Treatment Of Age-related Diseases Research Articles

Nanoparticle-Protein Corona-Based Tissue Proteomics for the Aging Mouse Proteome Atlas.

Highly abundant proteins present in biological fluids and tissues significantly interfere with low-abundance protein identification by mass spectrometry (MS), limiting proteomic depth and hindering protein biomarker discovery. Herein, to enhance the coverage of tissue proteomics, we developed a nanoparticle-protein corona (NP-PC)-based method for the aging mouse proteome atlas. Based on this method, we investigated the complexity of life process of 5 major organs, including the heart, liver, spleen, lungs, and kidneys, from 4 groups of mice at different ages. Compared with the conventional strategy, NP-PC-based proteomics significantly increased the number of identified protein groups in the heart (from 3007 to 3927; increase of 30.6%), liver (from 2982 to 4610; increase of 54.6%), spleen (from 5047 to 7351; increase of 45.7%), lungs (from 4984 to 6903; increase of 38.5%), and kidneys (from 3550 to 5739; increase of 61.7%), and we identified a total of 10 104 protein groups. The overall data indicated that 3-week-old mice showed more differences compared with the other three age groups. The proteins of amino acid-related metabolism were increased in aged mice compared with those in the 3-week-old mice. Protein-related infections were increased in the spleen of the aged mice. Interestingly, the spliceosome-related pathway significantly changed from youth to elders in the liver, spleen, and lungs, indicating the vital role of the spliceosome during the aging process. Our established aging mouse organ proteome atlas provides comprehensive insights into understanding the aging process, and it may help in prevention and treatment of age-related diseases.

Drug Delivery Strategies for Age-Related Diseases.

Drug delivery systems (DDSs) enable the controlled release of drugs in the body. DDSs have attracted increasing attention for the treatment of various disorders, including cancer, inflammatory diseases, and age-related diseases. With recent advancements in our understanding of the molecular mechanisms of aging, new target molecules and drug delivery carriers for age-related diseases have been reported. In this review, we will summarize the recent research on DDSs for age-related diseases and identify DDS strategies in the treatment of age-related diseases.

Exosomes derived from hTERT-immortalized cells delay cellular senescence of human fibroblasts

hTERT gene therapies hold significant promise for treating age-related diseases. However, further research is required to address the challenges of delivery and ethical considerations. We hypothesized that exosomes derived from hTERT-immortalized cells could function similarly to hTERT gene therapies by maintaining telomere length and attenuating cellular senescence biomarkers. In this study, we overexpressed the hTERT gene in Human Foreskin Fibroblast-1 cells (HFF cells) to produce hTERT-immortalized HFF cells (hT-HFF cells). We then used exosomes derived from these hT-HFF cells to treat human fibroblasts, HFF cells. Our results demonstrated that these exosomes effectively attenuated biomarkers of cellular senescence in HFF cells. Furthermore, analysis revealed that hTERT mRNA was indeed packaged into the exosomes from hT-HFF cells. This mRNA was capable of elongating telomeres and delaying cellular senescence in HFF cells. Therefore, exosomes from hT-HFF cells show potential as a treatment for age-related diseases.

Fructosyl Amino Oxidase as a Therapeutic Enzyme in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is an age-related disorder that is a global public health problem. The non-enzymatic Maillard reaction results in the formation of advanced glycation end products (AGEs). Accumulation of AGEs in drusen plays a key role in AMD. AGE-reducing drugs may contribute to the prevention and treatment of AGE-related disease. Fructosamine oxidase (FAOD) acts on fructosyl lysine and fructosyl valine. Based upon the published results of fructosamine 3-kinase (FN3K) and FAOD obtained in cataract and presbyopia, we studied ex vivo FAOD treatment as a non-invasive AMD therapy. On glycolaldehyde-treated porcine retinas, FAOD significantly reduced AGE autofluorescence (p = 0.001). FAOD treatment results in a breakdown of AGEs, as evidenced using UV fluorescence, near-infrared microspectroscopy on stained tissue sections of human retina, and gel permeation chromatography. Drusen are accumulations of AGEs that build up between Bruch's membrane and the retinal pigment epithelium. On microscopy slides of human retina affected by AMD, a significant reduction in drusen surface to 45 ± 21% was observed following FAOD treatment. Enzymatic digestion followed by mass spectrometry of fructose- and glucose-based AGEs (produced in vitro) revealed a broader spectrum of substrates for FAOD, as compared to FN3K, including the following: fructosyllysine, carboxymethyllysine, carboxyethyllysine, and imidazolone. In contrast to FN3K digestion, agmatine (4-aminobutyl-guanidine) was formed following FAOD treatment in vitro. The present study highlights the therapeutic potential of FAOD in AMD by repairing glycation-induced damage.

