Grip Strength is a Predictor for Subsyndromal Delirium Among Older Adults Following Joint Replacement.

Background: Delirium is common in older patients during the postoperative period, increasing the number of adverse events, and grip strength is associated with delirium. Subsyndromal delirium (SSD) is a prostate of clinical delirium; nevertheless, the relationship between grip strength and SSD has not been elucidated. This study aimed to examine the association between grip strength and SSD in the elderly after arthroplasty. Methods: A total of 181 patients were recruited from two Chinese hospitals. SSD and delirium were evaluated before the surgery and the first week after surgery using the confusion assessment method. The Mini-mental State Examination was used to assess patients' cognitive function, and their grip strength was evaluated with an electronic hand dynamometer before surgery. Logistic regression and ROC curve analysis were conducted to determine the odds ratio and predictive value of grip strength for SSD. Results: The incidence of SSD and postoperative delirium (POD) was 41.44% and 14.36% for the elderly following arthroplasty respectively, and approximately 1/3 of SSD progressed into POD. Older age, declined cognitive function, fall history, and lower grip strength were risk factors for SSD (P<0.05). The area under the ROC curve of grip strength was 0.863 and 0.900 for males and females respectively, and the cut-off point of it was determined to be 22.050 kg for men and 18.050 kg for women. Conclusion: SSD and POD are common among older people. Decreased grip strength, advanced age, lower cognitive function, and fall history were independent risk factors for SSD, and grip strength was a significant predictor for SSD in aged patients after the arthroplasty.

Young donor hematopoietic stem cells revitalize aged or damaged bone marrow niche by transdifferentiating into functional niche cells.

The bone marrow niche maintains hematopoietic stem cell (HSC) homeostasis and declines in function in the physiologically aging population and in patients with hematological malignancies. A fundamental question is now whether and how HSCs are able to renew or repair their niche. Here, we show that disabling HSCs based on disrupting autophagy accelerated niche aging in mice, whereas transplantation of young, but not aged or impaired, donor HSCs normalized niche cell populations and restored niche factors in host mice carrying an artificially harassed niche and in physiologically aged host mice, as well as in leukemia patients. Mechanistically, HSCs, identified using a donor lineage fluorescence-tracing system, transdifferentiate in an autophagy-dependent manner into functional niche cells in the host that include mesenchymal stromal cells and endothelial cells, previously regarded as "nonhematopoietic" sources. Our findings thus identify young donor HSCs as a primary parental source of the niche, thereby suggesting a clinical solution to revitalizing aged or damaged bone marrow hematopoietic niche.

Transcutaneous electrical acupoint stimulation combined with an integrated perioperative nursing program prevents subsyndromal delirium in older patients after joint replacement.

OBJECTIVES: This study aimed to develop transcutaneous electrical acupoint stimulation combined with an integrated perioperative nursing program and evaluate its effects on preventing subsyndromal delirium (SSD) and postoperative delirium (POD) in older patients after joint replacement surgery. METHODS: Participants were randomly divided into two groups, the experimental group (n = 48) was given transcutaneous electrical acupoint stimulation combined with an integrated perioperative nursing program based on the routine care of the control group (n = 49). The incidence of SSD and POD in a week after surgery was recorded. Assessments of delirium severity, cognition, anxiety, and depression were also conducted at baseline and on postoperative day 7. RESULTS: The findings indicate that the intervention program had significant advances in alleviating the severity of delirium, cognitive impairment, anxiety, and depression but failed to reduce the incidence of SSD and POD. CONCLUSIONS: Our study indicated that TEAS combined with an integrated perioperative nursing program has a beneficial effect on alleviating symptoms of delirium, cognitive dysfunction, anxiety, and depression in older adults after joint replacement surgery.

Loss of Atg7 causes chaotic nucleosome assembly of mouse bone marrow CD11b+Ly6G- myeloid cells.

Atg7, a critical component of autophagy machinery, is essential for counteracting hematopoietic aging. However, the non-autophagic role of Atg7 on hematopoietic cells remains fundamentally unclear. In this study, we found that loss of Atg7, but not Atg5, another autophagy-essential gene, in the hematopoietic system reduces CD11b myeloid cellularity including CD11b+Ly6G+ and CD11b+Ly6G- populations in mouse bone marrow. Surprisingly, Atg7 deletion causes abnormally accumulated histone H3.1 to be overwhelmingly trapped in the cytoplasm in the CD11b+Ly6G-, but not the CD11b+Ly6G+ compartment. RNA profiling revealed extensively chaotic expression of the genes required in nucleosome assembly. Functional assays further indicated upregulated aging markers in the CD11b+Ly6G- population. Therefore, our study suggests that Atg7 is essential for maintaining proper nucleosome assembly and limiting aging in the bone marrow CD11b+Ly6G- population.

