scholarly journals Age-related increase in matrix stiffness downregulates α-Klotho in chondrocytes and induces cartilage degeneration

2021 ◽  
Author(s):  
Hirotaka Iijima ◽  
Gabrielle Gilmer ◽  
Kai Wang ◽  
Allison Bean ◽  
Yuchen He ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cartilage Degeneration ◽  
Akt Signaling ◽  
Cartilage Tissue ◽  
Matrix Stiffness ◽  
Knee Cartilage ◽  
Human Knee ◽  
Age Related ◽  
Insight Into ◽  
Upstream Regulators

ABSTRACTEnhanced mechanistic insight into age-related knee osteoarthritis (KOA) is an essential step to promote successful translation of animal research to bedside interventions. To this end, the goal of these studies was to interrogate molecular mechanisms driving age-related KOA in a mouse model and correspond findings to human knee cartilage. Unbiased mass spectrometry proteomics of cartilage tissue revealed PI3K/Akt signaling was the predominant pathway disrupted over time in male, but not female, mice. This finding was consistent with a significantly accelerated KOA progression in males when compared to female counterparts. In probing for upstream regulators of these age-dependent alterations, we found that α-Klotho, a suppressor of PI3K/Akt signaling and potent longevity protein, significantly decreased with aging in both mouse and human knee cartilage. Upstream of these alterations, we found that age-related increases in matrix stiffness initiated a cascade of altered nuclear morphology and downregulated α-Klotho expression, ultimately impairing chondrocyte health. Conversely, reducing matrix stiffness increased α-Klotho expression in chondrocytes, thus enhancing their chondrogencity and cartilage integrity. Collectively, our findings establish a novel mechanistic link between age-related alterations in ECM biophysical properties and regulation of cartilage health by α-Klotho.

scholarly journals MECHANISMS OF BRAIN REJUVENATION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S587-S587
Author(s):  
Saul Villeda
Keyword(s):  
Molecular Mechanisms ◽  
Aging Brain ◽  
Aging Effects ◽  
Effective Strategies ◽  
Mechanistic Insight ◽  
Age Related ◽  
Age Dependent ◽  
Cognitive Faculties ◽  
Insight Into ◽  
Aging Factors

Abstract A growing body of work has shown that systemic manipulations, such as heterochronic parabiosis and young blood administration, can partially reverse age-related cellular impairments and loss of cognitive faculties in the aged brain. These studies have revealed an age-dependent bi-directionality in the influence of the systemic environment indicating anti-aging factors in young blood elicit rejuvenation while pro-aging factors in old blood drive aging. It has been proposed that introducing anti-aging factors or mitigating the effect of pro-aging factors may provide effective strategies to rejuvenate aging phenotypes. Despite this potential, much is unknown as to the systemic and molecular mechanisms regulating anti-aging and pro-aging effects of blood-borne factors. I will discuss work from my research group that begins to provide mechanistic insight into the systemic and molecular drivers promoting rejuvenation in the aging brain.

scholarly journals Biological Properties and Pathological Stages of Chondrocyte Colony-Like Clusters in Human Osteoarthritic Cartilage Tissue

2020 ◽  
Author(s):  
XIAOJIAN WANG ◽  
LEI WEI ◽  
XIAOCHUN WEI ◽  
YAN XUE ◽  
ZHIQIANG ZHANG ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Cluster Formation ◽  
Cartilage Degeneration ◽  
Biological Properties ◽  
Cartilage Tissue ◽  
Osteoarthritic Cartilage ◽  
Human Knee ◽  
Knee Oa ◽  
Pathological Stages ◽  
Degenerative Cartilage

Abstract During the development of knee osteoarthritis(OA), chondrocyte colony-like clusters occur in cartilage tissue. However, the significance of chondrocyte colony-like cluster formation in cartilage tissue remains unclear. In these studies,we investigated the timing and location of chondrocyte colony-like clusters in cartilage tissue during the development of human knee OA,and explored the biological properties of chondrocytes in colony-like clusters and their significance for degenerative cartilage tissue. The resulte showed that chondrocyte colony-like clusters mainly formed in the OARSI grades 3 and 4 cartilage tissue,which could divide into four stages according to the quantity and biological properties of the chondrocytes inside the cluster.The chondrocyte colony-like clusters in cartilage tissue could cause the cartilage tissue to become looser and more porous, with more severe cartilage degeneration. To understand this, we further clarified the development of this disease and provided a new direction for the treatment of knee OA.

