Age-related Diseases Research Articles

Inhibition of mTOR prevents glucotoxicity-mediated increase of SA-beta-gal, p16INK4a, and insulin hypersecretion, without restoring electrical features of mouse pancreatic islets.

An over-activation of the mechanistic target of rapamycin (mTOR) pathway promotes senescence and age-related diseases like type 2 diabetes. Besides, the regenerative potential of pancreatic islets deteriorates with aging. Nevertheless, the role of mTOR on senescence promoted by metabolic stress in islet cells as well as its relevance for electrophysiological aspects is not yet known. Here, we investigated whether parameters suggested to be indicative for senescence are induced in vitro in mouse islet cells by glucotoxicity and if mTOR inhibition plays a protective role against this. Islet cells exhibit a significant increase (~ 76%) in senescence-associated beta-galactosidase (SA-beta-gal) activity after exposure to glucotoxicity for 72h. Glucotoxicity does not markedly influence p16INK4a protein within 72h, but p16INK4a levels increase significantly after a 7-days incubation period. mTOR inhibition with a low rapamycin concentration (1nM) entirely prevents the glucotoxicity-mediated increase of SA-beta-gal and p16INK4a. At the functional level, reactive oxygen species, calcium homeostasis, and electrical activity are disturbed by glucotoxicity, and rapamycin fails to prevent this. In contrast, rapamycin significantly attenuates the insulin hypersecretion promoted by glucotoxicity by modifying the mRNA levels of Vamp2 and Snap25 genes, related to insulin exocytosis. Our data indicate an influence of glucotoxicity on pancreatic islet-cell senescence and a reduction of the senescence markers by mTOR inhibition, which is relevant to preserve the regenerative potential of the islets. Decreasing the influence of mTOR on islet cells exposed to glucotoxicity attenuates insulin hypersecretion, but is not sufficient to prevent electrophysiological disturbances, indicating the involvement of mTOR-independent mechanisms.

The potential protective role of vitamin D and calcium supplements in reducing cardiovascular disease risk among elderly patients with osteopenia.

Cardiovascular disease and low bone mineral density are major health problems in the elderly. These two conditions are considered independent of each other and age-related diseases. The aim of this study is to investigate the association between low bone mineral density (BMD) and cardiovascular disease (CVD) incidents, and the effect of vitamin D and calcium supplement on the incidence of CVD in patients with low BMD. A total of 1047 patients (597 females/450 males) with the age of 65years and more were diagnosed with osteopenia for 13years or more. The study also included 220 patients (107 females/113 males) with osteopenia who already took calcium and vitamin D continually since their diagnosis. BMD was measured by dual-energy X-ray absorptiometry. The incidence of any cardiovascular diseases in the study patients and the presence of corresponding risk factors were collected and analyzed. In both elderly Arab females and males, there was an association between total hip and femoral neck BMD and the possibility to have CVD. On the other hand, the results showed that patients who use calcium and vitamin D supplements showed a significant reduction in the incidence of CVD comparing to the non-treated patients. Low total hip and femoral neck BMD were associated with a higher chance to have CVD incidents in both elderly Arab males and females; moreover, calcium and vitamin D supplements have a possible protective role in reducing cardiovascular disease in elderly patients with osteopenia.

Age-related dysregulation of the retinal transcriptome in African turquoise killifish.

Age-related vision loss caused by retinal neurodegenerative pathologies is becoming more prevalent in our ageing society. To understand the physiological and molecular impact of ageing on retinal homeostasis, we used the short-lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) ageing hallmarks and vision loss. Bulk and single-cell RNA-sequencing (scRNAseq) of three age groups (6-, 12-, and 18-week-old) identified transcriptional ageing fingerprints in the killifish retina, unveiling pathways also identified in the aged brain, including oxidative stress, gliosis, and inflammageing. These findings were comparable to observations in the ageing mouse retina. Additionally, transcriptional changes in genes related to retinal diseases, such as glaucoma and age-related macular degeneration, were observed. The cellular heterogeneity in the killifish retina was characterized, confirming the presence of all typical vertebrate retinal cell types. Data integration from age-matched samples between the bulk and scRNAseq experiments revealed a loss of cellular specificity in gene expression upon ageing, suggesting potential disruption in transcriptional homeostasis. Differential expression analysis within the identified cell types highlighted the role of glial/immune cells as important stress regulators during ageing. Our work emphasizes the value of the fast-ageing killifish in elucidating molecular signatures in age-associated retinal disease and vision decline. This study contributes to the understanding of how age-related changes in molecular pathways may impact CNS health, providing insights that may inform future therapeutic strategies for age-related pathologies.

