue, parenchyma, airway wall, and blood vessel, for COL14A1 and LUM in bronchial epithelium, and COL1A1 in lung parenchyma. Our study revealed that higher age is associated with lung ECM remodeling, with specific differences occurring in defined regions within the lung. These differences may affect lung structure and physiology with aging and as such may increase susceptibility to developing chronic lung diseases.NEW & NOTEWORTHY We identified seven age-associated extracellular matrix (ECM) proteins, i.e., COL1A1, COL6A1, COL6A2 COL14A1, FBLN2, LTBP4, and LUM with higher transcript and protein levels in human lung tissue with age. Extensive immunohistochemical analysis revealed significant age-associated differences for COL6A2 in whole tissue, parenchyma, airway wall, and vessel, for COL14A1 and LUM in bronchial epithelium, and COL1A1 in parenchyma. Our findings lay a new foundation for the investigation of ECM differences in age-associated chronic lung diseases.

A cross-talk between sestrins, chronic inflammation and cellular senescence governs the development of age-associated sarcopenia and obesity.

The rapid increase in both the lifespan and proportion of older adults is accompanied by the unprecedented rise in age-associated chronic diseases, including sarcopenia and obesity. Aging is also manifested by increased susceptibility to multiple endogenous and exogenous stresses enabling such chronic conditions to develop. Among the main physiological regulators of cellular adaption to various stress stimuli, such as DNA damage, hypoxia, and oxidative stress, are sestrins (Sesns), a family of three evolutionarily conserved proteins, Sesn1, 2, and 3. Age-associated sarcopenia and obesity are characterized by two key processes: (i) accumulation of senescent cells in the skeletal muscle and adipose tissue and (ii) creation of a systemic, chronic, low-grade inflammation (SCLGI). Presumably, failed SCLGI resolution governs the development of these chronic conditions. Noteworthy, Sesns activate senolytics, which are agents that selectively eliminate senescent cells, as well as specialized pro-resolving mediators, which are factors that physiologically provide inflammation resolution. Sesns reveal clear beneficial effects in pre-clinical models of sarcopenia and obesity. Based on these observations, we propose a novel treatment strategy for age-associated sarcopenia and obesity, complementary to the conventional therapeutic modalities: Sesn activation, SCLGI resolution, and senescent cell elimination.

Equine osteoarthritis modifies fatty acid signatures in synovial fluid and its extracellular vesicles

BackgroundIndividual fatty acids (FAs) and their derivatives (lipid mediators) with pro-inflammatory or dual anti-inflammatory and pro-resolving properties have potential to influence the health of joint tissues. Osteoarthritis (OA) is an age-associated chronic joint disease that can be featured with altered FA composition in the synovial fluid (SF) of human patients. The counts and cargo of extracellular vesicles (EVs), membrane-bound particles released by synovial joint cells and transporting bioactive lipids, can also be modified by OA. The detailed FA signatures of SF and its EVs have remained unexplored in the horse — a well-recognized veterinary model for OA research.MethodsThe aim of the present study was to compare the FA profiles in equine SF and its ultracentrifuged EV fraction between control, contralateral, and OA metacarpophalangeal joints (n = 8/group). The FA profiles of total lipids were determined by gas chromatography and the data compared with univariate and multivariate analyses.ResultsThe data revealed distinct FA profiles in SF and its EV-enriched pellet that were modified by naturally occurring equine OA. Regarding SFs, linoleic acid (generalized linear model, p = 0.0006), myristic acid (p = 0.003), palmitoleic acid (p < 0.0005), and n-3/n-6 polyunsaturated FA ratio (p < 0.0005) were among the important variables that separated OA from control samples. In EV-enriched pellets, saturated FAs palmitic acid (p = 0.020), stearic acid (p = 0.002), and behenic acid (p = 0.003) indicated OA. The observed FA modifications are potentially detrimental and could contribute to inflammatory processes and cartilage degradation in OA.ConclusionsEquine OA joints can be distinguished from normal joints based on their FA signatures in SF and its EV-enriched pellet. Clarifying the roles of SF and EV FA compositions in the pathogenesis of OA and their potential as joint disease biomarkers and therapeutic targets warrants future studies.

