Dataset Information

Analysis of the Effects of Ninjin'yoeito on Physical Frailty in Mice.

ABSTRACT: Physical frailty is an aging-related clinical syndrome involving decreases in body weight, mobility, activity, and walking speed that occurs in individuals with sarcopenia and is accelerated by increased oxidative stress. Ninjin'yoeito, a traditional Japanese Kampo medicine, is used for treating conditions, including anemia and physical weakness. Here, we investigated whether ninjin'yoeito could improve physical frailty by controlling oxidative stress in the senescence-accelerated mouse prone 8 (SAMP8) model. First, SAMP8 mice were divided into two groups, ninjin'yoeito treated and untreated, with the former consuming a diet containing 3% ninjin'yoeito from 3 months of age. At 7 months of age, body weight, motor function, locomotor activity, and mean walking speed were measured. Subsequently, mice were euthanized and measured for muscle weight, 8-hydroxy-2'-deoxyguanosine levels in muscle and brain, and cleaved caspase-3 expression in brain. The results showed reductions in weight, locomotor function, locomotion, and average walking speed in the untreated group, which were significantly improved by ninjin'yoeito. Furthermore, 8-hydroxy-2'-deoxyguanosine levels were reduced in muscle and brain from ninjin'yoeito-treated mice, compared with the levels in untreated mice; cleaved caspase-3 expression was similarly reduced in brain from the treated mice, indicating reduced apoptosis. Our findings suggest that ninjin'yoeito inhibits sarcopenia-based physical frailty through its antioxidant effects.

SUBMITTER: Otsuka S

PROVIDER: S-EPMC9569708 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Analysis of the Effects of Ninjin'yoeito on Physical Frailty in Mice.

Otsuka Shotaro S Fukumaru Keita K Tani Akira A Takada Seiya S Kikuchi Kiyoshi K Norimatsu Kosuke K Matsuzaki Ryoma R Matsuoka Teruki T Sakakima Harutoshi H Omiya Yuji Y Mizuno Keita K Matsubara Yosuke Y Maruyama Ikuro I

International journal of molecular sciences 20220923 19

Physical frailty is an aging-related clinical syndrome involving decreases in body weight, mobility, activity, and walking speed that occurs in individuals with sarcopenia and is accelerated by increased oxidative stress. Ninjin'yoeito, a traditional Japanese Kampo medicine, is used for treating conditions, including anemia and physical weakness. Here, we investigated whether ninjin'yoeito could improve physical frailty by controlling oxidative stress in the senescence-accelerated mouse prone 8 ...[more]

PMID: 36232484

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Project description:With the recent aging of society, the prevention of frailty has become an important issue because people desire both a long and healthy lifespan. Klotho-hypomorphic (kl/kl) mice are known to show phenotypes of premature aging. Ninjin'yoeito (NYT) is a traditional Japanese Kampo medicine used to treat patients with vulnerable constitution, fatigue or physical exhaustion caused by aging and illness. Recent studies have reported the potential efficacy of NYT against frailty. We therefore evaluated the effect of NYT on the gait function, activity, the histopathological status of organs and survival using kl/kl mice as a model of aging-related frailty. Two sets of 28-day-old male kl/kl mice were assigned to the vehicle (non-treated; NT), 3% or 5% NYT dietary groups. One set of groups (NT, n = 18; 3% NYT, n = 11; 5% NYT, n = 11) was subjected to the analysis of free walking, rotarod, and spontaneous activity tests at approximately 58 days old. Thereafter, we measured triceps surae muscles weight and myofiber cross-sectional area (CSA), and quantified its telomere content. In addition, we evaluated bone strength and performed histopathological examinations of organs. Survival was measured in the second set of groups (NT, 3% NYT and 5% NYT group, n = 8 each). In the walking test, several indicators such as gait velocity were improved in the NYT 3% group. Similar results were obtained for the latency to fall in the rotarod test and spontaneous motor activity. Triceps muscle mass, CSA and its telomere content were significantly improved in the NYT 3% group. Bone density, pulmonary alveolus destruction and testicular atrophy were also significantly improved in the NYT 3% group. Survival rate and body weight were both significantly improved in the NYT3% group compared with those in the NT group. Continuous administration of NYT from the early stage of aging improved not only gait performance, but also the survival in the aging-related frailty model. This effect may be associated with the improvements in aging-related organ changes such as muscle atrophy. Intervention with NYT against the progression of frailty may contribute to a longer, healthier life span among the elderly individuals.

