Current aging science最新文献

Background: In colorectal cancer, the investigation of cancer pathogenesis and the determination of the relevant gene and gene pathways is particularly important to provide a basis for treatment-oriented studies. miRNAs which affect gene regulation in the molecular pathogenesis of cancer, have an active role in carcinogenesis. In the literature, miRNA expression levels have been associated with metastasis and prognosis in different cancers.

Objective: In our study, expression profiling of miRNAs involved in oncogenic and apoptotic pathways in patients with locally advanced colorectal cancer receiving neoadjuvant therapy was performed.

Methods: miRNAs were isolated from three different FFPE tissue samples taken at different times of the same patient (tumor tissue taken at the time of diagnosis, normal tissue samples, and after neoadjuvant therapy). The expression analysis of 84 miRNAs determined by PCR array (Fluidigm, USA) and mediated meta-analysis was performed comparatively to each study and non-cancerous control group. Evaluations were performed with ΔΔCT calculations.

Results: As a result of the miRNA PCR array study, in addition to differences were observed in miRNA expression between control and study groups. The potential biomarkers which were hsamiR- 215-5p, hsa-miR-9-59, hsa-miR-193a-5p, hsa-miR-206, hsa-miR-1, hsa-miR-96-5p have been detected for possible treatment resistance, prognosis and predispositions to cancers.

Conclusion: In patients with colorectal cancer, miRNA expression in the tumoral regions before and after neoadjuvant therapy has represented a variable pattern. It has been shown that miRNA studies can be used to predict the clinical course and response to treatment with differences in expression levels. It has been concluded that specific miRNAs may be candidate biomarkers for colorectal cancer.

Background: It is plausible that depression symptoms and disrupting sleep quality were differently affected according to the rigidity of social distancing during the COVID-19 outbreak.

Objective: To describe and compare depression symptoms and sleep quality amongst older Brazilian and Chinese women who were submitted to different social distancing measures (less rigid (Brazil) versus more rigid (China)).

Methods: This observational cross-sectional study assessed urban older women who underwent home confinement with less (Brazil; n=1015) or more (China; n=644) rigidity. Socio-demographic correlates, general health information, depression symptoms [Geriatric Depression Scale (GDS- 15)], and sleep quality [Pittsburgh Sleep Quality Index (PSQI)] were assessed through interviews.

Results: 1659 older women (66.74 ± 5.48 years old; 38.8% Chinese; 61.2% Brazilian) were included for analysis. 22% of Brazilians and 19.6% of Chinese women presented depression symptoms. The frequency of bad sleepers was 56.4% and 37.7% amongst Brazilian and Chinese older women, respectively. After adjusting for socio-demographic variables, general health status, and PSQI global score, Chinese women had a significantly higher score of depression symptoms (3.88 ± 0.13) compared to the Brazilians (3.26 ± 0.10; p < 0.001).

Conclusion: The frequency of poor sleep quality was very high regardless of the country. After adjusting for confounders and sleep quality, older Chinese women had a significantly superior score of depression symptoms exacerbating psychological distress by confinement rigidness.

Background: Neuropsychiatric symptoms (NPS) are highly prevalent among individuals with major neurocognitive disorders (MNCD).

Objective: Here, we characterized blood biomarkers (metabolic, inflammatory, neurotrophic profiles and total antioxidant), body composition, physical fitness and quality of life (QoL) in individuals with MNCD according to NPS.

Methods: The sample comprised 34 older adults (71.4% women; 74.06±6.03 yrs, with MNCD diagnosis) categorized according to 50th percentile [Low (≤12) or High (≥13)] for NPS (Neuropsychiatric Inventory Questionnaire). Sociodemographic, clinical data, body composition, anthropometric, cognitive assessment (ADAS-Cog), physical fitness (Senior Fitness Test), QoL (QoL-Alzheimer's Disease scale) were evaluated, and blood samples were collected for biochemical analysis.

Results: Low compared to high NPS group showed higher levels of IL-6, IGF-1and neurotrophic zscore (composite of IGF-1, VEGF-1, BDNF). Additionally, low compared to high NPS group have higher QoL, aerobic fitness and upper body and lower body strength.

Conclusion: The severity of NPS seems to be related to modified neurotrophic and inflammatory outcomes, lower physical fitness, and poor QoL. Strategies to counteract NPS development may preserve the physical and mental health of individuals with MNCD.

Background: 'Rapid balance reaction' or 'perturbation' training is an emerging paradigm in elderly back pain rehabilitation due to its connection to postural stability.