Long-term intensive endurance exercise training is associated to reduced markers of cellular senescence in the colon mucosa of older adults

Regular endurance exercise training is an effective intervention for the maintenance of metabolic health and the prevention of many age-associated chronic diseases. Several metabolic and inflammatory factors are involved in the health-promoting effects of exercise training, but regulatory mechanisms remain poorly understood. Cellular senescence—a state of irreversible growth arrest—is considered a basic mechanism of aging. Senescent cells accumulate over time and promote a variety of age-related pathologies from neurodegenerative disorders to cancer. Whether long-term intensive exercise training affect the accumulation of age-associated cellular senescence is still unclear. Here, we show that the classical senescence markers p16 and IL-6 were markedly higher in the colon mucosa of middle-aged and older overweight adults than in young sedentary individuals, but this upregulation was significantly blunted in age-matched endurance runners. Interestingly, we observe a linear correlation between the level of p16 and the triglycerides to HDL ratio, a marker of colon adenoma risk and cardiometabolic dysfunction. Our data suggest that chronic high-volume high-intensity endurance exercise can play a role in preventing the accumulation of senescent cells in cancer-prone tissues like colon mucosa with age. Future studies are warranted to elucidate if other tissues are also affected, and what are the molecular and cellular mechanisms that mediate the senopreventative effects of different forms of exercise training.

Photobiomodulation therapy mitigates cardiovascular aging and improves survival.

Photobiomodulation (PBM) therapy, a form of low-dose light therapy, has been noted to be effective in several age-associated chronic diseases such as hypertension and atherosclerosis. Here, we examined the effects of PBM therapy on age-associated cardiovascular changes in a mouse model of accelerated cardiac aging. Fourteen months old Adenylyl cyclase type VIII (AC8) overexpressing transgenic mice (n = 8) and their wild-type (WT) littermates (n = 8) were treated with daily exposure to Near-Infrared Light (850 nm) at 25 mW/cm2 for 2 min each weekday for a total dose of 1 Einstein (4.5 p.J/cm2 or fluence 3 J/cm2 ) and compared to untreated controls over an 8-month period. PBM therapy was administered for 3.5 months (Early Treatment period), paused, due to Covid-19 restrictions for the following 3 months, and restarted again for 1.5 months. Serial echocardiography and gait analyses were performed at monthly intervals, and serum TGF-β1 levels were assessed following sacrifice. During the Early Treatment period PBM treatments: reduced the age-associated increases in left ventricular (LV) mass in both genotypes (p = 0.0003), reduced the LV end-diastolic volume (EDV) in AC8 (p = 0.04); and reduced the left atrial dimension in both genotypes (p = 0.02). PBM treatments substantially increased the LV ejection fraction (p = 0.03), reduced the aortic wall stiffness (p = 0.001), and improved gait symmetry, an index of neuro-muscular coordination (p = 0.005). The effects of PBM treatments, measured following the pause, persisted. Total TGF-β1 levels were significantly increased in circulation (serum) in AC8 following PBM treatments (p = 0.01). We observed a striking increase in cumulative survival in PBM-treated AC8 mice (100%; p = 0.01) compared to untreated AC8 mice (43%). PBM treatment mitigated age-associated cardiovascular remodeling and reduced cardiac function, improved neuromuscular coordination, and increased longevity in an experimental animal model. These responses correlate with increased TGF-β1 in circulation. Future mechanistic and dose optimization studies are necessary to assess these anti-aging effects of PBM, and validation in future controlled human studies is required for effective clinical translation.

Untargeted muscle tissue metabolites profiling in young, adult, and old rats supplemented with tocotrienol-rich fraction.