Discrimination of Aspartic and Isoaspartic Acid Residues in Peptides by Tandem Mass Spectrometry with Hydrogen Attachment Dissociation.

Long-lived proteins undergo chemical modifications that can cause age-related diseases. Among these chemical modifications, isomerization is the most difficult to identify. Isomerization often occurs at the aspartic acid (Asp) residues. In this study, we used tandem mass spectrometry equipped with a newly developed ion activation method, hydrogen attachment dissociation (HAD), to analyze peptides containing Asp isomers. Although HAD preferentially produces [cn + 2H]+ and [zm + 2H]+ via N-Cα bond cleavage, [cn + 58 + 2H]+ and [zm - 58 + 2H]+ originate from the fragmentation of the isoAsp residue. Notably, [cn + 58 + 2H]+ and [zm - 58 + 2H]+ could be used as diagnostic fragment ions for the isoAsp residue because these fragment ions did not originate from the Asp residue. The detailed fragmentation mechanism was investigated by computational analysis using density functional theory. According to the results, hydrogen attachment to the carbonyl oxygen in the isoAsp residue results in the Cα-Cβ bond cleavage. The experimental and theoretical joint study indicates that the present method allows us to discriminate Asp and isoAsp residues, including site identification of the isoAsp residue. Moreover, we demonstrated that the molar ratio of peptide isomers in the mixture could be estimated from their fragment ion abundance. Therefore, tandem mass spectrometry with HAD is a useful method for the rapid discrimination and semiquantitative analysis of peptides containing isoAsp residues.

Prediction of Age-Related MicroRNA Signature in Mesenchymal Stem Cells by using Computational Methods.

Aging is a phenomenon which occurs over time and leads to the decay of living organisms. During the progression of aging, some age-associated diseases including cardiovascular disease, cancers, and neurological, mental, and physical disorders could develop. Genetic and epigenetic factors like microRNAs, as one of the post-transcriptional regulators of genes, play important roles in senescence. The self-renewal and differentiation capacity of mesenchymal stem cells makes them good candidates for regenerative medicine. The objective of this study is to evaluate senescence-related miRNAs in human MSCs using bioinformatics analysis. In this study, the Gene Expression Omnibus (GEO) database was used to investigate the senescence-related genome profile. Then, down-regulated genes were selected for further bioinformatics analysis with the assumption that their decreased expression is associated with an increased aging process. Considering that miRNAs can interfere in gene expression, miRNAs complementary to these genes were identified using bioinformatics software. Through bioinformatics analysis, we predicted hsa-miR-590-3p, hsa-miR-10b-3p, hsamiR- 548 family, hsa-miR-144-3p, and hsa-miR-30b-5p which involve in cellular senescence and the aging of human MSCs. miRNA mimics or anti-miRNA agents have the potential to be used as anti-aging tools for MSCs.

Study of the Relation between Aging and Pesticides: A Review

Aims: The main aim of this study was to use specific data from the literature on ageing, correlating this with the pesticide contamination, in order to understand the relationship with an increasingly ageing population. Study Design: A systematic review was performed. Place and Duration of Study: Laboratory of Biomathematics of the Federal University of Alfenas, Minas Gerais State, Brazil, between April 2023 and August 2023. Methodology: A systematic search of articles was performed using the CAPES Periodic platform, a searcher from the Education Ministry of Brazil that contains Web of Science, Scopus, MedLine, from August 2020 to May 2023. For this review, the subject’s “aging theory”; “neuroscience and pathologies to aging”; “aging and aging-associated changes”; “pesticides and pesticide toxicity”; “pesticide toxicity and neurotoxicity”; “longevity and healthy aging”; “aging human and pesticides” were searched together using the type of material “articles” in English language. Some articles about “population growth”; “world population”; “population-aging” were used for epistemological composition of this work content subjects. Results: From the 19.720 articles after the exclusion and the inclusion criteria made with the subjects most pertinent to the objectives of this work; 19.570 articles were excluded, remaining 150 ones, of which 116 were qualitative in scope and 34 quantitative. Conclusion: The complex relationship between the pesticide contamination and the condition of the exposed individual may be associated with premature ageing and a greater susceptibility to debilitating age-related diseases. Although technology is increasingly improved in its innovations, health and environmental regulations have not been able to rid the production processes of their potential to pollute the environment and cause health problems for those exposed to them.