Objective: This study aimed to inform the feasibility and practicality of perturbation-based balance training (PBT) using a stratification approach and to determine the effectiveness of land versus water-based PBT in elderly individuals with chronic low back pain (CLBP).

Methods: Elderly CLBP participants (n=24) received exercise interventions as per treatmentbased classification (TBC) and were randomly allotted into water-based perturbation exercises (WBPE, Mean age=63.0±2.6years, n=12) and land-based perturbation exercise group (LBPE, 62.3±2.6 years, n=12). Pain intensity, disability, scores of fear-avoidance beliefs, fall efficacy, and rate of perceived exertion (RPE) were assessed before and at the end of 6 weeks.

Results: WBPE group reported a significant reduction in pain score (median difference(MD)):2, p<0.03), fear avoidance behaviour for work (MD:9, p<0.01) and fear avoidance behaviour for physical activity (MD:10, p< 0.05), improved straight leg raise right (SLR) (MD:37.5°, p<0.05), and improved modified fall efficacy scores (MFES, MD:25, p<0.05) compared to the LBPE group at post-intervention. Within-group analysis in both groups revealed significant improvement in clinical outcomes except for fear-avoidance beliefs related to physical activity in the LBPE group. Subgroup analysis revealed that the high BMI elderly CLBP group of LBPE had significant improvements similar to the WBPE group except for scores of FABQ physical activity scores and SLR.

Conclusion: Possible key factors for future research are discussed in the realms of perturbation exercise in the elderly with CLBP.

Background: Loss of functional capacity negatively impacts the quality of life in older adults.

Objective: This single-site randomized controlled study examined whether short- (one week) and long-term (three months) blackcurrant supplementations combined with habitual physical activity would improve functional capacity and quality of life in previously sedentary older women.

Methods: Thirty sedentary, healthy older women were randomly assigned to receive blackcurrant supplementation (400 mg of blackcurrant extract) (Polyphenol group, n=15; 74.2±10.0 years) or no supplementation (capsules of 400 mg of corn flour) (Placebo group, n=15; 72.8±8.7 years). Each group consumed two capsules daily for one week and three months, with a washout period of one week between the two phases. The polyphenol group was required to increase habitual activity levels. Participants underwent a functional capacity assessment consisting of a sixminute walk, sit-to-stand test, Berg balance scale measurement and quality of life evaluation with the Scale of Life Satisfaction Index (LSI) at the start, after one week, and after three months of supplementation.

Results: Walking distance and time to sit-to-stand improved by 2.5% (p=0.005) and 7.5% (p=0.005), respectively, after one week in the polyphenol group. After 3 months, walking distance in the six-minute walk test increased by 12.3% (p=0.001) while the time to sit-to-stand decreased by 16% (p=0.002) in the polyphenol compared to placebo group, respectively. No differences in Berg balance scale were observed. Quality of life, indexed by LSI, improved by 39% (p=0.001) in the polyphenol compared to the placebo group.

Conclusion: Blackcurrant supplementation, combined with habitual activity, may enhance functional capacity and quality of life in older women, offering a potential strategy to maintain independence. However, future studies should address longer durations to validate these findings.

Background: Duchene Muscular Disorder (DMD) is a severe X-linked recessive neuromuscular disease. Previous reports predicted that one-third of cases with a fatal X-linked recessive disease will be caused by a novel mutation, and the mutation rate for DMD seems to be higher in males.

Objective: A novel mutation in the DMD gene DMD (NM_004006.3):c.92A>G (p.Lys31Arg) is suggested for males because of their heterozygous mothers carrying the mutant alleles.

Method: Whole Exome Sequencing (WES) was done for a 25-year-old female followed by the screening of the novel mutation in her parents and her brother by the Sanger sequencing technique. Some in silico analyses were run to find the putative alterations in wild-type and mutant structures by PolyPhen-2 and Mupro. Notably, SWISS-MODEL was performed to build a reliable model for the mutant allele based on the PDB ID: 1DXX structure. Also, superimposition was done by PyMol.

Results: WES analysis revealed three novel mutations including DLD (exon13:c.G1382A:p. G461E), ABCA3 (exon12:c.G1404C:p.W468C), and DMD (exon2:c.A92G:p.K31R) in the case. Focusing on DMD mutation, Sanger sequencing of the patient's parents and brother indicated no mutant allele in her mother and brother but a mutant allele in her father as a hemizygous pattern. In silico analyses showed no considerable change regarding pathogenic impact.

Conclusion: In conclusion, our findings revealed no pathogenic effect of the new mutation (K31R) of the DMD gene in an Iranian 25-year-old woman. Because of the DMD importance in preclinical diagnosis, these data may shed a light on the diagnosis of this mutation in future pregnancies.