Emerging insights into cuproptosis and copper metabolism: implications for age-related diseases and potential therapeutic strategies.

The expanding geriatric population, whose predisposition toward disabling morbidities and age-related diseases (ARD) is well-documented, has become a paramount social issue, exerting an onerous burden on both the healthcare industry and wider society. ARD manifest as the progressive deterioration of bodily tissues and organs, eventually resulting in the failure of these vital components. At present, no efficacious measures exist to hinder the onset of ARD. Copper, an essential trace element, is involved in a wide range of physiological processes across different cell types. In recent research, a novel variant of copper-dependent cell death, termed cuproptosis, has been identified. This mode of cellular demise stands apart from previously recognized types of cell death. Cuproptosis occurs when copper binds with acyl-CoA synthetase in the tricarboxylic acid (TCA) cycle, resulting in protein aggregation and protein toxicity stress, ultimately leading to cell death. In this paper, we provide a concise overview of the current understanding concerning the metabolism of copper, copper-related diseases, the hallmarks of copper toxicity, and the mechanisms that regulate copper toxicity. Additionally, we discuss the implications of cuproptosis mutations in the development of ARD, as well as the potential for targeting cuproptosis as a treatment for ARD.

Effect of quercetin on the protein-substrate interactions in SIRT6: Insight from MD simulations

SIRT6 is of interest for its promising effect in the treatment of aging-related diseases. Studies have shown quercetin (QUE) and its derivatives have varying degrees of effect on the catalytic effect of SIRT6. In the research, the effect of QUE on the protein-substrate interaction in the SIRT6-mediated mono-ADP ribosylation system was investigated by conventional molecular dynamics (MD) simulations combined with MM/PBSA binding free energy calculations. The results show that QUE can bind stably to SIRT6 with the binding energy of −22.8 kcal/mol and further affect the atomic interaction between SIRT6 and NAD+ (or H3K9), resulting in an increased affinity between SIRT6-NAD+ and decreased SIRT6-H3K9 binding capacity. At the same time, the binding of QUE can also alter some structural characteristics of the protein, with large shifts occurring in the residue regions involving the N-terminal (residues 1–27), Rossmann fold regions (residues 55–92), and ZBD (residues 164–179). Thus, QUE shows great potential as a scaffold for the design of novel potent SIRT6 modulators.

Sirtuins in clinical trials of approaches to the treatment of neurodegenerative diseases

Progressive decline in physiological functions during aging leads to various diseases that place a heavy burden on patients, their families and society as a whole. Due to the increasing average life expectancy, the problems of prevention and treatment of age-related diseases are becoming more and more relevant. As part of the research on the regulation of the aging program, considerable attention has been focused on a small family of NAD+-dependent deacetylases and deacylases called sirtuins. These proteins are involved in the regulation of numerous intracellular processes, and disruption of their functions plays an important role in the development of various diseases, such as metabolic disorders, pathologies of the cardiovascular system and other organs, musculoskeletal diseases, and neurodegeneration. It is interesting to note that the activity of sirtuins can be modulated to some extent under the influence of pharmacological agents, which makes them promising targets for age-related diseases prevention and therapy. The presented review will describe the influence of sirtuins on the development and pathogenesis of neurodegenerative diseases, as well as discuss recorded clinical trials focused on its therapy with pharmacological agents potentially affecting the activity of sirtuin proteins.

The function of Bazhen decoction in rescuing progeroid cell senescence via facilitating G-quadruplex resolving and telomere elongation