Intermittent Metabolic Switching and Vascular Cognitive Impairment.

Intermittent fasting (IF), a dietary pattern alternating between eating and fasting periods within a 24-hour cycle, has garnered recognition for its potential to enhance both healthspan and lifespan in animal models and humans. It also shows promise in alleviating age-related diseases, including neurodegeneration. Vascular cognitive impairment (VCI) spans a severity range from mild cognitive deficits to severe cognitive deficits and loss of function in vascular dementia. Chronic cerebral hypoperfusion has emerged as a significant contributor to VCI, instigating vascular pathologies such as microbleeds, blood-brain barrier dysfunction, neuronal loss and white matter lesions. Preclinical studies in rodents strongly suggest that IF has the potential to attenuate pathological mechanisms, including excitotoxicity, oxidative stress, inflammation, and cell death pathways in VCI models. Hence, this supports evaluating IF in clinical trials for both existing and at-risk VCI patients. This review compiles existing data supporting IF's potential in treating VCI-related vascular and neuronal pathologies, emphasizing the mechanisms by which IF may mitigate these issues. Hence providing a comprehensive overview of the available data supporting IF's potential in treating VCI by emphasizing the underlying mechanisms that make IF a promising intervention for VCI.

SAPPα Peptide Promotes Damaged Microglia to Clear Alzheimer's Amyloid-β via Restoring Mitochondrial Function.

Alzheimer's disease (AD) is an age-related neurodegenerative disease with amyloid-β (Aβ) deposition as the main pathological feature. It's an important challenge to find new ways to clear Aβ from Brain. The soluble amyloid precursor protein α (sAPPα) is a neuroprotective protein and can attenuate neuronal damage, including toxic Aβ. However, the regulatory role of sAPPα in non-neuronal cells, such as microglia, is less reported and controversial. Here, we showed that sAPPα promoted the phagocytosis and degradation of Aβ in both normal and damaged microglia. Moreover, the function of damaged microglia was improved by the sAPPα through normalizing mitochondrial function. Furthermore, the results of molecular docking simulation showed that sAPPα had a good affinity with Aβ. We preliminarily reveal that sAPPα is similar to antibodies and can participate in the regulation of microglia phagocytosis and degradation of Aβ after binding to Aβ. sAPPα is expected to be a mild and safe peptide drug or drug carrier for AD.

Biomarker signatures associated with ageing free of major chronic diseases: results from a population-based sample of the EPIC-Potsdam cohort.

A number of biomarkers denoting various pathophysiological pathways have been implicated in the aetiology and risk of age-related diseases. Hence, the combined impact of multiple biomarkers in relation to ageing free of major chronic diseases, such as cancer, cardiovascular disease and type 2 diabetes, has not been sufficiently explored. We measured concentrations of 13 biomarkers in a random subcohort of 2,500 participants in the European Prospective Investigation into Cancer and Nutrition Potsdam study. Chronic disease-free ageing was defined as reaching the age of 70years within study follow-up without major chronic diseases, including cardiovascular disease, type 2 diabetes or cancer. Using a novel machine-learning technique, we aimed to identify biomarker clusters and explore their association with chronic disease-free ageing in multivariable-adjusted logistic regression analysis taking socio-demographic, lifestyle and anthropometric factors into account. Of the participants who reached the age of 70years, 321 met our criteria for chronic-disease free ageing. Machine learning analysis identified three distinct biomarker clusters, among which a signature characterised by high concentrations of high-density lipoprotein cholesterol, adiponectin and insulin-like growth factor-binding protein 2 and low concentrations of triglycerides was associated with highest odds for ageing free of major chronic diseases. After multivariable adjustment, the association was attenuated by socio-demographic, lifestyle and adiposity indicators, pointing to the relative importance of these factors as determinants of healthy ageing. These data underline the importance of exploring combinations of biomarkers rather than single molecules in understanding complex biological pathways underpinning healthy ageing.

