Current Aging Science - Volume 14, Issue 2, 2021

New models in which aging-related neurodegeneration more closely resembling the combination of pathologies that develop in aging humans, are needed. The fish Nothobranchius, which naturally develops such pathologies over the course of its short lifespan, is one such model. This review compares the lifespans and pathologies of different Nothobranchius strains to those of current vertebrate models of aging. Furthermore, existing data pertaining to neurodegeneration in these fish is discussed in the context of their reported neuropathologies, along with open questions related to mammalian chronopathologies. Specifically, the evidence for a Parkinson’s disease-like pathology is discussed. Neurogenesis and age-related changes therein are discussed in the context of siRNA and neurodegeneration. We also discuss changes in the expression of neuropeptide Y in relation to the brain-gut axis and how these change with age. Age-related behavioral changes are discussed, along with the assays used in their evaluation. Genetic discoveries are outlined and discussed with a view on DJ-1/NRF2 signaling in N. furzeri, and insights gained from comparative genomics and siRNA studies. Finally, research focus areas are highlighted, and a case is made for the utility of these fish in the study of aging-related neurodegeneration, and to screen for environmental risk factors of aging-related neuropathology.

Sarcopenia is a commonly prevalent geriatric condition mainly characterized by progressive loss of the skeletal muscle mass that results in noticeably reduced muscle strength and quality. Most of the geriatric population above 60 years of age are overweight, leading to the accumulation of fat in the muscles resulting in abated muscle function. The increased loss of muscle mass is associated with high rates of disability, poor motility, frailty and mortality. The excessive degeneration of muscles is now also being observed in middle-aged people. Therefore, geriatrics has recently started shifting towards the identification of early stages of the disability in order to expand the life span of the patient and reduce physical dependence. Recent findings have indicated that patients with increased physical activity are also affected by sarcopenia, therefore indicating the role of nutritional supplements to enhance muscle health which in turn helps to counteract sarcopenia. Various interventions with physical training have not provided substantial improvements to this disorder, thereby highlighting the crucial role of nutritional supplementation in enhancing muscle mass and strength. Nutritional supplementation has not only been shown to enhance the positive effects of physical interventions but also have a profound impact on the gut microbiome that has come forward as a key regulator of muscle mass and function. This brief review throws light upon the efficiency of nutrients and nutraceutical supplementation by highlighting their ancillary effects in physical interventions as well as improving the gut microbiome status in sarcopenic adults, thereby giving rise to a multimodal intervention for the treatment of sarcopenia.

Introduction: One of the consequences of aging is the prevalence of chronic and age-related diseases, such as dementia. Caring for patients with dementia has a negative impact on the caregiver's well-being. This study aimed to examine the impact of cyberspace-based education on the well-being of caregivers of demented elderly people. Methods: This experimental study was done on a sample of 86 caregivers of the elderly with dementia in 2018. The study sample was selected from the memory clinic of Taleghani Hospital and randomly assigned into groups (intervention n = 43, control n = 43 groups). The well-being was measured using the World Health Organization - Five Well-Being Index (WHO-5) before and two months after the intervention. The cyberspace-based educational intervention was conducted for one month. The SPSS software version 23 was employed in data analysis. Results: The mean age of the caregivers in the intervention and control groups were M = 51.95, SD = 10.90 and M = 51.36, SD = 15.12 respectively. No significant difference was found between the two groups in terms of age, gender, and level of education. The results of the analysis showed that while the well-being of the intervention group was significantly increased (t (38) = -11.38, P<0.001), the well-being in the control group was significantly reduced (t(36) =4.71, P<0.001). Conclusion: The findings showed that cyberspace-based education could improve the well-being of caregivers of the elderly with dementia.