scholarly journals Comparative Proteomic Analysis of Young and Adult Bull (Bos taurus) Cryopreserved Semen

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2013
Author(s):  
Błażej Westfalewicz ◽  
Mariola Słowińska ◽  
Sylwia Judycka ◽  
Andrzej Ciereszko ◽  
Mariola A. Dietrich
Keyword(s):  
Proteomic Analysis ◽  
Molecular Mechanisms ◽  
Bos Taurus ◽  
Semen Quality ◽  
Age Related ◽  
Cryopreserved Sperm ◽  
Casa System ◽  
Insight Into ◽  
Sperm Movement

The age of the bull is widely accepted to influence the production of sperm, affecting the amount and quality of produced semen, which in turn impacts the results of cryopreservation. However, the exact influence of the maturation process on cryopreserved sperm, as well as the underlying molecular mechanisms of this process, are not fully understood. The goal of this study was to evaluate changes in the proteome of thawed semen (spermatozoa and supernatant) collected from young and adult bulls (n = 6) using the 2D-DIGE approach. The quality of semen was assessed using a CASA system and flow cytometry. We found no significant age-related variation in semen quality, with the exception of the average path velocity of sperm movement, which was higher in adult bulls. Proteomic analysis indicated 15 spermatozoa proteins and 10 supernatant proteins with significant age-related changes. Our results suggest that semen from adult bulls is better equipped with proteins related to energy production, protection of spermatozoa against oxidative stress and fertilizing ability. Proteins increased in abundance in young bull spermatozoa were connected to the cytoskeleton and its development, which strongly suggests that developmental processes are still in progress. In conclusion, our results provide novel insight into the mechanism of the development of the male reproductive system of cattle.

scholarly journals Biological Properties and Pathological Stages of Chondrocyte Colony-like Clusters in Osteoarthritic Cartilage Tissue

2020 ◽  
Author(s):  
XIAOJIAN WANG ◽  
Lei Wei ◽  
Xiaochun Wei ◽  
Yan Xue ◽  
Changqi Sun ◽  
...  
Keyword(s):  
Cartilage Degeneration ◽  
Research Society ◽  
Biological Properties ◽  
Cartilage Tissue ◽  
Osteoarthritic Cartilage ◽  
Human Knee ◽  
Osteoarthritis Research Society ◽  
Grade 3 ◽  
Pathological Stages ◽  
Hypertrophic Changes

Abstract Objective:In these studies,we investigated the timing and location of chondrocyte colony-like clusters in cartilage tissue during the development of human knee osteoarthritis(OA),and explored the biological properties of chondrocytes in colony-like clusters and their significance for degenerative cartilage tissue.Methods:Osteoarthritis Research Society International (OARSI) grade 0～6 cartilage tissue was obtained from the human tibial plateau, and histologicalsections were made to observe whether there were chondrocyte colony-like clusters in the cartilage tissue and where they occurred. Immunohistochemistry, PCR and western blotting were used to detect the biological properties of chondrocytes in the colony-like clusters and to describe the histopathological stages of the colony-like clusters according to the properties of thechondrocytes in the cluster.Results: There were a large number of chondrocyte colony-like clusters in the middle zone of OARSI grade 3 and grade 4 cartilage tissue.The chondrocytes in the colony-like clusters rapidly proliferated from one to a certain number and then rapidly underwent hypertrophic changes,synthesizing and releasing the MMP-13 protein to degrade cartilage tissue and enlarge chondrocyte lacunae.Eventually, the chondrocytes in the colony-like cluster underwent apoptosis and disappeared, leaving large empty chondrocyte lacunae.According to this process, chondrocyte colony-like clusters could be divided into four stages.Conclusions: Chondrocyte colony-like clusters mainly formed during the development of OA of OARSI grades 3 and 4 could cause the cartilage tissue to become looser and more porous, with more severe cartilage degeneration.

scholarly journals Local Anesthetic Lidocaine and Cancer: Insight Into Tumor Progression and Recurrence