Prototyping an Ontological Framework for Cellular Senescence Mechanisms: A Homeostasis Imbalance Perspective

Although cellular senescence is a key factor in organismal aging, with both positive and negative effects on individuals, its mechanisms remain largely unknown. Thus, integrating knowledge is essential to explain how cellular senescence manifests in tissue damage and age-related diseases. Here, we propose an ontological model that organizes knowledge of cellular senescence in a computer-readable form. We manually annotated and defined cellular senescence processes, molecules, anatomical structures, phenotypes, and other entities based on the Homeostasis Imbalance Process ontology (HOIP). We described the mechanisms as causal relationships of processes and modelled a homeostatic imbalance between stress and stress response in cellular senescence for a unified framework. HOIP was assessed formally, and the relationships between cellular senescence and diseases were inferred for higher-order knowledge processing. We visualized cellular senescence processes to support knowledge utilization. Our study provides a knowledge base to help elucidate mechanisms linking cellular and organismal aging.

Hyper-physiologic mechanical cues, as an osteoarthritis disease-relevant environmental perturbation, cause a critical shift in set points of methylation at transcriptionally active CpG sites in neo-cartilage organoids

BackgroundOsteoarthritis (OA) is a complex, age-related multifactorial degenerative disease of diarthrodial joints marked by impaired mobility, joint stiffness, pain, and a significant decrease in quality of life. Among other risk factors, such as genetics and age, hyper-physiological mechanical cues are known to play a critical role in the onset and progression of the disease (Guilak in Best Pract Res Clin Rheumatol 25:815–823, 2011). It has been shown that post-mitotic cells, such as articular chondrocytes, heavily rely on methylation at CpG sites to adapt to environmental cues and maintain phenotypic plasticity. However, these long-lasting adaptations may eventually have a negative impact on cellular performance. We hypothesize that hyper-physiologic mechanical loading leads to the accumulation of altered epigenetic markers in articular chondrocytes, resulting in a loss of the tightly regulated balance of gene expression that leads to a dysregulated state characteristic of the OA disease state.ResultsWe showed that hyper-physiological loading evokes consistent changes in CpGs associated with expression changes (ML-tCpGs) in ITGA5, CAV1, and CD44, among other genes, which together act in pathways such as anatomical structure morphogenesis (GO:0009653) and response to wound healing (GO:0042060). Moreover, by comparing the ML-tCpGs and their associated pathways to tCpGs in OA pathophysiology (OA-tCpGs), we observed a modest but particular interconnected overlap with notable genes such as CD44 and ITGA5. These genes could indeed represent lasting detrimental changes to the phenotypic state of chondrocytes due to mechanical perturbations that occurred earlier in life. The latter is further suggested by the association between methylation levels of ML-tCpGs mapped to CD44 and OA severity.ConclusionOur findings confirm that hyper-physiological mechanical cues evoke changes to the methylome-wide landscape of chondrocytes, concomitant with detrimental changes in positional gene expression levels (ML-tCpGs). Since CAV1, ITGA5, and CD44 are subject to such changes and are central and overlapping with OA-tCpGs of primary chondrocytes, we propose that accumulation of hyper-physiological mechanical cues can evoke long-lasting, detrimental changes in set points of gene expression that influence the phenotypic healthy state of chondrocytes. Future studies are necessary to confirm this hypothesis.