Ethnopharmacological relevanceThe Bazhen decoction is one of the most extensively used Traditional Chinese medicine (TCM) prescriptions for treatment of aging related diseases. However, due to the complexity of the components, the pharmacological mechanism of Bazhen decoction is still limited. Aim of the studyIn this study, with the aim of helping the clinical precision medicine of TCM, we try out a systematic analysis for dissecting the molecular mechanism of complicated TCM prescription: Bazhen decoction. We identify the pharmacological mechanism of Bazhen decoction in telomere elongation as revealed by systematic analysis. Materials and methodsBy RNA sequencing and transcriptome analysis of Bazhen decoction treated wild type cells, we reveal the transcriptome profile induced by Bazhen decoction. We utilized the cells derived from Werner syndrome (WS) mice, which is known to be dysfunctional in telomere elongation due to the deficiency of DNA helicase Wrn. By Western blot, qPCR, Immunofluorescence, flow cytometry, telomere FISH, and SA-β-Gal staining, we verify the transcriptome data and confirm the pharmacological function of Bazhen decoction and its drug containing serum in telomere elongation and reversing progeroid cell senescence. ResultsWe reveal that Bazhen decoction may systematically regulate multiple anti-aging pathways, including stem cell regulation, protein homeostasis, cardiovascular function, neuronal function, anti-inflammation, anti-DNA damage induced stress, DNA helicase activity and telomere lengthening. We find that Bazhen decoction and its drug containing serum could up-regulate multiple DNA helicases and telomere regulating proteins. The increased DNA helicases promote the resolving of G-quadruplex (G4) structures, and facilitate DNA replication and telomere elongation. These improvements also endow the cellular resistance to DNA damages induced by replication stress, and rescue the WS caused cellular senescence. ConclusionsTogether these data suggest that Bazhen decoction up-regulate the expression of DNA helicases, thus facilitate G4 resolving and telomere maintenance, which rescue the progeroid cellular senescence and contribute to its anti-aging properties. Our data reveal a new molecular mechanism of Bazhen decoction in anti-aging related diseases via elongating telomere, this may shed light in the application of Bazhen decoction in multiple degenerative diseases caused by telomere erosion.

Sensitive and Selective Dual-Mode Responses to Reactive Oxygen Species by Chiral Manganese Dioxide Nanoparticles for Antiaging Skin.

Excessive accumulation of reactive oxygen species (ROS) can lead to oxidative stress and oxidative damage, which is one of the important factors for aging and age-related diseases. Therefore, real-time monitoring and the moderate elimination of ROS is extremely important. In this study, a ROS-responsive circular dichroic (CD) at 553nm and magnetic resonance imaging (MRI) dual-signals chiral manganese oxide (MnO2 ) nanoparticles (NPs) are designed and synthesized. Both the CD and MRI signals show excellent linear ranges for intracellular hydrogen peroxide (H2 O2 ) concentrations, with limits of detection (LOD) of 0.0027nmol/106 cells and 0.016nmol/106 cells, respectively. The lower LOD achieved with CD detection may be attributable to its higher anti-interference capability from the intracellular matrix. Importantly, ROS-induced cell aging is intervened by chiral MnO2 NPs via redox reactions with excessive intracellular ROS. In vivo experiments confirm that chiral MnO2 NPs effectively eliminate ROS in skin tissue, reduce oxidative stress levels, and alleviate skin aging. This approach provides a new strategy for the diagnosis and treatment of age-related diseases.

Excessive apoptosis of Rip1-deficient T cells leads to premature aging.

In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T-cell changes and aging remains unclear. In this study, we find that T-cell-specific Rip1 KO mice show similar age-related T cell changes and exhibit signs of accelerated aging-like phenotypes, including inflammation, multiple age-related diseases, and a shorter lifespan. Mechanistically, Rip1-deficient Tcells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co-deletion of Fadd in Rip1-deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging-like phenotypes, and prolongs life span in T-cell-specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age-related diseases.

Molecular and cellular mechanisms of ageing: modern knowledge (literature review)

Ageing (as known as eldering, senescence) is a genetically and epigenetically programmed pathophysiological process. Velocity of biological ageing is defined as balance between alteration and reparation of body structures. According to last World Health Organization (WHO) highlights ageing still stays an extremely actual scientific, social and demographic problem: in 2020 total number of people older than 60 years and older was 1 billion people; in 2030 future number may be 1,4 billion people, in 2050 - 2,1 billion people. Absence of single universal theory of aging nowadays is reason for scientifical and clinical collaboration between biologists and doctors, including endocrinologists. Designing of potentially effective newest anti-ageing strategies (such as natural/synthetic telomerase regulators, mesenchymal stem cells etc.) is of interest to scientific community. The aim of present article is a review of modern omics (genomic, proteomic, metabolomic) ageing mechanisms, potential ways of targeted prevention and treatment of age-related disease according to conception of personalized medicine. Present review is narrative, it does not lead to systematic review, meta-analysis and does not aim to commercial advertisement. Review has been provided via PubMed article that have been published since 1979 until 2022.

Pharmacological activities and therapeutic potential of galangin, a promising natural flavone, in age-related diseases.

