Rejuvenation research最新文献

Here presented for the first time are results showing persistence over a 5+ year period in a human who had a hormone gene therapy administered to muscle. This growth hormone releasing hormone (GHRH) therapy was administered in two doses, a year apart, with a mean after the second dose of 195 ng/mL (13 × normal, σ = 143, σ_M = 34, max = 495, min = 53). This level of GHRH therapy appears to be safe for the subject, although there were some adverse events. Insulin-like growth factor 1 levels were little affected, nor were the growth hormone test results, showing no indications of acromegaly for the hormone homologue used. Heart rate declined 8 to 13 bpm, persistent over 5 years. Testosterone rose by 52% (σ = 22%, σ_M = 6%). The high-density lipoprotein/low-density lipoprotein ratio dropped from 3.61 to mean 2.81 (σ = 0.26, σ_M = 0.057, max = 3.3, min = 2.5), and triglycerides declined from 196 mg/dL to mean 94.4 mg/dL (σ = 21.9, σ_M = 5.0, min = 59, max = 133, min = 59). White blood cell counts increased, however, the baseline was not strong. CD4 and CD8 mean increased by11.7% (σ = 11.6%, σ_M = 3.3%, max = 30.7%, min = -9.6%) and 12.0% (σ = 10.5%, σ_M = 3.0%, max = 29.1%, min = -6.7%), respectively. Ancillary observations comprise an early period of euphoria, and a dramatic improvement in visual correction after the first dose, spherical correction from baseline (L/R) -2.25/-2.75 to -0.25/-0.5. Over the next 5 years, correction drifted back to -1.25/-1.75. Horvath PhenoAge was cut 44.1% post-treatment. At completion, epigenetic age was -6 years (-9.3%), and telomere age was +7 months (+0.9%).

Although we have found that increased serum levels of glyceraldehyde-derived advanced glycation end products (AGEs) are associated with numerous aging-related disorders, it remains unclear which structurally distinct AGEs could be a reliable biomarker of the healthy life-threatening disorders. Since pentosidine is produced by glyceraldehyde, we measured here urinary pentosidine levels with a newly developed enzyme-linked immunosorbent assay (ELISA) kit, which requires no pretreatment with acid hydrolysis and heat, and examined their correlations with geriatric syndrome, such as musculoskeletal disease, frailty, and cognitive impairment, in a general population. Multiple regression analysis revealed that female, age, history of fracture after fall, and taking medication for diabetes were independent correlates of log urine pentosidine-to-creatinine ratio (R² = 0.190). When gender-adjusted log urine pentosidine-to-creatinine ratio stratified by smile frequency grade was compared using analysis of covariance, urine pentosidine-to-creatinine ratio was significantly decreased according to the increase in smile frequency. Our present findings suggest that measurement of urine pentosidine-to-creatinine ratio by a newly developed ELISA kit may be useful for identifying high-risk patients for fall-related fractures.

Exercise for presbyopia is theoretically ineffective. However, some studies have reported favorable subject responses, although the reasons were not detected. We investigated one such presbyopic exercise. Twenty-three volunteers (48.5 ± 5.0 years) viewed near (30-40 cm) and far (>5 m) points back and forth 20 times in one set and repeated this four times daily. After 2 months, the accommodation or near visual acuity did not improve. The pupillary size under accommodative stimulation decreased significantly (p = 0.04) from 4.03 ± 0.84 to 3.75 ± 0.98 mm, and the convergence amounts increased significantly (p = 0.03) from 0.71 ± 0.25 to 0.98 ± 0.46 mm. The overall satisfaction with the near vision improved significantly (p = 0.02). The changes in the pupillary sizes and convergence amounts did not differ between subjects with improved satisfaction (positive group) and those without improvement (negative group) (p = 0.50 and p = 0.94, respectively). The pupillary size after exercise was significantly (p = 0.04) smaller in the positive group (3.19 ± 0.82) than in the negative group (4.08 ± 0.94). In conclusion, the exercise for presbyopia was fundamentally ineffective to improve accommodation, however, it strengthened miosis while viewing near and might improve satisfaction for near vision. (Clinical Trial Registration number: UMIN000023561).

