Rejuvenation research最新文献

Beneficial genetic or environmental factors that influence the length and quality of life can be evaluated while studying supercentenarians. The oldest-old can withstand serious/fatal illnesses more than their peers and/or their aging rate is decreased. Supercentenarians are an interesting group of individuals whose lifestyle is not particularly healthy according to the common guidelines, namely some of them seem to have similar harmful behaviors, but still manage to stay healthier for longer, and while eventually dying from the same degenerative diseases as the general population, they develop symptoms 20-30 years later. As there are not many supercentenarians by definition, it is worthwhile to diligently collect their data to enable future meta-analyses on larger samples; much can be learned from supercentenarians' habits and lifestyle choices about the aging process. Contributions of genetics, lifestyle choices, and epigenetics to their extended life span are discussed here.

Non-enzymatic glycation (a.k.a. Maillard reaction) is a series of random spontaneous reactions between reducing sugars and amines, resulting in the formation of irreversible advanced glycation endproducts (AGE's). In food chemistry, this process is beneficial by contributing to the flavor, aroma, texture, and appearance of cooked foods. In vivo, however, Maillard reaction is deleterious because uncontrolled modification and crosslinking of biological macromolecules impairs their function. Consequently, chronic hyperglycemia of diabetes mellitus, for instance, leads to increased non-enzymatic glycation and diverse, multi-organ pathologies of diabetic complications. Based on the fact that toxic compounds, such as free radicals, are detoxified in vivo by specific defense mechanisms, one would expect to find mechanisms to control glucose toxicity as well. Thus far, only one such enzyme, fructosamine-3-kinase (FN3K), has been characterized. It operates intracellularly by catalyzing ATP-dependent removal of Maillard adducts, D-fructoselysines, from proteins, thereby reducing the Maillard reaction flux from glucose to AGE's. When FN3K was isolated, a closely related but distinct protein copurified with it. Unlike FN3K, however, this enzyme, fructosamine-3-kinase-related protein (FN3KRP), does not phosphorylate D-fructoselysines but it does phosphorylate several other (non-physiological) substrates. Interestingly, the distribution of FN3KRP in nature appears to be nearly universal whereas that of FN3K is limited to endotherms. In this article, it is suggested that the function of FN3KRP is deglycation of Maillard adducts downstream from fructoselysines. Such a mechanism, if proven correct, would be valuable given reports on apparent correlations between FN3KRP and some chronic conditions and/or diseases, such as a recent publication which proposes that the FN3KRP gene may be a longevity gene.

The main active metabolite of vitamin D, the 1,25-dihydroxyvitamin D (1,25(OH)₂D), and the shed form of the α-Klotho gene (S-Klotho) play an important role in aging-related physiological processes and are currently considered powerful antiaging renal biomarkers. We aimed to investigate the relationship between 1,25(OH)₂D and S-Klotho plasma levels in middle-aged sedentary healthy adults. We also aimed to study the mediation role of body composition, physical activity levels, dietary parameters, and blood markers in the association between 1,25(OH)₂D and S-Klotho plasma levels. A total of 73 middle-aged sedentary adults (53.4% women; 53.7 ± 5.1 years old) were enrolled in this cross-sectional study. The 1,25(OH)₂D plasma levels were measured using a DiaSorin Liaison^® immunochemiluminometric analyzer. S-Klotho plasma levels were measured using a solid-phase sandwich enzyme-linked immunosorbent assay. Body composition analysis was performed using dual-energy X-ray absorptiometry scanner. A tendency toward a negative association was observed between 1,25(OH)₂D and S-Klotho plasma levels (β = -0.222, R² = 0.049, p = 0.059). The association was attenuated after controlling for age and sex and become significant after controlling for fat mass index. In addition, the association between 1,25(OH)₂D and S-Klotho levels was indirectly influenced by bone mineral density (BMD), with a percentage of mediation of 31.40%. Our study shows that 1,25(OH)₂D is negatively associated with S-Klotho plasma levels in middle-aged sedentary adults, which is partially mediated by BMD. Clinicaltrial.gov: ID: NCT03334357.

An experimental novel antiaging intervention strategy is based on the concept of parabiosis, which involves long-term treatment with factors derived from young blood facilitating rejuvenation of old individuals. In this study, we employed blood plasma from young rats as an intervention strategy to evaluate whether this could impact aging biomarkers in aged rats. The biomarkers studied include: reactive oxygen species, the ferric reducing ability of plasma, plasma membrane redox system, reduced glutathione, malondialdehyde, protein carbonyl, and advanced oxidation protein products in blood. Additionally, the level of tumor necrosis factor-α and interleukin-6 were also estimated in blood. We found that old rats injected with plasma from young rats were protected from oxidative stress. Thus, this study provides some evidence of the rejuvenating effects of young plasma. We hypothesize that young plasma may contain certain "factors," which may be responsible for the observed effects. The mechanism of action is not clearly understood and is open to further studies.

