Objective:To examine the correlation between serum Klotho levels and frailty in elderly people.Methods:In this cross-sectional study, 150 community-dwelling elderly people aged 65 years and over were enrolled.Subjects were divided into a frail(n=50, 33.3%), a pre-frail(n=47, 31.3%)and a non-frail(n=53, 35.3%)group based on the Fried phenotype.General participant data, routine laboratory test results, short physical performance battery(SPPB)results and human body composition data were collected.Serum Klotho protein levels were measured by an enzyme-linked immunosorbent assay.The relationship between serum Klotho protein levels and frailty was analyzed by using Spearmen's correlation analysis and Logistic regression analysis.Results:Klotho protein levels were lower in the frail group than in the non-frail group( P=0.001), whereas differences between the frail group and the pre-frail group and between the pre-frail group and the non-frail group were not statistically significant(all P>0.05).When Klotho protein levels were classified into four quartiles, i.e., Q 1, Q 2, Q 3, and Q 4, using three cut-off vales(2.28, 3.52, and 5.09 mg/L), the prevalences of frailty were 51.4%(19/37), 39.5%(15/38), 24.3%(9/37)and 18.4%(7/38), respectively.The prevalence of frailty decreased with increasing Klotho protein levels( χ2=11.204, P=0.011).Spearman correlation analysis showed that the Klotho protein level was negatively correlated with frailty( r=-0.310, P<0.001).Multivariate Logistic regression analysis results showed that age( OR=1.109, 95% CI: 1.011-1.217, P=0.028)and sarcopenia( OR=6.511, 95% CI: 1.279-33.147, P=0.024)were risk factors for frailty, while walking( OR=0.104, 95% CI: 0.033-0.326, P<0.001), a high SPPB score( OR=0.780, 95% CI: 0.627-0.970, P=0.026), and a high Klotho protein level( OR=0.752, 95% CI: 0.581-0.974, P=0.031)were protective factors against frailty. Conclusions:The serum Klotho protein level may be used as a parameter for the assessment of frailty.It is negatively correlated with frailty, suggesting that elderly people with low serum Klotho protein levels are at high risk of developing frailty.

ObjectiveTo investigate the effects of jujuboside A （JuA） on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment （VCI） and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group （n=10）， a blank control group （n=10）， and a modeling group （n=30）. The rats in the modeling group underwent bilateral carotid artery ligation （2-VO） for the modeling of VCI. After stabilization， the VCI rats were randomized into model， JuA （20 mg·kg^-¹）， and donepezil （0.45 mg·kg^-¹） groups. After 4 weeks of gavage， the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β （GSK-3β）， cAMP response element-binding protein （CREB）， B cell lymphoma-2 （Bcl-2）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β， p-GSK-3β， p-CREB， Bcl-2， PI3K， p-PI3K， Akt， and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group， the model group exhibited declines in the learning and memory abilities （P<0.01）， neuronal damage and decreased neurons in the hippocampal CA1 region （P<0.01）， up-regulation in the mRNA level of GSK-3β （P<0.01）， and down-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2， as well as the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.01）. In comparison to the model group， both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities （P<0.05， P<0.01）， with reduced neuronal damage and increased neurons （P<0.05， P<0.01）. In addition， the two groups showed down-regulation in the mRNA level of GSK-3β （P<0.01） and up-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2 and the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.05， P<0.01）. There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities， neuron count， and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway， reducing the apoptosis of hippocampal neurons， and alleviating the hippocampal neuronal damage.