Metformin, a commonly used well-tolerated treatment for type 2 diabetes, is being deployed in clinical trials to ameliorate aging in older nondiabetic humans. Concerningly, some experiments in model organisms have suggested that metformin use at old ages shortens life span and is toxic to mitochondria. The demonstrated safety of metformin therapy in humans and the conflicting data from model organisms compelled us to test the hypothesis that metformin treatment would be toxic to older rats. To define an effective dose in 30-month-old hybrid rats, we evaluated two doses of metformin (0.1%, 0.75% of the diet) and treated the rats for 4 months. Body mass decreased at the 0.75% dose. Neither dose affected mortality between 30 and 34 months of age. We assessed mitochondrial integrity by measuring mitochondrial DNA (mtDNA) copy number and deletion mutation frequency, and mitochondrial respiration in skeletal muscle and the heart. In skeletal muscle, we observed no effect of metformin on quadriceps mass, mtDNA copy number, or deletion frequency. In the heart, metformin-treated rats had higher mtDNA copy number, lower cardiac mass, with no change in mtDNA deletion frequency. Metformin treatment resulted in lower mitochondrial complex I-dependent respiration in the heart. We found that, in old rats, metformin did not compromise mtDNA integrity, did not affect mortality, and may have cardiac benefits. These data provide some reassurance that a metformin intervention in aged mammals is not toxic at appropriate doses.

In our recent transcriptomic meta-analysis, we used random forest machine learning to accurately predict age in human blood, bone, brain, heart, and retina tissues given gene inputs. Although each tissue-specific model utilized a unique number of genes for age prediction, we found that the following six genes were prioritized in all five tissues: CHI3L2, CIDEC, FCGR3A, RPS4Y1, SLC11A1, and VTCN1. Since being selected for age prediction in multiple tissues is unique, we decided to explore these pan-tissue clock genes in greater detail. In the present study, we began by performing over-representation and network topology-based enrichment analyses in the Gene Ontology Biological Process database. These analyses revealed that the immunological terms "response to protozoan," "immune response," and "positive regulation of immune system process" were significantly enriched by these clock inputs. Expression analyses in mouse and human tissues identified that these inputs are frequently upregulated or downregulated with age. A detailed literature search showed that all six genes had noteworthy connections to age-related disease. For example, mice deficient in Cidec are protected against various metabolic defects, while suppressing VTCN1 inhibits age-related cancers in mouse models. Using a large multitissue transcriptomic dataset, we additionally generate a novel, minimalistic aging clock that can predict human age using just these six genes as inputs. Taken all together, these six genes are connected to diverse aspects of aging.

Healthspan science aims to add healthy, functional years to human life. Many different methods of improving healthspan have been investigated, chiefly focusing on just one aspect of an organism's health such as survival. Studies in Drosophila melanogaster have demonstrated that a reversal to a long-abandoned ancestral diet results in improved functional health, particularly at later ages. Meanwhile, pharmaceutical studies have demonstrated that botanical extracts have potent antiaging properties, capable of extending the mean lifespan of D. melanogaster by up to 25%, without a decrease in early fecundity. In this study, we combine these two different approaches to healthspan extension to examine whether a combination of such treatments results in a synergistic or antagonistic effect on Drosophila healthspan. One botanical extract, derived from Rhodiola rosea, mimicked the effects of the ancestral apple diet with better performance at later ages compared with the control. Another extract, derived from Rosa damascena, decreased age-specific survivorship when combined with the apple diet providing support for the "Poisoned Chalice" hypothesis that combinations of various supplements or diets can elicit adverse physiological responses. More experiments in model organisms should be completed researching the effects of combining healthspan-extending substances in various diet backgrounds.