The extension of average life expectancy and the aggravation of population aging have become the inevitable trend of human development. In an aging society, various problems related to medical care for the elderly have become increasingly prominent. However, most of the age-related diseases have the characteristics of multiple diseases at the same time, prone to complications, and atypical clinical manifestations, which bring great difficulties to its treatment. Galangin (3,5,7-trihydroxyflavone) is a natural active compound extracted from the root of Alpinia officinarum Hance (Zingiberaceae). Recently, many studies have shown that galangin has potential advantages in the treatment of neurodegenerative diseases and cardiovascular and cerebrovascular diseases, which are common in the elderly. In addition, it also showed that galangin had prospective activities in the treatment of tumor, diabetes, liver injury, asthma and arthritis. This review aims to systematically summarize and discuss the effects and the underlying mechanism of galangin in the treatment of age-related diseases. We searched PubMed, SciFinder, Web of Science and CNKI literature database resources, combined with the keywords "galangin", "neurodegenerative disease", "tumor", "diabetes", "pharmacological activity", "drug combination", "pharmacokinetics", "drug delivery system" and "safety", and comprehensively reviewed the pharmacological activities and mechanism of galangin in treating age-related diseases. According to the previous studies on galangin, the anti-neurodegenerative activity, cardiovascular and cerebrovascular protective activity, anti-tumor activity, anti-diabetes activity, anti-arthritis activity, hepatoprotective activity and antiasthmatic activity of galangin were discussed, and the related mechanisms were classified and summarized in detail. In addition, the drug combination, pharmacokinetics, drug delivery system and safety of galangin were furtherly discussed. This review will provide reference for galangin in the treatment of age-related diseases. Meanwhile, further experimental research and long-term clinical trials are needed to determine the therapeutic safety and efficacy of galangin.

Potential Roles of Exosomes in Aging and Age-Related Diseases

Objectives: To review exosomes in aging and age-associated diseases. Design: A review study. Participants: Aged animals. Interventions: Exosome treatment. Outcome measures: The occurrence of age-associated diseases, aging skin, cognition, and cardiac dysfunction. Results: Exosomes are secreted by various cell types and comprise proteins, lipids, functional messenger RNAs, cytokines, growth factors, different noncoding RNA, micro-RNAs, and other bioactive substances. These nanoparticles are implicated in several physiological processes, including intercellular communication, cell migration, angiogenesis, and anti-tumor immunity, and have gained major interest in regenerative medicine. Furthermore, several studies have demonstrated the potential roles of exosomes in age-associated diseases such as aging skin, cognition, Alzheimer’s disease (AD), Parkinson’s disease (PD), and osteoarthritis (OA). Conclusions: We summarized various mechanisms of exosomes in the treatment of age-related diseases, including OA, PD, AD, and aged skin. These vesicles can be of efficient medicinal value for aged-associated disease therapy in preclinical trials. Further clinical trials are needed, but the majority of the literature suggests research directions that may provide new treatment approaches and strategies for clinical application.

Thymus atlanticus: A Source of Nutrients with Numerous Health Benefits and Important Therapeutic Potential for Age-Related Diseases.

Thymus atlanticus (Lamiaceae) is a plant endemic to the Mediterranean basin that is found in significant quantities in the arid regions of Morocco. Thymus atlanticus is used in traditional medicine to treat infectious and non-infectious diseases. It is also used for the isolation of essential oils and for the seasoning of many dishes in the Mediterranean diet. The major constituents of Thymus atlanticus are saponins, flavonoids, tannins, alkaloids, various simple and hydroxycinnamic phenolic compounds, and terpene compounds. Several of these compounds act on signaling pathways of oxidative stress, inflammation, and blood sugar, which are parameters often dysregulated during aging. Due to its physiochemical characteristics and biological activities, Thymus atlanticus could be used for the prevention and/or treatment of age-related diseases. These different aspects are treated in the present review, and we focused on phytochemistry and major age-related diseases: dyslipidemia, cardiovascular diseases, and type 2 diabetes.