Senotherapeutic Peptide 14 Suppresses Th1 and M1 Human T Cell and Monocyte Subsets In Vitro

Inflammation contributes to the onset and exacerbation of numerous age-related diseases, often manifesting as a chronic condition during aging. Given that cellular senescence fosters local and systemic inflammation, senotherapeutic interventions could potentially aid in managing or even reducing inflammation. Here, we investigated the immunomodulatory effects of the senotherapeutic Peptide 14 (Pep 14) in human peripheral blood mononuclear cells (PBMCs), monocytes, and macrophages. We found that, despite failing to significantly influence T cell activation and proliferation, the peptide promoted a Th2/Treg gene expression and cytokine signature in PBMCs, characterized by increased expression of the transcription factors GATA3 and FOXP3, as well as the cytokines IL-4 and IL-10. These observations were partially confirmed through ELISA, in which we observed increased IL-10 release by resting and PHA-stimulated PBMCs. In monocytes from the U-937 cell line, Pep 14 induced apoptosis in lipopolysaccharide (LPS)-stimulated cells and upregulated IL-10 expression. Furthermore, Pep 14 prevented LPS-induced activation and promoted an M2-like polarization in U-937-derived macrophages, evidenced by decreased expression of M1 markers and increased expression of M2 markers. We also showed that the conditioned media from Pep 14-treated macrophages enhanced fibroblast migration, indicative of a functional M2 phenotype. Taken together, our findings suggest that Pep 14 modulates immune cell function towards an anti-inflammatory and regenerative phenotype, highlighting its potential as a therapeutic intervention to alleviate immunosenescence-associated dysregulation.

Therapeutic potential of berries in age-related neurological disorders

Aging significantly impacts several age-related neurological problems, such as stroke, brain tumors, oxidative stress, neurodegenerative diseases (Alzheimer’s, Parkinson’s, and dementia), neuroinflammation, and neurotoxicity. Current treatments for these conditions often come with side effects like hallucinations, dyskinesia, nausea, diarrhea, and gastrointestinal distress. Given the widespread availability and cultural acceptance of natural remedies, research is exploring the potential effectiveness of plants in common medicines. The ancient medical system used many botanical drugs and medicinal plants to treat a wide range of diseases, including age-related neurological problems. According to current clinical investigations, berries improve motor and cognitive functions and protect against age-related neurodegenerative diseases. Additionally, berries may influence signaling pathways critical to neurotransmission, cell survival, inflammation regulation, and neuroplasticity. The abundance of phytochemicals in berries is believed to contribute to these potentially neuroprotective effects. This review aimed to explore the potential benefits of berries as a source of natural neuroprotective agents for age-related neurological disorders.

Development and validation of a predictive model for the risk of sarcopenia in the older adults in China

BackgroundSarcopenia is a progressive age-related disease that can cause a range of adverse health outcomes in older adults, and older adults with severe sarcopenia are also at increased short-term mortality risk. The aim of this study was to construct and validate a risk prediction model for sarcopenia in Chinese older adults.MethodsThis study used data from the 2015 China Health and Retirement Longitudinal Study (CHARLS), a high-quality micro-level data representative of households and individuals aged 45 years and older adults in China. The study analyzed 65 indicators, including sociodemographic indicators, health-related indicators, and biochemical indicators.Results3454 older adults enrolled in the CHARLS database in 2015 were included in the final analysis. A total of 997 (28.8%) had phenotypes of sarcopenia. Multivariate logistic regression analysis showed that sex, Body Mass Index (BMI), Mean Systolic Blood Pressure (MSBP), Mean Diastolic Blood Pressure (MDBP) and pain were predictive factors for sarcopenia in older adults. These factors were used to construct a nomogram model, which showed good consistency and accuracy. The AUC value of the prediction model in the training set was 0.77 (95% CI = 0.75–0.79); the AUC value in the validation set was 0.76 (95% CI = 0.73–0.79). Hosmer–Lemeshow test values were P = 0.5041 and P = 0.2668 (both P > 0.05). Calibration curves showed significant agreement between the nomogram model and actual observations. ROC and DCA showed that the nomograms had good predictive properties.ConclusionsThe constructed sarcopenia risk prediction model, incorporating factors such as sex, BMI, MSBP, MDBP, and pain, demonstrates promising predictive capabilities. This model offers valuable insights for clinical practitioners, aiding in early screening and targeted interventions for sarcopenia in Chinese older adults.

Aging clocks based on accumulating stochastic variation.