Background: Dizziness and balance disorders are directly related to aging in humans- Dizziness is one of the most important factors causing the burden of disability after the age of 65. Bearing in mind the increase in the elderly population in Iran and the world and the prevalence of dizziness in old age, early diagnosis of dizziness and determination of the factors affecting its severity facilitate its treatment and are effective in preventing its adverse consequences.

Objective: To determine the prevalence of dizziness and its related factors among older adults in Ardakan city, Yazd province, Iran, in 2022.

Methods: This cross-sectional study was conducted in four comprehensive health centers of Ardakan city with the participation of 260 elderly people aged ≥60 years, who were randomly included in the study. Data were collected using a series of questionnaires which were completed by interviewing the participants. The variables of this study included demographic information, information related to the dizziness status, diseases, medications, use of mobility aids, physical activity level, fear of falling, quality of life and depression.

Results: The prevalence of dizziness among older adults of Ardakan city was 48.5%. In terms of the severity of dizziness, 38.8% had substantial dizziness, and 9.6% had mild dizziness. Dizziness was significantly related to physical activity (p<0.05), fear of falling (p <0.01), depression (p <0.05), history of falling (p <0.01), use of mobility aids (p <0.01), age (p<0.01), education level (p<0.01), gender (p <0.05) and diseases such as high blood pressure (p<0.05), hypothyroidism (p <0.01) and ear diseases(p <0.01). Also, elderly people with dizziness used significantly more medications such as sedatives (p<0.01), antihypertensive drugs (p <0.05) and cytotoxic drugs (p <0.01).

Conclusion: About half of the older adults experience dizziness, and this problem is associated with depression, fear of falling, history of falling, low physical activity, age, female gender, ear diseases, high blood pressure, and hypothyroidism. In addition, the use of medications such as anti- hypertensives, sedatives and cytotoxic drugs is related to dizziness. Families with elderly people, doctors and healthcare workers need to be educated and pay more attention to the above.

Our group at Yuvan Research has conducted several experiments in recent years that have demonstrated the reversibility of aging through the use of a young plasma fraction, following a historical line of research that began with heterochronic parabiosis. However, a one-of-a-kind discovery, in the form of anecdotal evidence, has recently clarified many doubts about the nature of aging and rejuvenation, and the conclusions that can be drawn from this discovery allow us to form a relatively clear picture of the mechanics of the aging and rejuvenation processes.

Background: Excessive manganese exposure can lead to neurotoxicity with detrimental effects on the brain. Neuroinflammatory responses and redox regulation play pivotal roles in this process. Exploring the impact of hyperoside in a Wistar rat model offers insights into potential neuroprotective strategies against manganese-induced neurotoxicity.

Objective: The study investigated the neuroprotective efficacy of hyperoside isolated from the ethanol leaf extract of Gongronema latifolium (HELEGL), in the brain tissue of Wistar rats following 15 consecutive days of exposure to 30 mg/L of MnCl2.

Methods: Control animals in Group 1 had access to regular drinking water, while animals in groups 2-4 were exposed to MnCl₂ in their drinking water. Groups 3 and 4 also received additional HELEGL at doses of 100 mg/kg and 200 mg/kg of body weight, respectively. In Group 5, HELEGL at a dose of 100 mg/kg of body weight was administered alone. Treatment with HELEGL commenced on day 8 via oral administration.

Results: HELEGL effectively mitigated MnCl₂-induced memory impairment, organ-body weight discrepancies, and fluid intake deficits. Exposure to MnCl₂ increased the activities or levels of various markers such as acyl peptide hydrolase, tumour necrosis factor-α, dipeptidyl peptidase IV, nitric oxide, IL-1β, prolyl oligopeptidase, caspase-3, myeloperoxidase, H₂O₂, and malondialdehyde, while it decreased the activities or levels of others, including AChE, BChE, DOPA, serotonin, epinephrine, norepinephrine, GST, GPx, CAT, SOD, GSH, and T-SH (p < 0.05). In contrast, HELEGL effectively counteracted the adverse effects of MnCl₂ by alleviating oxidative stress, inflammation, apoptosis, mitochondrial dysfunction, cognitive deficits, and bolstering the antioxidant status. Moreover, HELEGL restored the normal histoarchitecture of the brain, which had been distorted by MnCl₂.

Conclusion: In summary, HELEGL reversed the causative factors of neurodegenerative diseases induced by MnCl₂ exposure, suggesting its potential for further exploration as a prospective therapeutic agent in the management of Alzheimer's disease and related forms of dementia.