Systemic aging and aging‐related diseases DOI Open Access
Qiao Li,

Nanyin Xiao,

Heng Zhang

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(5)

Published: March 1, 2025

Abstract Aging is a biological process along with systemic and multiple organ dysfunction. It more recognized that aging disease instead of single‐organ functional disorder. Systemic plays profound role in diseases including neurodegenerative diseases, cardiovascular malignant diseases. Aged organs communicate other accelerate aging. Skeletal muscle, heart, bone marrow, skin, liver each through organ–organ crosstalk. The crosstalk can be mediated by metabolites lipids, glucose, short‐chain fatty acids (SCFA), inflammatory cytokines, exosomes. Metabolic disorders hyperglycemia, hyperinsulinemia, hypercholesterolemia caused chronic hallmarks leads to the destruction hemostasis, causes release senescence‐associated secretory phenotype (SASP), imbalance microbiota composition. Released factors further aggregate senescence, which promotes solid organs. Targeting senescence or delaying emerging as critical health strategy for solving age‐related especially old population. In current review, we will delineate mechanisms provide therapeutic targets

Language: Английский

The senescence-associated secretory phenotype and its physiological and pathological implications DOI
Boshi Wang, Jin Han, Jennifer H. Elisseeff

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(12), P. 958 - 978

Published: April 23, 2024

Language: Английский

Citations

152
The role of lipid metabolism in osteoporosis: Clinical implication and cellular mechanism DOI Creative Commons
Jing Zhang, Wenhui Hu, Zhiyong Zou

et al.

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(4), P. 101122 - 101122

Published: Sept. 21, 2023

In recent years, researchers have become focused on the relationship between lipids and bone metabolism balance. Moreover, many diseases related to lipid disorders, such as nonalcoholic fatty liver disease, atherosclerosis, obesity, menopause, are associated with osteoporotic phenotypes. It has been clinically observed in humans that these disorders promote changes osteoporosis-related indicators mineral density mass. Furthermore, similar phenotype were high-fat high-cholesterol-induced animal models. Abnormal (such increased oxidized elevated plasma cholesterol) affects microenvironment homeostasis via cross-organ communication, promoting differentiation of mesenchymal stem cells adipocytes, inhibiting commitment towards osteoblasts. disturbances affect balance by secretion cytokines receptor activator nuclear factor-kappa B ligand osteoblasts stimulating osteoclasts. Conclusively, this review addresses possible link osteoporosis elucidates potential modulatory mechanisms signaling pathways which We also summarize approaches prospects intervening for treatment.

Language: Английский

Citations

23
Inflammatory Processes Affecting Bone Health and Repair DOI
Haydée Torres de Oliveira, Katherine M. Arnold,

Manuela Oviedo

et al.

Current Osteoporosis Reports, Journal Year: 2023, Volume and Issue: 21(6), P. 842 - 853

Published: Sept. 28, 2023

Language: Английский

Citations

23
Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence DOI Creative Commons
Jing Hou, Kaixuan Chen,

Chen He

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(11), P. 1562 - 1581

Published: Sept. 12, 2024

The accumulation and systemic propagation of senescent cells contributes to physiological aging age-related pathology. However, which cell types are most susceptible the aged milieu could be responsible for senescence has remained unclear. Here we found that physiologically bone marrow monocytes/macrophages (BMMs) propagate multiple tissues, through extracellular vesicles (EVs), drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target microRNAs within BMM-EVs regulates downstream effects on dysfunction. Demonstrating therapeutic potential, report treatment with PPARα agonist fenofibrate effectively restores tissue homeostasis Suggesting conservation humans, cohort study 7,986 participants, use is associated reduced risk chronic disease higher life expectancy. Together, our findings establish BMMs can distant tissues cause dysfunction, they provide supportive evidence extend healthy lifespan.

Language: Английский

Citations

15
Ageing-related bone and immunity changes: insights into the complex interplay between the skeleton and the immune system DOI Creative Commons
Bobin Mi, Yuan Xiong, Samuel Knoedler

et al.

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Aug. 5, 2024

Abstract Ageing as a natural irreversible process inherently results in the functional deterioration of numerous organ systems and tissues, including skeletal immune systems. Recent studies have elucidated intricate bidirectional interactions between these two In this review, we provide comprehensive synthesis molecular mechanisms cell ageing. We further discuss how age-related changes influence system consequent impact alterations on system. Finally, highlight clinical implications findings propose potential strategies to promote healthy ageing reduce pathologic both

Language: Английский

Citations

13
Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing DOI Creative Commons

Nan-Yu Zou,

Ran Liu, Mei Huang

et al.

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 25, 2024

Abstract Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes SSPC remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during which triggers and impairs fracture healing. Local injection human rGCA young mice induced delayed repair. Genetic deletion Gca monocytes/macrophages was sufficient to rejuvenate repair aged alleviate senescence. Mechanistically, GCA binds plexin-B2 receptor activates Arg2-mediated mitochondrial dysfunction, resulting cellular Depletion Plxnb2 SSPCs impaired Administration GCA-neutralizing antibody enhanced healing mice. Thus, our study senescent within trigger secondary senescence, neutralization represents promising therapy for nonunion or union elderly individuals.

