Rejuvenation research最新文献

Pathogenesis of vascular dementia (VD) is still unclear, there are currently no effective prevention and treatment methods. We applied Mendelian randomization (MR) using summary statistics from large-scale GWAS of metabolites and VD to reveal the causal effect of metabolites on the VD. One set of genetics instrument was used for analysis, derived from publicly available genetic summary data. Which was 32 single-nucleotide polymorphisms robustly associated with metabolites. Inverse-variance weighted, weighted median method, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier test were used for MR analyses. Strong evidence for a positive effect of metabolites, which means N6-threonylcarbamoyladenosine (t⁶A) on VD was found in inverse-variance weighted (odds ratios [OR]: 0.667, 95% confidence interval [CI]: 0.548-0.812, p < 0.001), MR-Egger (OR: 0.647, 95% CI: 0.458-0.913, p = 0.019), and weighted median (OR: 0.650, 95% CI: 0.466-0.908, p = 0.012). The MR analysis indicated that metabolites (t⁶A) may be causally associated with a positive effect on VD.

Parishin, a natural compound, has demonstrated significant potential in mitigating age-related phenotypes and improving outcomes in age-associated diseases. Given that aging is a major risk factor for numerous chronic conditions, including pulmonary fibrosis, we investigated parishin's effects on cellular senescence and lung health. In our study, we treated mouse lung epithelial cells with parishin and observed a reduction in cellular senescence markers alongside an upregulation of sirtuin 1 (SIRT1). Building on these in vitro findings, we administered parishin to naturally aged mice. The treatment resulted in decreased pulmonary fibrosis and reduced DNA damage in lung tissue. Notably, we found that parishin treatment led to a reduction in Cluster of differentiation 38 (CD38) levels, concomitant with an increase in SIRT1 expression. These findings indicate that parishin may enhance lung function in aged mice, suggesting its potential as a therapeutic agent for treating age-related pulmonary disorders.

To observe the effects of moxibustion on T cells and T cell immunoglobulin and mucin-domain-containing molecule-3/galectin-9 (Tim-3/Gal-9) pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA. Thirty Sprague Dawley rats were randomly divided into three groups, including a control group, an RA model group, and a moxibustion group. An RA model was created through the injection of Freund's complete adjuvant. In the moxibustion group, rats were treated with moxibustion at acupoints of "Shenshu" and "Zusanli." A total of three courses of treatment were conducted. Then the thickness of foot pad was measured, joint pathological changes were observed by hematoxylin-eosin (HE) staining, the proportion of CD4⁺T and CD8⁺T in peripheral blood was detected by flow cytometry, the expression levels of Tim-3 and Gal-9 in synovium were detected by polymerase chain reaction (PCR), and the expressions of CD4⁺T and CD8⁺T in synovium were detected by immunofluorescence. HE staining showed that the synovial tissue of the control group was smooth and neatly arranged without inflammatory cell infiltration. In the model group, the joint space was narrowed, the synovial tissue had congestion and edema, and a large number of inflammatory cells infiltrated. Compared with the model group, in the moxibustion group, the joint space narrowed with synovium hyperemia and edema, and the level of inflammatory cell infiltration decreased. Flow cytometry showed that compared with the model group, CD4⁺T expression in the moxibustion group was downregulated, while CD8⁺T expression was upregulated. PCR results showed that compared with the model group, the expressions of Tim-3 and Gal-9 in the moxibustion group were upregulated. Immunofluorescence results showed that compared with the model group, CD4⁺T expression in the moxibustion group was decreased, while CD8⁺T expression was increased. The results demonstrate that moxibustion not only suppressed the expression of CD4⁺T but also promoted the expression of CD8⁺T. The anti-inflammatory effect of moxibustion may be related to the regulation of T cell expression through the Tim-3/Gal-9 signaling pathway.