Background: Aging is associated with most neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Determination of peripheral blood biomarkers represents a low invasive approach for tracking early changes in body metabolism during aging. Objective: This study addresses a cross-sectional analysis to identify changes in lipid, minerals, and antioxidant capacity as potential biomarkers to the onset of neurodegenerative diseases during aging. Methods: A retrospective analysis was performed to determine age-related biomarkers from a clinical sample database. Next, one hundred volunteers between 20-59 (adult) and over 60 years (elderly) were selected for the motor and cognitive tests according to Unified Parkinson's Disease Rating Scale (UPDRS) and Mini-Mental State Examination (MMSE), respectively. Peripheral blood samples were also collected to determine circulating lipids, minerals, and antioxidant capacity. Results: Lipid profile revealed an increase in triglycerides, total, and VLDL Cholesterol. Among the elderlies, HDL was lower than the adult group, particularly in volunteers with severe cognitive decline. Minerals involved in antioxidant defense such as iron, selenium, and manganese were lower in elderly people compared to adults. Catalase activity was also reduced among elderlies with mild cognitive impairment. Conclusion: Here, we show changes in key serum biomarkers correlate with aging and clinical cognitive decline among elderly people. These findings may contribute to the understanding of how biomarkers can be useful for early diagnosis and treatment of aging-related diseases.

Background: The antidepressant Mianserin has been shown to extend the lifespan of Caenorhabditis elegan (C. elegan), a well-established model organism used in ageing research. The extension of lifespan in C. elegan was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegan elegan in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegan on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegan abolishes the lifespan-extension effects of mianserin.

Aims: The aim of the experiments was to find out the factors on which age-related sensitivity to the occurrence of BPH depends. Methods: 45 Male Wistar rats aged 3 and 24 months were used. In each age group, there were intact rats and animals with induced BPH (by surgical castration + testosterone injections, 25 mg/kg x 7). On the 36th day of the experiment, blood was taken from rats to determine serum testosterone, cholesterol, triglycerides and glucose; then, the animals were autopsied, their prostates were weighed, and their morphology was studied. Results: Young mature intact rats had much higher testosterone levels (6.2±0.93 nmol/l) than old intact (3.8±0.55 nmol/l), while the ratio of prostate weight was inverse. The weight of the prostate and prostatic index in old rats with induced BPH was significantly higher not only in comparison with the old intact rats but also with young animals after BPH induction. Morphologically, the inflammatory foci were determined not only in the prostates of old rats, which induced BPH, but also in intact animals. Besides, in old intact rats, the foci of prostate hyperplasia were often noted. Conclusion: Our experimental model indicates the important role of non-bacterial prostatitis in the pathogenesis of BPH. No metabolic disorders in BPH induction were revealed. The sensitivity of the prostate of old rats to BPH development is increasing despite the low concentrations of testosterone in the body. Age sensitivity to BPH is probably determined by a higher expression of androgen receptors in old animals.

Background: Hyperkyphosis is one of the commonly seen disabilities in the elderly. Loss of muscle mass and function is supposed to be related to age-related hyperkyphosis. We aimed to explain the relationship between sarcopenia and hyperkyphosis in old patients in this study. Methods: 142 patients who were in the polyclinic of geriatrics of Gaziantep University Hospital were enrolled in this cross-sectional study. Hyperkyphotic patients were included in the study group, and non-hyperkyphotic patients were included in the control group by experienced staff. Their mean age was 72±6.9. Thirty-six of them were male, and 106 of them were female. The EWGSOP 2 criteria were used for the diagnosis of sarcopenia. SARC-F (sluggishness, assistance in walking, rising from a chair, climb stairs, falls) test was performed on all patients. The handgrip test was applied to patients who had a score ≥4 from SARC-F. We conducted bioimpedance analysis of the probable sarcopenic patients who were diagnosed with handgrip assessment. Four-meter gait speed test, Timed Up and Go Test (TUG) and Tinetti Test were applied to all patients to evaluate gait speed. Hyperkyphosis was evaluated with the bloc method in the Rancho Bernardo Study. Numbers of the blocks used for keeping patients in a neutral position were recorded. We defined hyperkyphosis as the state in that one or more blocks are needed to maintain the patient's neutral position on the radiology table. Results: Hyperkyphosis was positively related to lower extremity dysfunction which was assessed by 4-m-gait speed test (p=0.018) and TUG (p=0.042). A significant relationship between gait speed and hyperkyphosis was revealed when evaluated with one-way MANOVA (F [5,92] =2.588, p=0.031, Wilk's Λ=0.877, partial η2=0.123). We found a significant relationship between TUG and the number of blocks needed to restore neutral position by linear regression analyses (r² =0.059, p=0.044). We found a cut-off value of gait speed as 0.65 m/s for the presence of hyperkyphosis (sensitivity:60%, specificity:70%, CI=95%, p<0.001, AUC=0.710). Tinetti balance, gait and total test scores were also negatively related to hyperkyphosis (p=0.006; 0,027; 0.031). Conclusion: In previous studies, vertebral compression fractures, degenerative disc disease, weakness of back extensor muscles and genetic predisposition were suggested as predisposing factors for age-related kyperkyphosis. Different from these in our study, lower extremity muscle function was found to be related to age-related hyperkyphosis. More studies on this subject could be helpful. Hyperkifosis prognosis in severe sarcopenic groups might be a new research topic.