The greatest significant influence on human life span and health is inevitable ageing. One of the distinguishing characteristics of ageing is the gradual decrease of muscle mass and physical function. There has been growing evidence that tocotrienol can guard against age-associated chronic diseases and metabolic disorders. This study aimed to elucidate the effects of tocotrienol-rich fraction (TRF) on muscle metabolomes and metabolic pathways in ageing Sprague Dawley (SD) rats. Three months, 9 months, and 21 months old male SD rats were divided into control and treated groups with 10 rats per group. Rats in control and treated groups were given 60 mg/kg body weight/day of palm olein and 60 mg/kg body weight/day of TRF, respectively, via oral gavage for 3 months. Muscle performance was assessed at 0 and 3 months of treatment by measuring muscle strength and function. Our results showed that TRF treatment caused a significant increase in the swimming time of the young rats. Comparison in the control groups showed that metabolites involved in lipid metabolisms such as L-palmitoyl carnitine and decanoyl carnitine were increased in ageing. In contrast, several metabolites, such as 3-phosphoglyceric acid, aspartic acid and aspartyl phenylalanine were decreased. These findings indicated that muscle metabolomes involved in lipid metabolism were upregulated in aged rats. In contrast, the metabolites involved in energy and amino acid metabolism were significantly downregulated. Comparison in the TRF-supplemented groups showed an upregulation of metabolites involved in energy and amino acid metabolism. Metabolites such as N6-methyl adenosine, spermine, phenylalanine, tryptophan, aspartic acid, histidine, and N-acetyl neuraminic acid were up-regulated, indicating promotion of amino acid synthesis and muscle regeneration. Energy metabolism was also improved in adult and old rats with TRF supplementation as indicated by the upregulation of nicotinamide adenine dinucleotide and glycerol 3-phosphate compared to the control group. In conclusion, the mechanism underlying the changes in skeletal muscle mass and functions in ageing was related to carbohydrate, lipid and amino acid metabolism. Tocotrienol supplementation showed beneficial effects in alleviating energy and amino acid synthesis that may promote the regeneration and renewal of skeletal muscle in ageing rats.

Antioxidant Effects of a Polyphenol-Rich Dietary Supplement Incorporating Pinus massoniana Bark Extract in Healthy Older Adults: A Two-Arm, Parallel Group, Randomized Placebo-Controlled Trial.

Oxidative stress is a key physiological phenomenon underpinning the ageing process and plays a major developmental role in age-associated chronic diseases. This study investigated the antioxidant effects of a polyphenol-rich dietary supplement containing Pinus massoniana bark extract (PMBE) in healthy older adults. In a double-blinded, placebo-controlled clinical trial, participants were randomised (in a 1:1 ratio) to receive a 50 mL/day dietary supplement containing placebo (0 mg PMBE) or PMBE (1322 mg PMBE) for 12 weeks. The primary outcome was fasting plasma malondialdehyde (MDA) concentrations and secondary outcomes were plasma inflammatory markers. MDA concentrations significantly reduced following PMBE for 6 weeks (−1.19 nmol/mL, 95%CI −1.62, −0.75, p < 0.001) and 12 weeks (−1.35 nmol/mL, 95%CI −1.74, −0.96, p < 0.001) compared to baseline. MDA did not significantly change after the placebo. MDA levels at 6 and 12 weeks were significantly lower following PMBE compared to placebo (p < 0.001). At 12 weeks in the PMBE group, fibrinogen concentrations significantly reduced (−0.25 g/L, 95%CI −0.39, −0.11; p < 0.0001) and interleukin-6 significantly increased compared to placebo (0.30 pg/mL, 95%CI 0.02, 0.59; p < 0.05). PMBE in a polyphenol-rich dietary supplement reduced oxidative stress in healthy older adults. Further studies are warranted to investigate the antioxidant capacity of PMBE in conditions with heightened oxidative stress, such as osteoarthritis, hypertension, type 2 diabetes, or other lifestyle related diseases.

Mediterranean Diet on Sleep: A Health Alliance

The Mediterranean diet is a plant-based, antioxidant-rich, unsaturated fat dietary pattern that has been consistently associated with lower rates of noncommunicable diseases and total mortality, so that it is considered one of the healthiest dietary patterns. Clinical trials and mechanistic studies have demonstrated that the Mediterranean diet and its peculiar foods and nutrients exert beneficial effects against inflammation, oxidative stress, dysmetabolism, vascular dysfunction, adiposity, senescence, cognitive decline, neurodegeneration, and tumorigenesis, thus preventing age-associated chronic diseases and improving wellbeing and health. Nocturnal sleep is an essential physiological function, whose alteration is associated with health outcomes and chronic diseases. Scientific evidence suggests that diet and sleep are related in a bidirectional relationship, and the understanding of this association is important given their role in disease prevention. In this review, we surveyed the literature concerning the current state of evidence from epidemiological studies on the impact of the Mediterranean diet on nighttime sleep quantity and quality. The available studies indicate that greater adherence to the Mediterranean diet is associated with adequate sleep duration and with several indicators of better sleep quality. Potential mechanisms mediating the effect of the Mediterranean diet and its foods and nutrients on sleep are described, and gap-in-knowledge and new research agenda to corroborate findings are discussed.

Connecting aging biology and inflammation in the omics era.