Autophagy-Sirt3 axis decelerates hematopoietic aging.

Autophagy suppresses mitochondrial metabolism to preserve hematopoietic stem cells (HSCs) in mice. However, the mechanism by which autophagy regulates hematopoietic aging, in particular in humans, has largely been unexplored. Here, we demonstrate that reduction of autophagy in both hematopoietic cells and their stem cells is associated with aged hematopoiesis in human population. Mechanistically, autophagy delays hematopoietic aging by activating the downstream expression of Sirt3, a key mitochondrial protein capable of rejuvenating blood. Sirt3 is the most abundant Sirtuin family member in HSC-enriched population, though it declines as the capacity for autophagy deteriorates with aging. Activation of autophagy upregulates Sirt3 in wild-type mice, whereas in autophagy-defective mice, Sirt3 expression is crippled in the entire hematopoietic hierarchy, but forced expression of Sirt3 in HSC-enriched cells reduces oxidative stress and prevents accelerated hematopoietic aging from autophagy defect. Importantly, the upregulation of Sirt3 by manipulation of autophagy is validated in human HSC-enriched cells. Thus, our results identify an autophagy-Sirt3 axis in regulating hematopoietic aging and suggest a possible interventional solution to human blood rejuvenation via activation of the axis.

Deterioration of hematopoietic autophagy is linked to osteoporosis.

Hematopoietic disorders are known to increase the risk of complications such as osteoporosis. However, a direct link between hematopoietic cellular disorders and osteoporosis has been elusive. Here, we demonstrate that the deterioration of hematopoietic autophagy is coupled with osteoporosis in humans. With a conditional mouse model in which autophagy in the hematopoietic system is disrupted by deletion of the Atg7 gene, we show that incapacitating hematopoietic autophagy causes bone loss and perturbs osteocyte homeostasis. Induction of osteoporosis, either by ovariectomy, which blocks estrogen secretion, or by injection of ferric ammonium citrate to induce iron overload, causes dysfunction in the hematopoietic stem and progenitor cells (HSPCs) similar to that found in autophagy-defective mice. Transcriptomic analysis of HSPCs suggests promotion of iron activity and inhibition of osteocyte differentiation and calcium metabolism by hematopoietic autophagy defect, while proteomic profiling of bone tissue proteins indicates disturbance of the extracellular matrix pathway that includes collagen family members. Finally, screening for expression of selected genes and an immunohistological assay identifies severe impairments in H vessels in the bone tissue, which results in disconnection of osteocytes from hematopoietic cells in the autophagy-defective mice. We therefore propose that hematopoietic autophagy is required for the integrity of H vessels that bridge blood and bone cells and that its deterioration leads to osteoporosis.

Blood autophagy defect causes accelerated non-hematopoietic organ aging.

Autophagy has been well studied in regulating aging; however, the impact of autophagy in one organ on the aging of other organs has not been documented. In this study, we used a mouse model with deletion of an autophagy-essential gene Atg7 in hematopoietic system to evaluate the intrinsic role of hematopoietic autophagy on the aging of non-hematopoietic organs. We found that autophagy defect in hematopoietic system causes growth retardation and shortened lifespan, along with aging-like phenotypes including hypertrophic heart, lung and spleen, but atrophic thymus and reduced bone mineral density at organismal level. Hematopoietic autophagy defect also causes increased oxidative stress and mitochondrial mass or aging gene expression at cellular level in multiple non-hematopoietic organs. The organ aging in the Atg7-deleted mice was reversed by anatomic connection to wild-type mice with intact blood autophagy via parabiosis, but not by injection of blood cell-free plasma. Our finding thus highlights an essential role of hematopoietic autophagy for decelerating aging in non-hematopoietic organs.

Molecular cloning and expression characterization of translationally controlled tumor protein in silkworm pupae.

A Bombyx mori (B. mori) cDNA was isolated from silkworm pupae cDNA library encoding a homologue of translationally controlled tumor protein (BmTCTPk). BmTCTPk was expressed in E. coli; SDS-PAGE and Western blot showed the molecular weight of recombinant and native BmTCTPk is approximately 28 and 25 kDa, respectively; they are larger than the theoretical molecular weight. Immunohistochemical studies showed that BmTCTPk is uniformly distributed throughout the cytoplasm of BmN cells. In silkworm pupae, BmTCTPk is expressed in the midgut wall, the midgut cavity, and some fat body tissues lying between the midgut wall and body wall. Western blot and ELISAs performed on total protein extracts isolated from silkworm pupae at different development stages showed that, although BmTCTPk is expressed during all pupae stages, its expression level increases dramatically during late pupae stages, suggesting that BmTCTPk may play an important role during the developmental transition from pupa to imago.