2021 ◽  
Vol 11 ◽  
Author(s):  
Caihui Zhang ◽  
Cuiyu Xie ◽  
Yao Lu
Keyword(s):  
Pain Relief ◽  
Signaling Pathways ◽  
Local Anesthetic ◽  
Immune Regulation ◽  
Molecular Mechanisms ◽  
Primary Treatment ◽  
Akt Signaling ◽  
Clinical Benefits ◽  
Insight Into ◽  
Anti Inflammation

Cancer is a leading contributor to deaths worldwide. Surgery is the primary treatment for resectable cancers. Nonetheless, it also results in inflammatory response, angiogenesis, and stimulated metastasis. Local anesthetic lidocaine can directly and indirectly effect different cancers. The direct mechanisms are inhibiting proliferation and inducing apoptosis via regulating PI3K/AKT/mTOR and caspase-dependent Bax/Bcl2 signaling pathways or repressing cytoskeleton formation. Repression invasion, migration, and angiogenesis through influencing the activation of TNFα-dependent, Src-induced AKT/NO/ICAM and VEGF/PI3K/AKT signaling pathways. Moreover, the indirect influences are immune regulation, anti-inflammation, and postoperative pain relief. This review summarizes the latest evidence that revealed potential clinical benefits of lidocaine in cancer treatment to explore the probable molecular mechanisms and the appropriate dose.

scholarly journals A Regulatory Network for miR156-SPL Module in Arabidopsis thaliana

2019 ◽  
Vol 20 (24) ◽  
pp. 6166 ◽  
Author(s):  
Chenfei Zheng ◽  
Meixia Ye ◽  
Mengmeng Sang ◽  
Rongling Wu
Keyword(s):  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Phase Changes ◽  
Plant Age ◽  
Age Related ◽  
Complex Process ◽  
Spl Genes ◽  
Regulation Network ◽  
Rich Data ◽  
Insight Into

Vegetative phase changes in plants describes the transition between juvenile and adult phases of vegetative growth before flowering. It is one of the most fundamental mechanisms for plants to sense developmental signals, presenting a complex process involving many still-unknown determinants. Several studies in annual and perennial plants have identified the conservative roles of miR156 and its targets, SBP/SPL genes, in guiding the switch of plant growth from juvenile to adult phases. Here, we review recent progress in understanding the regulation of miR156 expression and how miR156-SPLs mediated plant age affect other processes in Arabidopsis. Powerful high-throughput sequencing techniques have provided rich data to systematically study the regulatory mechanisms of miR156 regulation network. From this data, we draw an expanded miR156-regulated network that links plant developmental transition and other fundamental biological processes, gaining novel and broad insight into the molecular mechanisms of plant-age-related processes in Arabidopsis.

scholarly journals SYSTEMIC MECHANISMS OF BRAIN REJUVENATION

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 198-198
Author(s):  
Saul Villeda
Keyword(s):  
Molecular Mechanisms ◽  
Circulatory System ◽  
Adult Brain ◽  
Aging Brain ◽  
Aging Effects ◽  
Mechanistic Insight ◽  
Age Related ◽  
The Brain ◽  
Insight Into ◽  
Aging Factors

Abstract Aging drives cellular and cognitive impairments in the adult brain. It is imperative to gain mechanistic insight into what drives aging phenotypes in the brain in order to maintain, and even restore, functional integrity in the elderly. We, and others, have shown that systemic manipulations - such as heterochronic parabiosis (in which a young and old circulatory system are joined) and administration of young blood or exercise induced blood factors - can reverse age-related impairments in regenerative, synaptic and inflammatory processes, as well as rescue cognitive faculties in the aged brain. These studies have revealed an age-dependent bi-directionality in the influence of the systemic environment indicating pro-youthful factors in young blood elicit rejuvenation while pro-aging factors in old blood drive aging. It has been proposed that introducing pro-youthful factors or mitigating the effect of pro-aging factors may provide effective strategies to rejuvenate aging phenotypes in the brain. Despite this potential, much is unknown as to the systemic and molecular mechanisms regulating pro-youthful and pro-aging effects of blood-borne factors. I will discuss work from my research group that begins to provide mechanistic insight into the systemic and molecular drivers promoting rejuvenation in the aging brain.

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

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