Project description:Introduction In geriatric medicine, there is currently significant attention on frailty, a condition commonly associated with aging and characterized by muscle weakness and other age-related changes. Within the fields of urology and gynecology, conditions such as overactive bladder (OAB) and genitourinary syndrome of menopause (GSM) have been identified as crucial concerns due to their negative impact on the quality of life of elderly individuals. In this study, we investigated the potential of Ninjin'yoeito (NYT), a traditional Chinese herbal medicine, as a viable treatment option for frailty. Additionally, we hypothesized that NYT may also contribute to the improvement of symptoms associated with OAB and GSM, and potentially help in reducing the dosage of OAB medications. Methods In this retrospective cohort study conducted from November 2016 to November 2022, we created a website describing the relationship between frailty and genitourinary symptoms in frail patients aged ≥ 65 years with GSM who underwent pelvic floor muscle training. The patients were divided into two propensity score-matched groups: NYT group (received NYT for one year) and no-NYT group (did not receive NYT), based on their wishes. The fatigue, resistance, ambulation, illnesses, and loss of weight (FRAIL) scale was used to assess frailty status. Urinary symptoms were evaluated using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Overactive Bladder Symptom Score (OABSS). Genital symptoms were investigated using the vaginal health index score and vulvodynia swab test. The value of each score was obtained before (T0) and 12 months after (T12) treatment, and the difference (ΔT0/T12) was calculated. Results During the study period, 985 outpatients visited our clinic, of whom 725 were considered frail/pre-frail; 402 women with frailty/pre-frailty (mean age 77.5 ± 6.49 years) were included, with a median follow-up of 14.5 months. The NYT and no-NYT groups had 220 and 182 patients, respectively. After propensity score matching, each group had 159 patients. ΔT0/T12FRAIL scale score was significantly higher in the NYT group (0.13 ± 0.37) than in the no-NYT (0.01 ± 0.10) group (p=0.001.) However, urinary symptoms improved in the NYT group more than in the no-NYT in terms of the following parameters: ΔT0/T12OABSS (NYT: 0.89 ± 1.65; no-NYTl: 0.36 ± 1.14, p=0.001) and ΔT0/T12ICIQ-SF score (NYT: 1.51 ± 1.75; no-NYT: 0.42 ± 1.18, p<0.001). Genital symptoms were better in the NYT group in terms of ΔT0/T12VHIS (NYT: 0.58 ±1.08; no-NYT: 0.21 ±0.65, p<0.001). The vulvodynia swab test showed improvements in left para-hymen evoked pain in both groups. In the NYT group, 5% of the patients underwent antimuscarinic drug dose reduction for overactive bladder treatment. NYT use was not associated with significant side effects, and only 0.6% of patients reported drug allergies. Conclusion NYT improved activity levels in frail/pre-frail patients. Moreover, NYT use improved various genitourinary symptoms experienced by patients with frailty/pre-frailty. Treatment with NYT may reduce the dose of overactive bladder medications. The anticholinergic load-reducing effect of NYT may help solve the problem of polypharmacy.