Several studies claimed C₆₀ fullerenes as a prospective geroprotector drug due to their ability to capture free radicals effectively and caused a profound interest in C₆₀ in life extension communities. Multiple additives are already sold for human consumption despite a small body of evidence supporting the beneficial effects of fullerenes on the lifespan. To test the effect of C₆₀ fullerenes on lifespan and healthspan, we administered C₆₀ fullerenes dissolved in virgin olive oil orally to 10-12 months old CBA/Ca mice of both genders for 7 months and assessed their survival. To uncover C₆₀ and virgin olive effects, we established two control groups: mice treated with virgin olive oil (vehicle) and mice treated with drinking water. To measure healthspan, we conducted daily monitoring of health condition and lethality and monthly bodyweight measurements. We also assessed physical activity, glucose metabolism, and hematological parameters every 3 months. We did not observe health deterioration in the animals treated with C₆₀ compared with the control groups. Treatment of mice with C₆₀ fullerenes resulted in an increased lifespan of males and females compared with the olive oil-treated animals. The lifespan of C₆₀-treated mice was similar to the mice treated with water. These results suggest that the lifespan-extending effect in C₆₀-treated mice appears due to the protective effect of fullerenes in opposition to the negative effect of olive oil in CBA/Ca mice.

Numerous studies demonstrate a global decrease in nicotinamide adenine dinucleotide (NAD+) with aging. This decline is associated with the development of several of the hallmarks of aging such as reduced mitophagy and neuroinflammation, processes thought to play a significant role in the progression of Alzheimer's disease (AD). Augmentation of NAD+ by oral administration of a precursor, nicotinamide riboside (NR), reduces senescence of affected cells, attenuates DNA damage and neuroinflammation in the transgenic APP/PS1 murine model of AD. Inflammation mediated by microglial cells plays an important role in progression of AD and other neurodegenerative diseases. The cytoplasmic DNA sensor, cyclic GMP-AMP synthase (cGAS) and downstream stimulator of interferon genes (STING), generates an interferon signature characteristic of senescence and inflammaging in the brain of AD mice. Elevated cGAS-STING observed in the AD mouse brains and human AD fibroblasts was normalized by NR. This intervention also increased mitophagy with improved cognition and behavior in the APP/PS1 mice. These studies suggest that modulation of the cGAS-STING pathway may benefit AD patients and possibly other disorders characterized by compromised mitophagy and excessive neuroinflammation.

Ageism is an important phenomenon that affects individuals and how society relates to older adults. It is important to evaluate ageism in the medical staff because of its potential effect on treatment for older adults. A cross-sectional study to assess the negative attitudes of doctors and nurses toward older adults was conducted using the Fraboni Scale of Ageism (FSA), a method for evaluating attitudes toward ageism in medical teams. Additional variables associated with ageism such as aging anxiety, and death and dying anxiety were also assessed. The study population included doctors and nurses working in a large university hospital or in community clinics in southern Israel. In all, 431 questionnaires were collected, 203 from the hospital (47.5%) and 224 from the community (52.5%). Of these, 216 (50.1%) were from doctors and 215 (49.9%) from nurses. The mean ageism score in the FSA was 2.8. In a linear regression model, doctors were less ageist than nurses; ageism was directly associated with aging anxiety, and dying anxiety, and was inversely associated with death anxiety. Among doctors, prominent ageist attitudes were directly associated with aging and dying anxiety, inversely associated with graduation from medical school in Israel, and death anxiety. Among nurses, prominent ageism attitudes were directly associated with dying anxiety and inversely associated with work in the hospital. Ageist attitudes were found among doctors and nurses in both the hospital and community clinics. The results emphasize the need to raise awareness of ageism in medical teams and to include this subject in professional training programs designed to reduce its prevalence.

Chitosan is a polysaccharide made up of β1,4-linked d-glucosamine (GlcN) and N-acetyl-GlcN. In this study, we evaluated the possible caloric restriction mimetic (CRM) effect of dietary chitosan on systemic redox status, inflammatory biomarkers, and lipid profile in plasma and erythrocyte samples of d-galactose-induced mimetically aged rats. We found a significant increase (p < 0.05) in the reactive oxygen species, protein carbonyl, fasting glucose, body weight, cholesterol, triglyceride, inflammatory markers-interleukin-6 and tumor necrosis factor-alpha in an accelerated senescent rat model. There was also a significant decrease (p < 0.05) in glutathione, advanced glycation end product in senescent rats. Chitosan treatment increased ferric-reducing antioxidant potential, glutathione, plasma membrane-reduced system in accelerated senescent model of rats. Our finding suggests that chitosan has properties similar to a CRM and can effectively maintain the redox homeostasis during the aging process in rat erythrocytes.