Parkinson's disease (PD) is accompanied by a complex array of nonmotor and motor manifestations. The exploration of anti-inflammatory and antioxidant active ingredient as potential therapeutic interventions in PD-associated mood alterations has gained significant attention. This study aimed to assess the antidepressant and anxiolytic properties of luteolin (LTN), a potent antioxidant and anti-inflammatory component, using a 6-hydroxydopamine (6-OHDA)-induced animal model of PD. Rats were administered LTN (10, 25, and 50 mg/kg, per oral) and fluoxetine (10 mg/kg/per oral) over a 28-day period. Behavioral tests were employed to estimate the depression- and anxiety-like behaviors. Rats treated with LTN exhibited significant improvement in 6-OHDA-induced mood alterations, as per behavioral tests. Additionally, LTN treatment led to increased hippocampal levels of catalase and superoxide dismutase, and a reduction in malondialdehyde. LTN downregulated the gene expression of nuclear factor kappa B (NF-κB)/nod-like receptor (NLR) pyrin domain-containing 3 (NLRP3) axis components, including NF-κB, NLRP3, ASC, and Caspase1 and reduced the protein level of pro-inflammatory cytokines, including interleukin (IL)-6, interleukin (IL)-1β, and tumor necrosis factor alpha (TNF-α), in addition to augmenting the protein levels of TNF-α, IL-1β, and IL-6. Furthermore, LTN exhibited an upregulatory effect on the anti-inflammatory cytokine IL-10 within the hippocampus of 6-OHDA-induced PD rats. Also, molecular docking showed higher affinity between LTN and NF-κB/NLRP3 axis components. These findings highlight the potential anxiolytic and antidepressant impacts of LTN through its antioxidant and anti-inflammatory mechanisms against 6-OHDA-induced alterations in a rat PD model.

Observational studies and clinical trials indicate a link between arterial stiffness (AS) and sarcopenia (SAR), yet the causal relationship between these remains unclear. The study aims to investigate the causal connection from AS to SAR by Mendelian randomization (MR). We analyzed Genome-Wide Association Studies data for AS indicators: pulse wave arterial stiffness index (PWASI) and pulse wave peak-to-peak time (PPT), and SAR indicators: low hand grip strength (LHGS), usual walking pace (UWP), moderate-to-vigorous physical activity levels (MVPA), and walk or cycle unassisted for 10 minutes. The inverse variance-weighted, MR-Egger, weighted mode, and weighted median were applied to MR. There is a bidirectional causal relationship between the AS and SAR. The PWASI has a causation with UWP (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.94-0.99). The PPT has a causal association with MVPA (OR = 1.08, 95% CI = 1.002-1.144) and UWP (OR = 1.05, 95% CI = 1.017-1.096). The LHGS is causally associated with PPT (OR = 0.95, 95% CI = 0.91-0.98) and UWP has a causal association with PWASI (OR = 0.77, 95% CI = 0.65-0.90) and PPT (OR = 1.37, 95% CI = 1.17-1.60). The increased AS could reduce the motor ability slightly and the lower upper and lower limb strength could lead to the higher AS. This bidirectional causal relationship of the two may offer novel perspectives for advancing the understanding of the underlying mechanisms related to AS and muscle pathophysiology.

As a typical E3 ligase, tripartite motif-containing 65 (TRIM65), is implicated in the modulation of biological processes, such as metastasis, proliferation, and apoptosis. However, the function of TRIM65 in prostate cancer (PCa) and its potential mechanism have not yet been excavated. In this work, we affirmed Tripartite motif-containing protein 65 (TRIM65) as a new oncogene in PCa, which accelerated PCa cell proliferation and impeded cell ferroptosis. In vivo, depletion of TRIM65 inhibited PCa tumorigenesis and metastasis. Mechanically, our findings uncovered that TRIM65 enhances NKD inhibitor of WNT signaling pathway 2 (NKD2) degradation via the ubiquitin-proteasome signaling. TRIM65 facilitated proliferation and restricted ferroptosis via downregulating NKD2 levels. Moreover, TRIM65 activated the wingless-integrated/β-catenin pathway in PCa cells via inhibiting NKD2. Taken together, these data uncovered that TRIM65 controls PCa proliferation, and ferroptosis and regulates the Wnt/β-catenin signaling via directly targeting NKD2 for ubiquitination degradation. Our study provides insights into the multifaceted regulatory role of TRIM65 in the development of PCa, laying the foundation for exploring new therapeutic approaches.