Aging clocks have provided one of the most important recent breakthroughs in the biology of aging, and may provide indicators for the effectiveness of interventions in the aging process and preventive treatments for age-related diseases. The reproducibility of accurate aging clocks has reinvigorated the debate on whether a programmed process underlies aging. Here we show that accumulating stochastic variation in purely simulated data is sufficient to build aging clocks, and that first-generation and second-generation aging clocks are compatible with the accumulation of stochastic variation in DNA methylation or transcriptomic data. We find that accumulating stochastic variation is sufficient to predict chronological and biological age, indicated by significant prediction differences in smoking, calorie restriction, heterochronic parabiosis and partial reprogramming. Although our simulations may not explicitly rule out a programmed aging process, our results suggest that stochastically accumulating changes in any set of data that have a ground state at age zero are sufficient for generating aging clocks.

A State-of-the-Art Review on the Role of Cognitive and Motor Reserve on Quality of Life: A Focus on Cardiovascular Patients in a Lifespan Perspective

Cardiovascular diseases (CVDs) reflect a huge and diversified condition that influences patient quality of life (QoL) both in the physical and mental aspects, especially in older adults who often present comorbidities and may be affected by cognitive decline. The concept of cognitive reserve (CR), which is built through life course experiences, has widely been considered a protective factor against cognitive decline, while the results of QoL in the field of CVDs are still controversial. In particular, there is a lack of evidence that explicitly explores the effects of CR on the QoL in CVD cases since studies have considered only single CR proxies (e.g., education) or specific cardiovascular conditions. Moreover, none of them have considered the motor reserve (MR), another recent concept that considers the amount of physical activity carried out during a lifespan. Its potential role in preventing age-related diseases has been observed, but more clarification is needed given the importance of the physical component in CVDs. The present state-of-the-art review aims to (i) examine how the literature conceives CR and its proxies in CVDs relating to QoL and (ii) integrate the concept of MR in this framework. Implications for clinical practice will also be discussed.

Bioavailability of Lutein from Marigold Flowers (Free vs. Ester Forms): A Randomised Cross-Over Study to Assess Serum Response and Visual Contrast Threshold in Adults

Lutein (Lut) and zeaxanthin (Zeax) are found in the blood and are deposited in the retina (macular pigment). Both are found in the diet in free form and esterified with fatty acids. A high intake and/or status is associated with a lower risk of chronic diseases, especially eye diseases. There is a large global demand for Lut in the dietary supplement market, with marigold flowers being the main source, mainly as lutein esters. As the bioavailability of Lut from free or ester forms is controversial, our aim was to assess the bioavailability of Lut (free vs. ester) and visual contrast threshold (CT). Twenty-four healthy subjects (twelve women, twelve men), aged 20–35 and 50–65 years, were enrolled in a cross-sectional study to consume 6 mg lutein/day from marigold extract (free vs. ester) for two months. Blood samples were taken at baseline and after 15, 40, and 60 days in each period. Serum Lut and Zeax were analysed using HPLC, and dietary intake was determined with a 7-day food record at the beginning of each period. CT, with and without glare, was at 0 and 60 days at three levels of visual angle. Lut + Zeax intake at baseline was 1.9 mg/day, and serum lutein was 0.36 µmol/L. Serum lutein increased 2.4-fold on day 15 (up to 0.81 and 0.90 µmol/L with free and ester lutein, respectively) and was maintained until the end of the study. Serum Zeax increased 1.7-fold. There were no differences in serum Lut responses to free or ester lutein at any time point. CT responses to lutein supplementation (free vs. ester) were not different at any time point. CT correlated with Lut under glare conditions, and better correlations were obtained at low frequencies in the whole group due to the older group. The highest correlations occurred between CT at high frequency and with glare with serum Lut and Lut + Zeax. Only in the older group were inverse correlations found at baseline at a high frequency with L + Z and with Lut/cholesterol and at a low frequency with Lut/cholesterol. In conclusion, daily supplementation with Lut for 15 days significantly increases serum Lut in normolipemic adults to levels associated with a reduced risk of age-related eye disease regardless of the chemical form of lutein supplied. Longer supplementation, up to two months, does not significantly alter the concentration achieved but may contribute to an increase in macular pigment (a long-term marker of lutein status) and thus improve the effect on visual outcomes.

