Rejuvenation research最新文献

Experimental approaches such as Heterochronic Plasma Transfer (HPT) provide insights into the aging process and help identify the factors that impact aging, with the aim of developing anti-aging therapies. HPT involves the transfer of plasma from an animal of one age to an animal of a different age and highlights the effects of the systemic environment on aging. Despite its importance as an aging research tool, HPT is not without limitations and HPT experiments across various studies differ in key experimental designs considerations, presenting a challenge in obtaining comparable outcomes. In this review, we examine the caveats and experimental design considerations of HPT as a research tool. We provide insights into plasma preparation procedures, route of administration, dosing regimen, and appropriate controls to assist investigators in achieving their experimental goals.

We previously demonstrated that a 50% caloric restriction (CR) from birth improves several cardiometabolic risk factors in young rats. In this study, we investigated in middle-aged rats the consequences of a 50% CR from birth on cardiometabolic risk factors, heart function/morphology, ventricular arrhythmia, and fibrillation incidence, and cardiac intracellular proteins involved with redox status and cell survival. From birth to the age of 18 months, rats were divided into an Ad Libitum (AL18) group, which had free access to food, and a CR18 group, which had food limited to 50% of that consumed by the AL18. Resting metabolic rate, blood pressure, and heart rate were recorded, and oral glucose and intraperitoneal insulin tolerance tests were performed. Blood was collected for biochemical analyses, and visceral fat and liver were harvested and weighed. Hearts were harvested for cardiac function, histological, redox status, and western blot analyses. The 50% CR from birth potentially reduced several cardiometabolic risk factors in 18-month-old rats. Moreover, compared with AL18, the CR18 group showed a ∼50% increase in cardiac contractility and relaxation, nearly three to five times less incidence of ventricular arrhythmia and fibrillation, ∼18% lower cardiomyocyte diameter, and ∼60% lower cardiac fibrosis. CR18 hearts also improved biomarkers of antioxidant defense and cell survival. Collectively, these results reveal several metabolic and cardiac antiaging effects of a 50% CR from birth in middle-aged rats.

The amount of sleep needed over one's lifespan is age dependent and not sleeping enough or sleeping in excess is associated with increased morbidity and mortality. Yet, the convergent molecular mechanisms that link longevity and sleep are largely unknown. We performed a gene enrichment study that (1) identified genes associated with both longevity and sleep traits and (2) determined molecular pathways enriched among these shared genes. We manually curated two sets of genes, one associated with longevity and aging and the other with sleep traits (e.g., insomnia, narcolepsy, sleep duration, chronotype, among others), with both gene lists heavily driven by hits from recent large-scale Genome-Wide Association Studies. There were 47 overlapping genes between the gene list associated with sleep traits (1064 genes total) and the genes associated with longevity (367 genes total), indicating significantly more overlap than expected by chance. An overrepresentation analysis identified enriched pathways that suggest endocrine and epigenetic regulation as potential shared mechanisms between sleep traits and longevity. Concordantly, functional network analysis retrieved two clusters, being one associated with proteins of nuclear functions and the other, with extracellular proteins. This overlapping gene set, and the highlighted biological pathways may serve as preliminary findings for new functional investigations of sleep and longevity shared genetic mechanisms.

Effective cryopreservation of large tissues, limbs, and organs has the potential to revolutionize medical post-trauma reconstruction options and organ preservation and transplantation procedures. To date, vitrification and directional freezing are the only viable methods for long-term organ or tissue preservation, but are of limited clinical relevance. This work aimed to develop a vitrification-based approach that will enable the long-term survival and functional recovery of large tissues and limbs following transplantation. The presented novel two-stage cooling process involves rapid specimen cooling to subzero temperatures, followed by gradual cooling to the vitrification solution (VS) and tissue glass transition temperature. Flap cooling and storage were only feasible at temperatures equal to or slightly lower than the VS Tg (i.e., -135°C). Vascularized rat groin flaps and below-the-knee (BTK) hind limb transplants cryopreserved using this approach exhibited long-term survival (>30 days) following transplantation to rats. BTK-limb recovery included hair regrowth, normal peripheral blood flow, and normal skin, fat, and muscle histology. Above all, BTK limbs were reinnervated, enabling rats to sense pain in the cryopreserved limb. These findings provide a strong foundation for the development of a long-term large-tissue, limb and organ preservation protocol for clinical use.

T cells play critical roles in the immune system, including in responses to cancer, autoimmunity, and tissue regeneration. T cells arise from common lymphoid progenitors (CLPs) that differentiate from hematopoietic stem cells in the bone marrow. CLPs then traffic to the thymus, where they undergo thymopoiesis through a number of selection steps, resulting in mature single positive naive CD4 helper or CD8 cytotoxic T cells. Naive T cells are home to secondary lymphoid organs like lymph nodes and are primed by antigen-presenting cells, which scavenge for both foreign and self-antigens. Effector T cell function is multifaceted, including direct target cell lysis and secretion of cytokines, which regulate the functions of other immune cells (refer to "Graphical Abstract"). This review will discuss T cell development and function, from the development of lymphoid progenitors in the bone marrow to principles that govern T cell effector function and dysfunction, specifically within the context of cancer.

Acarbose (ACA), a well-studied and effective inhibitor of α-amylase and α-glucosidase, is a postprandial-acting antidiabetic medicine. The membrane of the erythrocyte is an excellent tool for analyzing different physiological and biochemical activities since it experiences a range of metabolic alterations throughout aging. It is uncertain if ACA modulates erythrocyte membrane activities in an age-dependent manner. As a result, the current study was conducted to explore the influence of ACA on age-dependent deteriorated functions of transporters/exchangers, disrupted levels of various biomarkers such as lipid hydroperoxides (LHs), protein carbonyl (PCO), sialic acid (SA), total thiol (-SH), and erythrocyte membrane osmotic fragility. In addition to a concurrent increase in Na⁺/H⁺ exchanger activity and concentration of LH, PCO, and osmotic fragility, we also detected a considerable decrease in membrane-linked activities of Ca²⁺-ATPase (PMCA) and Na⁺/K⁺-ATPase (NKA), as well as concentrations of SA and -SH in old-aged rats. The aging-induced impairment of the activities of membrane-bound ATPases and the changed levels of redox biomarkers were shown to be effectively restored by ACA treatment.

Abnormal remodeling of collagen and extracellular matrix caused by the accumulation of senescent fibroblasts in the dermis is the most likely cause of skin aging. Therefore, the application of "senolysis," in which only senescent cells are cleared from the body, has a potential in the development of antiaging treatments for skin. However, markers that label senescent fibroblasts only reflect the state of senescence, and it is important to develop markers as therapeutic targets to aid senolysis application. We investigated the potential of serotonin 2A receptor (HTR2A), which is involved in melanin production in response to ultraviolet light, as a senescent cell marker. The results showed that HTR2A is upregulated in aging dermal fibroblasts but is expressed at low levels in proliferating young cells. Flow cytometry demonstrated the presence of many HTR2A-positive cells in the aging cell population and few in the young cells. Furthermore, antibody-dependent cytotoxicity assays revealed that HTR2A preferentially sensitizes senescent fibroblasts and specifically damages only senescent cells by natural killer cells that recognize it. In conclusion, selective labeling of the novel senescent cell marker, HTR2A, could preferentially eliminate senescent cells and may contribute to the future development of novel skin senolysis approaches.