Project description:IntroductionThe prevalence of frailty is increasing worldwide, emphasizing the importance of prioritizing healthy ageing. To address this, cost-effective and minimally supervised interventions are being sought. This study aimed to assess the impact of an educational program on frailty status, physical function, physical activity, sleep patterns, and nutritional status in community-dwelling older adults with at least 1 Fried's frailty criteria.MethodsA 6-month multicentre randomized controlled trial was conducted from March 2022 to February 2023 in 14 health centres located in Cadiz and Malaga, Spain. The educational intervention consisted of 4 group sessions and 6 follow-up phone calls spread over 6 months. The program focused on educating participants about frailty and its impact on health, providing guidelines for physical activity, healthy dietary habits, cognitive training, psychological well-being and social activities. A total of 163 participants, divided into control (n = 80) and educational groups (n = 83) were assessed before and after the intervention.ResultsThe results showed a significant group-time interaction in the physical function evaluated with a large effect on Short Physical Performance Battery score (η2p = 0.179, -0.1 [-1.2-1.0] points for control group vs. 1.0 [0.0-3.0] points for educational group, p < 0.001), and an effect on the 4-meter gait test ((η2p = 0.122, 0.5 [0.1-0.0] s for control group vs. -0.4 [-0.5- -0.3] s for educational group, p < 0.001), and the 5-repetition sit-to-stand test (η2p = 0.136, 1.0 [0.0-1.2] s for control group vs. -4.3 [-7.0- -2.3] for educational group, p < 0.001). Additionally, the use of accelerometers to assess physical activity, inactivity, and sleep patterns revealed a significant small effect in the number of awakenings at night ((η2p = 0.040, 1.1 [-0.5-3.4] awakenings for control group vs. 0.0 [-2.2-0.0] awakenings for educational group, p = 0.009). The findings also highlighted a significant medium effect regarding malnutrition risk, which was assessed using the Mini-Nutritional Assessment score (η2p = 0.088, -0.7 [-2.3-1.5] points for control group vs. 1.5 [-0.5-3.0] points for educational group, p < 0.001).DiscussionThus, the 6-month educational program effectively improved physical function, sleep patterns, and nutritional status compared to usual healthcare attendance in community-dwelling older adults with frailty or pre-frailty. These findings underscore the potential of minimally supervised interventions in promoting a healthy lifestyle in this vulnerable population.

Project description:BackgroundFew studies have made longitudinal comparisons between frailty phenotype (FP) and frailty index (FI) changes. We aimed to investigate frailty status changes defined by FP and FI concurrently, and to compare the associated factors and incident disability among different combination of FI and FP trajectory groups.MethodsData on respondents aged over 50 who completed the 1999, 2003 and 2007 Taiwan Longitudinal Study on Aging (TLSA) surveys (n = 2807) were excerpted. Changes of FI, FP and major time-dependent variables were constructed by group-based trajectory modeling. Logistic regression was used to investigate the associated factors and relationships with incident disability among different frailty trajectories.ResultsWe identified four FP trajectories - stably robust, worsened frailty, improved frailty, and stably frail and three FI trajectories - stable FI, moderate increase FI and rapid increase FI. Lower self-rated health, mobility impairment, and depressed mood were associated with unfavorable FP and FI changes (all p < 0.001). Regardless of FP trajectory groups, the moderate and rapid increase FI group had significantly more comorbidities than the stable FI group, and more visual, hearing, oral intake impairment, more difficulty in meeting living expenses, and poorer cognitive function in ≥65-year-olds (all p < 0.05). In addition, the worsened frailty, improved frailty, and stably frail groups had ORs for incident disability of 10.5, 3.0, and 13.4, respectively, compared with the stably robust group (all p < 0.01); the moderate and rapid increase FI groups had 8.4-fold and 77.5-fold higher risk than the stable FI group (both p < 0.001). When combining FI and FP trajectories, risk increased with FI trajectory steepness, independent of FP change (all p < 0.01 in rapid increase FI vs stable FI).ConclusionsFour FP trajectories (stably robust, worsened frailty, improved frailty, and stably frail) and three FI trajectories (stable FI, moderate increase FI and rapid increase FI) were identified. Lower self-rated health, mobility impairment, and depressed mood were associated with both unfavorable FP and FI trajectories. Nevertheless, even for individuals in stably robust or improved frailty FP groups, moderate or rapid increase in FI, either due to comorbidities, sensory impairment, cognitive deficits, or financial challenges, may still increase the risk of incident disability.

Dataset Information

Analysis of the Effects of Ninjin'yoeito on Physical Frailty in Mice.

Publications

Analysis of the Effects of Ninjin'yoeito on Physical Frailty in Mice.

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