Core mechanism and therapeutic methods of aging revealed by qi-collateral theory in traditional Chinese medicine

Abstract Aging, a complex and multisystem process, has increasingly become a hot issue of global concern. Traditional Chinese medicine has accumulated rich understanding of aging during thousands of years of development, which provides valuable references for the in-depth study of overall aging. According to the qi-collateral theory in traditional Chinese medicine, essence is the origin of life; qi is the driving force of life; and spirit is the embodiment of life. This theory interprets key scientific issues such as the formation of life, the driving force of life, the function of zang-fu organs, and the spirit and consciousness. Furthermore, it reveals the key mechanism of aging. That is, the deficiency of kidney essence is the root of aging; the loss of vitality is the key of aging; and the depletion of body and spirit is the manifestation of aging. Based on the experience of medical practitioners in the past dynasties, such as nourishing essence, black food tonifying the kidney, and supplementing essence with flesh-blood products, the treatment method of invigorating kidney and supplementing essence, harmonizing yin and yang, reinforcing the vitality, and nourishing the body and spirit was proposed. Furthermore, an innovative Chinese patent medicine, Bazi Bushen capsules, is developed, which exerts the antiaging effect by replenishing qi, invigorating the spirit, and nourishing the body and spirit. Pharmacological and clinical studies have confirmed that this preparation has antiaging effects and are effective in the prevention and treatment of age-related diseases. Experimental studies have shown that Bazi Bushen capsules can delay the overall aging, reduce the DNA methylation and extend the healthy life of naturally aging mice, mitigate the age-related cognitive dysfunction, improve neurological function, maintain redox homeostasis and telomere integrity, and inhibit apoptosis. Moreover, Bazi Bushen capsules can increase the dermal thickness and the collagen fiber and elastic fiber content to prevent skin aging. In addition, Bazi Bushen capsules can correct the lipid metabolism disorders and ameliorate multisystem age-related diseases such as osteoporosis in surgically induced menopausal rats. This article discusses the pathogenesis, treatment, and prescription of aging and the antiaging theory, aiming to provide a basis for delaying aging and preventing related diseases.

Network pharmacology, molecular docking, and molecular dynamics simulation to elucidate the mechanism of anti-aging action of Tinospora cordifolia.

Scientific research has demonstrated that Tinospora cordifolia acts as an anti-aging agent in several experimental models, generating global interest in its underlying molecular mechanisms of this activity. The aim of the study was to identify the possible phytochemical compounds of T. cordifolia that might combat age-related illness through integrating network pharmacology, molecular docking techniques, and molecular dynamics (MD) study to explore their potential mechanisms of action. To carry out this study, several databases were used, including PubChem, KNApSAcK family database, PubMed, SwissADME, Molsoft, SwissTargetPrediction, GeneCards, and OMIM database. For network development and GO enrichment analysis KEGG, ShinyGo 0.77, and the STRING database were used. For better analysis, the networks were also constructed using Cytoscape 3.9.1. The Cytoscape network analyzer tool was used for data analysis, and molecular docking was done via Vina-GPU-2.0. The best compounds and AKT1 were finally subjected to MD simulation for 100ns. The CytoHubba plugin of Cytoscape identified ten key targets, commonly called hub genes, including AKT1, GAPDH, and TP53, and so on. GO and KEGG pathway enrichment analysis revealed the relevant biological processes, cellular components, and molecular functions involved in treating aging-related disorders. KEGG pathway analysis involved neuroactive ligand-receptor interactions, lipid and atherosclerosis, and cAMP signaling. The docking of 100 T. cordifolia compounds with AKT1 demonstrated good binding affinity, particularly for Amritoside, Sitagliptin, Berberine, and Piperine. Finally, the relative stability of four-hit phytochemicals was validated by MD simulation, which may be the most crucial compound for anti-aging activity. In conclusion, this study used network pharmacology, molecular docking, and MD simulation to identify the compounds in T. cordifolia and proposed a potential mechanism for anti-aging activity. These results suggest future directions for the prevention and treatment of age-related diseases.

Bone targeting miR-26a loaded exosome-mimetics for bone regeneration therapy by activating Wnt signaling pathway

Mesenchymal stem cell-derived exosomes (MSC-Exos) have shown great potential in the areas of bone regeneration and treatment of age-related diseases. Engineered exosomes can integrate multiple functional components to achieve optimal, targeted therapeutic effects. This study combined large-scale generation, bone-targeting modification, and miR-26a loading for exosome-mimetics (EMs) to construct a cell-free delivery system that promotes bone regeneration with good biocompatibility. EMs were fabricated through sequential extrusion of MSCs and reached a 15-fold production yield compared to conventional exosome secretion. Systemic injection of Asp8-EM/miR-26a in mouse models accelerated bone-defect healing and prevented osteoporosis. The underlying mechanism involves miR-26a targeting glycogen synthase kinase-3β (GSK-3β) to induce β-catenin accumulation, thus activating Wnt signaling pathway and promoting bone regeneration. This study provides a feasible and effective strategy for modifying EMs to enhance bone regeneration.