Clinically viable screening tools for detecting individuals at heightened risk for mobility limitations is warranted. However, it remains unclear in acutely hospitalized patients (>75 years) whether handgrip strength might be a good predictor for "proxy" muscle strength. To examine the reliability and validity of handgrip strength test in acute hospitalized older adults in comparison with other standardized muscular strength tests, and to examine its ability to discriminate between presence and absence of mobility limitations. Cross-sectional study. A total of 234 patients (mean age 87.0 years, 46% women) admitted to a tertiary public hospital between 2016 and 2017 were recruited. Maximal (one repetition maximum) and power muscle output of the upper and lower extremity along with functional capacity (as assessed with Barthel index and the Short Physical Performance Battery [SPPB]), and cognitive function was measured at admission. Functional impairment (mobility limitations) was defined at SPPB ≤7 points. Pearson's correlation and multivariable linear regression were evaluated between handgrip test and maximal and muscle power output as the reference method to assess concurrent validity. Receiver operating characteristic analysis was used to estimate handgrip strength cutoff point for likelihood of mobility limitations to assess predictive validity. Findings show moderate-to-strong correlations between standardized muscular strength (reference methods) and handgrip strength test (r = 0.534-0.725). All muscular strength tests show moderate accuracy (area under curve >0.7). Handgrip strength shows the higher positive predictive value (87%) and, therefore, a lower number of false positives. The overall handgrip strength cutoff point for likelihood of mobility limitations was 18.4 kg for men and women. Handgrip strength may be a useful tool for detecting acutely hospitalized older who are at risk of mobility limitations and could aid in focusing interventions on those with higher risk. Randomized clinical trial: NCT02300896.

Resistance training (RT) is considered a viable strategy to enhance the autonomy and functionality of older populations. We randomized 49 older women (64.2 ± 3.8) into one of two groups: an intervention group (IG) (n = 29) that performed regimented RT or a nontraining control group (CG) (n = 20). The RT protocol was carried out three times a week for both the upper and lower limbs over a 12-week study period. A 30-second arm flexion test was used to test upper limb endurance and a 30-second chair stand test was used to analyze lower limb endurance. Dynamic balance was tested by a Y balance test normalized by leg length. A Soda Pop test was employed to analyze coordination. Results showed significant improvements in IG versus CG in both upper limb (19.50 ± 1.52 vs. 11.40 ± 2.87, p = 0.001) and lower limb muscular endurance (14.90 ± 3.10 vs. 26.56 ± 3.17, p = 0.001). Moreover, the training group showed superior improvements in anterior and posterolateral balance compared to CG (63.9% ± 3.1% to 70.2 ± 2.1 and 88.1 ± 3.9 to 94.2 ± 2.7 with p = 0.001, respectively). There were no significant differences in coordination outcomes between groups. In conclusion, we demonstrate that RT is effective in developing muscular endurance and dynamic balance in postmenopausal women, but does not influence muscular coordination in the measures studied. Study registered in the Brazilian Registry Clinical Trials Registry (No. RBR-7MZ2KR).

Intermittent fasting (IF) is the practice of restricting food intake for 12-48 hours per fasting cycle over a prolonged period of time. Previous study shows beneficial health effects such as weight loss and lower risk for cardiometabolic diseases. Although reduced calorie intake may account for some of the observed benefits of IF, exact mechanisms are still unclear. Recent evidence indicates that IF may lead to remodeling and increased taxonomic diversity in the human gut microbiome. In particular, the Lachnospiraceae family of anaerobic bacteria increased during fasting. This family, in the order Clostridiales, promotes butryogenesis in the gut, a process that is associated with healthful metabolic and prolongevity effects. IF-associated alterations to the microbiome may play a key role in the metabolic and potential healthspan-enhancing benefits of IF and dietary restriction.

High sucrose can induce tau hyperphosphorylation and cognitive dysfunction/memory impairment as observed in Alzheimer's disease (AD). Rutaecarpine, a specific (transient receptor potential vanilloid 1 [TRPV1]) agonist, is neuroprotective against high sucrose diet-induced impairment, but detailed mechanisms are still elusive. In this study, we investigated whether rutaecarpine mitigates high sucrose diet-induced pathological alterations and cognitive in AD-like mice. Mice were administered fodder containing 0.01% rutaecarpine and 20% sucrose solution. Our results showed that rutaecarpine significantly attenuated high sucrose diet-induced spatial memory impairment and enhanced synaptic plasticity; rutaecarpine prevented high sucrose diet-induced tau hyperphosphorylation by decreasing glycogen synthase kinase-3β (GSK-3β) activity; activation of GSK-3β reversed the protective effect of rutaecarpine on learning and memory deficits, synaptic plasticity, and tau hyperphosphorylation induced by high-glucose diet significantly, suggesting that GSK-3β activation is required for high glucose-induced tau hyperphosphorylation. These results demonstrated that rutaecarpine can mitigate high sucrose diet-induced hyperphosphorylation of AD-associated tau protein and cognitive impairment by inhibiting GSK-3β, which supported that dietary rutaecarpine might have a promising use for therapeutic intervention of AD.

Astaxanthin (AST), a xanthophyll belonging to the family of carotenoids, is a potent antioxidant. The effect of AST on longevity and its physiological and molecular mechanism are still unclear. In this study, we proved that AST could prolong the life span of Caenorhabditis elegans. To uncover whether AST could delay aging by upregulating autophagy, we measured the expression of autophagy gene and the life span of autophagy gene bec-1 mutant nematodes, and the results showed that the expression of autophagy gene was upregulated after AST intervention and the disruption of bec-1 weakened the extension of the life span. To explore the molecular mechanism of AST-induced autophagy upregulation, we knocked out the daf-16 or hlh-30 (key genes of insulin/insulin growth factor-1 [IGF-1] signal pathway or target of rapamycin [TOR] signal pathway) by RNA interference, and the expression of autophagy gene lgg-1 decreased. Collectively, our results strongly suggest that autophagy, which is both the insulin/IGF-1 signal pathway dependent and TOR signal pathway dependent, plays a role in the prolongation of the life span of Caenorhabditis elegans by AST.