Background: Rhodiola rosea is a herb that has been used in traditional medicine for several years, and LF is a class of lipoproteins derived from the fish Trachurus sp. (LF-T), which exhibits known anti-inflammatory activity. Objective: Investigating the anti-aging effect of Rhodiola specific bioactive fractions cluster in combination with LF-T (R-L compound) in H2O2 mediated oxidative stress-induced human amnion derived epithelial cell line - FL cells as normal human cell line. Methods: FL cells were treated with H2O2 to induce cellular aging, followed by treatment of the RL compound to study its anti-aging characteristics. Based on the proliferation rate, 0.05% and 0.1% concentration of R-L compound was determined using MTT assay. Anti-aging and anti-oxidant assays, ABTS, DPPH, Hyaluronidase activity Nitric Oxide, Lipid Peroxidase, and Superoxide Dismutase were performed. qPCR for anti-aging genes and matrix metalloproteinase genes were analyzed. Results: FL cells treated with R-L compound exhibited increased proliferation rate and free-radical reduction. Decreased Hyaluronidase enzyme activity and regulation of genes such as SIRT1, KLOTHO, SERPINA 6, MMP 9, and MMP 2 expression depicted the anti-aging role of the R-L compound. Chemometric profiling of the R-L compound revealed that aromatic compounds and unsaturated fatty acids along with their derivatives, were present predominantly, which might have attributed to the potent oxidative stress impeded aging activity. Conclusion: Specific Bioactive Fractions of Rhodiola in combination with LF-T obtained from Trachurus sp. involve in the regulation of aging genes and might be a novel approach to prevent the cells from oxidative stress damage and also it might avert the aging of cells.

Background: Organismal aging has been associated with deleterious effects in different body tissues and organs, including the brain. There have been reports from ancient medicinal scripts of the beneficial effects of nuts like hazelnut in preventing aging induced-brain atrophy and memory loss. Objectives: This study examined the potential beneficial effects of a diet supplemented with two different (Italian and Turkish) cultivars of hazelnut on the brain of aged mice. Methods: Aged (24 months old) mice were randomly assigned into 7 groups of ten mice each. Mice were grouped as standard diet (SD) control, three groups of Turkish and three groups of Italian hazelnut incorporated into SD at 2, 4 and 8% respectively. Animals were fed standard or hazelnut diet for 8 weeks. On day 56, behaviours in the elevated plus maze, radial-arm maze, open field, and Y-maze paradigms were monitored and scored, following which animals were euthanized. The brains were removed, weighed and homogenized for the assessment of specific biochemical tests. Result: Results showed that hazelnut-supplemented diet was associated with significantly increased weight gain, with the Italian hazelnut being associated with greater weight gain. The hazelnut- supplemented diet also increased behavioural parameters such as horizontal locomotion and grooming, while it decreased rearing activity. Working-memory also improved significantly with both cultivars of hazelnut, while anxiety indices were reduced at lower concentrations of Italian, and higher concentrations of Turkish hazelnut. Both hazelnut varieties were associated with a reduction in acetylcholinesterase activity, superoxide dismutase activity, nitric oxide levels, caspase- 3 level, but increased dopamine level. Conclusion: Overall, hazelnut cultivars have beneficial effects on the brain in aged mice; suggesting a possible role in the prevention or management of age-related neurodegenerative changes.