Aging-related muscle atrophy/sarcopenia is the most common type of muscle impairment that affects the quality of life. In the current study, we examined the effect of a functional food mixture of amla, turmeric, black pepper, cinnamon, and ginger on D-galactose-induced muscle alterations in rats. Wistar rats were randomly divided into three groups: Control (C), D-galactose (G), and D-galactose + functional food mixture intervention (G + I). Rats in group-G and -G + I were injected with D-galactose (300 mg/kg/day) for 90 days. After 3 months of the experimental period, the rats were sacrificed to collect gastrocnemius muscle. Group-G rats showed elevated levels of inflammatory cytokines (TNFα and NF-kB), atrogenes (atrogin-1 and MuRF1), decreased insulin/IGF1 signaling (decreased AKT phosphorylation), altered mitochondrial dynamics (increased fission and decreased fusion proteins), increased apoptotic mediators (Bax/Bcl-2, and caspase-3), and decreased muscle cell cross-sectional area when compared with group-C (p < 0.05). Interestingly, supplementation with the functional food mixture prevented galactose-induced alterations in the muscle. The observed anti-inflammatory, insulin-sensitizing, mitochondria-protective, and antiapoptotic effects of the functional food could be the underlying mechanisms in displaying positive effects against galactose-induced muscle atrophy and, hence, may be useful for the prevention of age-related muscle disorders.

Frailty, a multifaceted syndrome, affects approximately 26% of older adults globally, yet there are limited data on the prevalence and longitudinal impact of frailty subtypes. Therefore, in this study, we aim to determine the prevalence of physical, psychological, and cognitive frailty, transitions between subtypes, and associated health determinants among Malaysian community-dwelling older adults. This study is part of the longitudinal aging study in Malaysia (LRGS Ageless and TUA). We assessed 815 older adults in 2014, with successful follow-up of 402 participants (mean age: 67.08 ± 5.38 years) after 5 years. Frailty subtypes were assessed at baseline, and transitions were evaluated at the 5-year mark. At baseline, the prevalence of older adults categorized as robust, physical frailty, cognitive frailty, and psychological frailty was 26.7%, 36.3%, 12.1%, and 16.7%, respectively, with 8.1% exhibiting concurrent psychological and cognitive frailty. Follow-up results showed that 22.9% remained robust, 46.8% experienced no change, 24.9% deteriorated (adversed), and 5.5% improved (reversed). Logistic regression analysis identified living alone (p < 0.001), increased body fat percentage (p < 0.05), increased waist circumference (p < 0.05), reduced fat-free mass (p < 0.05), decreased lower limb flexibility (p < 0.05), and declined cardiorespiratory fitness (p < 0.05) as significant predictors of frailty deterioration. Higher Mini Mental State Examination (MMSE) scores and improved Timed Up and Go and Chair Stand test results (p < 0.05) were significantly associated with the reversal of frailty subtypes (p < 0.05). Younger older adults (p < 0.001), males (p < 0.05), those with lower WHO Disability Scale scores (p < 0.05), and higher MMSE scores (p < 0.05) were significantly less likely to develop frailty subtypes. Intervention strategies that focus on combined physical, cognitive, and psychosocial functions are crucial for both reversing and preventing the progression of frailty subtypes in older adults.

Aging is an inevitable biological process that significantly impacts human health, leading to a decline in cellular function and an increase in cellular damage. This study elucidates the burgeoning potential of antiaging pharmaceuticals in mitigating the thriving burden of chronic conditions linked to advancing age. It underscores the pivotal role of these pharmacotherapeutic agents in fostering longevity free from debilitating age-related afflictions, notably cardiovascular disorders, neoplastic processes, and neurodegenerative pathologies. While commendable strides have been made evident in preclinical models, it is crucial to thoroughly investigate their effectiveness and safety in human groups. In addition, ethical concerns about fair access, societal impacts, and careful resource distribution are significant in discussions about developing and using antiaging medications. By approaching the development and utilization of antiaging medications with diligence and foresight, we can strive toward a future where individuals can enjoy extended lifespans free from the debilitating effects of age-related ailments.