Aging is characterized by the accumulation of damage to macromolecules and cell architecture that triggers a proinflammatory state in blood and solid tissues, termed inflammaging. Inflammaging has been implicated in the pathogenesis of many age-associated chronic diseases as well as loss of physical and cognitive function. The search for mechanisms that underlie inflammaging focused initially on the hallmarks of aging, but it is rapidly expanding in multiple directions. Here, we discuss the threads connecting cellular senescence and mitochondrial dysfunction to impaired mitophagy and DNA damage, which may act as a hub for inflammaging. We explore the emerging multi-omics efforts that aspire to define the complexity of inflammaging — and identify molecular signatures and novel targets for interventions aimed at counteracting excessive inflammation and its deleterious consequences while preserving the physiological immune response. Finally, we review the emerging evidence that inflammation is involved in brain aging and neurodegenerative diseases. Our goal is to broaden the research agenda for inflammaging with an eye on new therapeutic opportunities.

New Horizons in the Treatment of Age-Associated Obesity, Sarcopenia and Osteoporosis.

The rapid increase in both the lifespan and proportion of older adults in developed countries is accompanied by the dramatic growth of age-associated chronic diseases, including obesity, sarcopenia, and osteoporosis. Hence, prevention and treatment of age-associated chronic diseases has become increasingly urgent. The key to achieving this goal is a better understanding of the mechanisms underlying their pathophysiology, some aspects of which, despite extensive investigation, are still not fully understood. Aging, obesity, sarcopenia, and osteoporosis are characterized by the creation of a systemic, chronic, low-grade inflammation (SCLGI). The common mechanisms that govern the development of these chronic conditions include a failed resolution of inflammation. Physiologically, the process of inflammation resolution is provided mainly by specialized pro-resolving mediators (SPMs) acting via cognate G protein-coupled receptors (GPCRs). Noteworthy, SPM levels and the expression of their receptors are significantly reduced in aging and the associated chronic disorders. In preclinical studies, supplementation of SPMs or their stable, small-molecule SPM mimetics and receptor agonists reveals clear beneficial effects in inflammation-related obesity and sarcopenic and osteoporotic conditions, suggesting a translational potential. Age-associated chronic disorders are also characterized by gut dysbiosis and the accumulation of senescent cells in the adipose tissue, skeletal muscle, and bones. Based on these findings, we propose SCLGI resolution as a novel strategy for the prevention/treatment of age-associated obesity, sarcopenia, and osteoporosis. Our approach entails the enhancement of inflammation resolution by SPM mimetics and receptor agonists in concert with probiotics/prebiotics and compounds that eliminate senescent cells and their pro-inflammatory activity.

Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain

BackgroundAltered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina.MethodsUsing fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing.ResultsWe show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota.ConclusionsThese findings demonstrate that the aging gut microbiota drives detrimental changes in the gut–brain and gut–retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life.A2ymqPEb5xjd37hjwT7XDQVideo abstractGraphical abstract

Trapping Methylglyoxal by Taxifolin and Its Metabolites in Mice

Trapping of methylglyoxal (MGO), an important precursor of advanced glycation end products (AGEs), is considered an effective therapy for alleviating AGE-induced chronic metabolic diseases. In this paper, taxifolin (Tax) was first found to effectively trap MGO by forming mono- and di-MGO adducts under in vitro conditions. In addition, the mechanism of trapping MGO by Tax was also studied in vivo. Tax was demonstrated to efficiently trap endogenous MGO via formation of mono-MGO adducts in urine and fecal samples of C57BL/6J mice after oral administration of Tax and MGO. Mono-MGO adducts of Tax metabolites, including methylated Tax, aromadendrin, quercetin, and isorhamnetin, were identified in C57BL/6J mice urine and fecal samples by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS). One mono-MGO-Tax was purified from the in vitro reaction mixture, and its structure was elucidated as 6-MGO-Tax based on the analysis of UHPLC-QTOF-MS/MS and detailed nuclear magnetic resonance (NMR) data. Quantification studies demonstrated that Tax and its metabolites trapped MGO in a dose-dependent manner in C57BL/6J mice urine and fecal samples. Furthermore, we also detected mono-MGO adducts of Tax and methylated Tax in urine and fecal samples of diabetic db/db mice after oral administration of Tax. Taken together, our results demonstrated that dietary Tax has the potential to detoxify MGO and treat AGE-associated chronic diseases.

Healthy Aging and Dietary Patterns.