The Vital Role of Melatonin and Its Metabolites in the Neuroprotection and Retardation of Brain Aging

While primarily produced in the pineal gland, melatonin’s influence goes beyond its well-known role in regulating sleep, nighttime metabolism, and circadian rhythms, in the field of chronobiology. A plethora of new data demonstrates melatonin to be a very powerful molecule, being a potent ROS/RNS scavenger with anti-inflammatory, immunoregulatory, and oncostatic properties. Melatonin and its metabolites exert multiple beneficial effects in cutaneous and systemic aging. This review is focused on the neuroprotective role of melatonin during aging. Melatonin has an anti-aging capacity, retarding the rate of healthy brain aging and the development of age-related neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis, amyotrophic lateral sclerosis, etc. Melatonin, as well as its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), can reduce oxidative brain damage by shielding mitochondria from dysfunction during the aging process. Melatonin could also be implicated in the treatment of neurodegenerative conditions, by modifying their characteristic low-grade neuroinflammation. It can either prevent the initiation of inflammatory responses or attenuate the ongoing inflammation. Drawing on the current knowledge, this review discusses the potential benefits of melatonin supplementation in preventing and managing cognitive impairment and neurodegenerative diseases.

Safety and efficacy of autologous adipose tissue-derived stem cell transplantation in aging-related low-grade inflammation patients: a single-group, open-label, phase I clinical trial

BackgroundInflamm-aging is associated with the rate of aging and is significantly related to diseases such as Alzheimer’s disease, Parkinson’s disease, atherosclerosis, heart disease, and age-related degenerative diseases such as type II diabetes and osteoporosis. This study aims to evaluate the safety and efficiency of autologous adipose tissue-derived mesenchymal stem cell (AD-MSC) transplantation in aging-related low-grade inflammation patients.MethodsThis study is a single-group, open-label, phase I clinical trial in which patients treated with 2 infusions (100 million cells i.v) of autologous AD-MSCs were initially evaluated in 12 inflamm-aging patients who concurrently had highly proinflammatory cytokines and 2 of the following 3 diseases: diabetes, dyslipidemia, and obesity. The treatment effects were evaluated based on plasma cytokines.ResultsDuring the study’s follow-up period, no adverse effects were observed in AD-MSC injection patients. Compared to baseline (D-44), the inflammatory cytokines IL-1α, IL-1β, IL-8, IL-6, and TNF-α were significantly reduced after 180 days (D180) of MSC infusion. IL-4/IL-10 at 90 days (D90) and IL-2/IL-10 at D180 increased, reversing the imbalance between proinflammatory and inflammatory ratios in the patients.ConclusionAD-MSCs represent a potential intervention to prevent age-related inflammation in patients.Trial registrationClinicalTrials.gov number is NCT05827757, first registered on 13th Oct 2020

Black Chokeberry (Aronia melanocarpa) Juice Supplementation Improves Oxidative Stress and Aging Markers in Testis of Aged Rats

Spermatogenesis is a process that continues until the end of an individual’s life, although with reduced activity with advancing age. Inflammation, oxidation, and apoptosis are events considered as predictors of pathogenesis and the development of age-related diseases observed in aged testes. The use of natural compounds with antioxidant and anti-inflammatory properties has a beneficial effect on the inflammatory and oxidative status of the aged testis. The aim of this study was to determine the effect of supplementation with antioxidant-rich black chokeberry (Aronia melanocarpa) juice on several markers of oxidative stress and aging in rat testis. In total, 24 male Wistar rats were divided into three experimental groups: young controls aged 2 months, old controls aged 27 months, and 27-month-old rats supplemented with black chokeberry juice at a dose of 10 mL/kg for 3 months. A. melanocarpa juice supplementation led to reduced oxidative stress, manifested by increased immunoexpression of nNOS, eNOS, and MAS1 in the seminiferous tubules and in the Leydig cells. The morphometrically determined tubule structure data showed no significant differences between the three groups. However, the intensity of the immunoreaction for TRK-C and NT3 in Leydig cells was demonstrably higher in the supplemented old animals compared with the old controls. There was a significantly higher number of blood vessels around the seminiferous tubules in the supplemented animals compared to the old controls. These data indicate that supplementation with A. melanocarpa juice slows down aging processes in the testis and preserves the functional activity of Leydig cells.