Language: Английский

Citations

10
Tau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss DOI Creative Commons
Wenyu Fu, Meng Chen, Kaidi Wang

et al.

Cell Research, Journal Year: 2025, Volume and Issue: 35(1), P. 23 - 44

Published: Jan. 2, 2025

Abstract Glucocorticoids (GCs) are the most prescribed anti-inflammatory and immunosuppressive drugs. However, their use is often limited by substantial side effects, such as GC-induced osteoporosis (GIO) with underlying mechanisms still not fully understood. In this study, we identify Tau a low-affinity binding receptor for GCs that plays crucial role in GIO. deficiency largely abolished bone loss induced high-dose dexamethasone, synthetic GC, both inflammatory arthritis GIO models. Furthermore, TRx0237, inhibitor identified from an FDA-approved drug library, effectively prevented Notably, combinatorial administration of TRx0237 dexamethasone completely overcame adverse effect treating arthritis. These findings present previously unrecognized GC low affinity, provide potential strategies to mitigate spectrum GC-related particularly osteoporosis.

Language: Английский

Citations

1
Bone-derived PDGF-BB drives brain vascular calcification in male mice DOI Creative Commons
Jiekang Wang,

Ching‐Lien Fang,

Kathleen Noller

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(23)

Published: Oct. 10, 2023

Brain vascular calcification is a prevalent age-related condition often accompanying neurodegenerative and neuroinflammatory diseases. The pathogenesis of large-vessel calcifications in peripheral tissue well studied, but microvascular the brain remains poorly understood. Here, we report that elevated platelet-derived growth factor BB (PDGF-BB) from bone preosteoclasts contributed to cerebrovascular male mice. Aged mice had higher serum PDGF-BB levels incidence compared with young mice, mainly thalamus. Transgenic preosteoclast-specific Pdgfb overexpression exhibited recapitulated age-associated thalamic calcification. Conversely, deletion displayed diminished In an ex vivo cerebral culture system, dose-dependently promoted Analysis osteogenic gene array single-cell RNA-Seq (scRNA-Seq) revealed upregulated multiple differentiation genes phosphate transporter Slc20a1 microvessels. Mechanistically, stimulated phosphorylation its receptor PDGFRβ (p-PDGFRβ) ERK (p-ERK), leading activation RUNX2. This activation, turn, induced transcription osteoblast PCs astrocytes. Thus, bone-derived by activating p-PDGFRβ/p-ERK/RUNX2 signaling cascade cells.

Language: Английский

Citations

22
“Bone-SASP” in Skeletal Aging DOI Creative Commons

Ching‐Lien Fang,

Bin Liu, Mei Wan

et al.

Calcified Tissue International, Journal Year: 2023, Volume and Issue: 113(1), P. 68 - 82

Published: May 31, 2023

Abstract Senescence is a complex cell state characterized by stable cycle arrest and unique secretory pattern known as the senescence-associated phenotype (SASP). The SASP factors, which are heterogeneous tissue specific, normally include chemokines, cytokines, growth adhesion molecules, lipid components that can lead to multiple age-associated disorders eliciting local systemic consequences. skeleton highly dynamic organ changes constantly in shape composition. Senescent cells bone marrow produce diverse factors induce alterations of through paracrine effects. Herein, we refer cell-associated “bone-SASP.” In this review, describe current knowledge cellular senescence SASP, focusing on role senescent mediating pathologies during natural aging premature syndromes. We also summarize bone-SASP glucocorticoids-induced damage. addition, discuss development osteoarthritis, highlighting mechanisms drives subchondral metabolic syndrome-associated osteoarthritis.

Language: Английский

Citations

19
Cross-talk of inflammation and cellular senescence: a new insight into the occurrence and progression of osteoarthritis DOI Creative Commons
Zeyu Han, Ketao Wang, Shenglong Ding

et al.

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Dec. 3, 2024

Abstract Osteoarthritis (OA) poses a significant challenge in orthopedics. Inflammatory pathways are regarded as central mechanisms the onset and progression of OA. Growing evidence suggests that senescence acts mediator inflammation-induced Given lack effective treatments for OA, there is an urgent need clearer understanding its pathogenesis. In this review, we systematically summarize cross-talk between cellular inflammation We begin by focusing on hallmarks senescence, summarizing supports relationship inflammation. then discuss interaction inflammation, including senescence-associated secretory phenotypes (SASP) effects pro- anti-inflammatory interventions senescence. Additionally, focus various types cartilage, subchondral bone, synovium, infrapatellar fat pad, stem cells, immune elucidating their impacts Finally, highlight potential therapies targeting senescent cells OA strategy promoting cartilage regeneration.

Language: Английский

Citations

8