Mulberry leaves attenuate D-galactose-induced aging in vivo and in vitro.

Mulberry leaves contain many bioactive compounds and have been widely used in traditional medicines and functional foods for prevention and treatment of age-related diseases, such as diabetes, cognitive impairment and obesity-mediated liver cancer. Aging has an irreversible negative impact on human health for many years, even decades, before death, which is a social and economic burden on society. The objective of this study was to investigate the antioxidant and anti-aging effects of mulberry leaf extract (MLE) in vivo and in vitro. The Caenorhabditis elegans (C. elegans) was used as a model organism to observe the effects of different concentrations of MLE (1, 2, 4, 8 mg/mL) on nematodes' healthy lifespan, reproductive capacity, locomotion, stress resistance, and antioxidation. In addition, D-galactose (D-gal) induced liver aging in mice and L-02 cells were established. The antioxidant and anti-aging effects of MLE were evaluated by body weight, organ indexes, malondialdehyde (MDA), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), aspartate and alanine aminotransferases (AST and ALT), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), hematoxylin and eosin (H&E), senescence-associated β-galactosidase (SA-β-Gal). Besides, the expressions of AMPK/SIRT1/PGC-1α and Nrf2-Keap1 were detected by Western blotting. MLE could significantly prolonged nematodes' average life span and improved most physiological indicators related to aging of C. elegans. Moreover, Treatment with MLE ameliorated the decreased body weight and organ index (weight of organ/body weight) in model mice, and protected against oxidative stress in mice and liver cells, in a dose-dependent manner, up-regulating T-SOD and T-AOC, while reducing ROS and MDA levels. MLE decreased both liver and cell levels of AST and ALT, and enhanced the mitochondrial membrane potential. MLE activated the AMPK/SIRT1/PGC-1α pathways, participated in mitochondrial biosynthesis and oxidative metabolism and delayed D-gal-induced aging. MLE promoted the accumulation of Nrf2 in the nucleus, indicating that the improved oxidative stress response was mediated by the Nrf2-Keap1 pathway in vivo and in vitro. MLE appeared to have great potential for stimulating the oxidative stress response and attenuating the aging process of in vivo and in vitro, and provide a novel health-promoting resource against aging and aging-related diseases.

Mechanism of mesenchymal stem cells and exosomes in the treatment of age-related diseases.

Mesenchymal stem cells (MSCs) from multiple tissues have the capability of multidirectional differentiation and self-renewal. Many reports indicated that MSCs exert curative effects on a variety of age-related diseases through regeneration and repair of aging cells and organs. However, as research has progressed, it has become clear that it is the MSCs derived exosomes (MSC-Exos) that may have a real role to play, and that they can be modified to achieve better therapeutic results, making them even more advantageous than MSCs for treating disease. This review generalizes the biological characteristics of MSCs and exosomes and their mechanisms in treating age-related diseases, for example, MSCs and their exosomes can treat age-related diseases through mechanisms such as oxidative stress (OS), Wnt/β-catenin signaling pathway, mitogen-activated protein kinases (MAPK) signaling pathway, and so on. In addition, current in vivo and in vitro trials are described, and ongoing clinical trials are discussed, as well as the prospects and challenges for the future use of exosomes in disease treatment. This review will provide references for using exosomes to treat age-related diseases.

Cycloastragenol: A Novel Senolytic Agent That Induces Senescent Cell Apoptosis and Restores Physical Function in TBI-Aged Mice

Accumulating evidence indicates that the increased burden of senescent cells (SCs) in aged organisms plays an important role in many age-associated diseases. The pharmacological elimination of SCs with "senolytics" has been emerging as a new therapy for age-related diseases and extending the healthy lifespan. In the present study, we identified that cycloastragenol (CAG), a secondary metabolite isolated from Astragalus membrananceus, delays age-related symptoms in mice through its senolytic activity against SCs. By screening a series of compounds, we found that CAG selectively kills SCs by inducing SCs apoptosis and that this process is associated with the inhibition of Bcl-2 antiapoptotic family proteins and the PI3K/AKT/mTOR pathway. In addition, CAG treatment also suppressed the development of the senescence-associated secretory phenotype (SASP) in SCs, thereby inhibiting cell migration mediated by the SASP. Furthermore, the administration of CAG for 2 weeks to mice with irradiation-induced aging alleviated the burden of SCs and improved the animals' age-related physical dysfunction. Overall, our studies demonstrate that CAG is a novel senolytic agent with in vivo activity that has the potential to be used in the treatment of age-related diseases.