A number of factors contribute to the complex process of aging, which finally define whether someone will or not develop age-associated chronic diseases in late life. These determinants comprise genetic susceptibility as well as various behavioral, environmental, and dietary factors, all of which have been shown to influence specific pathways regulating the aging process and the extension of life, which makes longevity a multidimensional phenomenon. Although a “miraculous elixir” or a “nutrition pill” are not plausible, researchers agree on the notion that nutritional factors have major impact on the risk of age-associated chronic non-communicable diseases and mortality. In recent years nutrition research in relation to health outcomes has considerably changed from focusing exclusively on single nutrients to considering combinations of foods rather than nutrients in isolation. Although research on specific nutrients is scientifically valid providing crucial evidence on the mechanisms by which nutrition impacts health, the recent switch targeting the multifaceted synergistic interplay among nutrients, other dietary constituents, and whole foods, has promoted emerging interest on the actions of total dietary patterns. This narrative review aims to describe some specific dietary patterns with evidence of associations with reduction in the incidence of chronic diseases allowing older adults to live a long-lasting and healthier life, and confirming the powerful impact nutrition can exert on healthy aging.

Targeting the molecular & cellular pillars of human aging with exercise.

Biological aging is the main driver of age-associated chronic diseases. In 2014, the United States National Institute of Aging (NIA) sponsored a meeting between several investigators in the field of aging biology, who identified seven biological pillars of aging and a consensus review, "Geroscience: Linking Aging to Chronic Disease," was published. The pillars of aging demonstrated the conservation of aging pathways in diverse model organisms and thus represent a useful framework with which to study human aging. In this present review, we revisit the seven pillars of aging from the perspective of exercise and discuss how regular physical exercise can modulate these pillars to stave off age-related chronic diseases and maintain functional capacity.

The Challenge of Medication-Induced Dry Mouth in Residential Aged Care.

With a reported prevalence between 20% and 30%, dry mouth is more common among older people than any other age group. The major risk factor for dry mouth is polypharmacy. Older people take more medications than any other age group, not only for symptomatic relief of various age-associated chronic diseases, but also to reduce the likelihood of the complications that may arise from those conditions. Most aged care residents take even more medications than older people who are living in their own homes. The greater the number of medications taken, the greater the associated anticholinergic burden, and the more likely it is that the individual will suffer from dry mouth. The condition not only affects the dentition and ability to wear dentures, but also the sufferers’ quality of life. Treating dry mouth is a considerable challenge for clinicians. As medication use is by far the most important risk factor, there is a need for pharmacists, doctors and dentists to work together to prevent this from occurring. Medication review and deprescribing is a key strategy, but there have not yet been any randomised control trials of its efficacy in reducing the occurrence of dry mouth.

Zinc status, insulin resistance and glycoxidative stress in elderly subjects with type 2 diabetes mellitus.

Zinc deficiencies have been reported in numerous pathologies, such as diabetes mellitus, but also in the physiological process of ageing. Similarly, the end products of glycoxidation processes, advanced glycation end products (AGEs), are damaging compounds, a myriad of reports linking them to the development and progression of several age-associated chronic diseases. The aim of the present study was to analyze the relationships between zinc status, glycoxidative stress and insulin resistance (IR) in elderly subjects with type 2 diabetes mellitus (T2DM). A group of 52 non-smoking subjects (9 men and 43 women, aged 65-83 years) were enrolled in this cross-sectional study: 27 patients with T2DM, and 25 apparently healthy control subjects. Serum zinc (Zn) levels were assessed using a commercial kit based on an end-point colorimetric method, and serum AGEs were evaluated with a fluorimetric analytic procedure. The calculated glucose-to-zinc ratio (Gly/Zn), insulin-to-zinc ratio (Ins/Zn) and insulin-zinc resistance index (HOMA-IR/Zn) were further used to study the associations between serum Zn levels, secretory function of β-pancreatic cells and AGEs. T2DM patients presented significantly higher serum insulin and Zn levels, as compared to the controls. We found a significant inverse correlation between Zn and AGEs, and a strong positive correlation between AGEs and the Gly/Zn ratio, suggesting that both Zn and AGEs are biomarkers that could reflect the persistence of hyperglycemia. We identified new surrogate biomarkers useful for the assessment of glycemic control with great potential for the development of preventive and therapeutic strategies for elderly diabetics, based on the evaluation of serum Zn levels.