Regulation of aged skeletal muscle regeneration by circulating extracellular vesicles

Synergistic Anti-Ageing through Senescent Cells Specific Reprogramming

“…It is shown that blood therapy involves several different anti-ageing factors (GDF11 [ 20 ], GPLD1 [ 21 ], clusterin [ 22 ], Klotho [ 23 ], etc.). On the one hand, it leads to controversy [ 19 ], but on the other hand, it also suggests that greater benefits may be achieved by synchronizing multiple factors to combat ageing.…”

“…The youthful secretory phenotype is a newly proposed hypothesis. It aims to generalize the anti-ageing factors (including GDF11, GPLD1, clusterin, Klotho, NAD + , eNAMPT, GSTM2, exosomes, et al) found in young blood and in the secretome of young cells [ 20 , 21 , 22 , 23 , 49 , 51 , 57 ]. These “young factors (existing in young blood as well as being secreted by a heterogeneous subgroup of ageing cells)” may dilute or inhibit “old factors” promoting ageing, thus playing a rejuvenating role [ 14 , 15 ].…”

Orally-active, clinically-translatable senolytics restore α-Klotho in mice and humans

“…Mice overexpressing α-Klotho have increased lifespan, enhanced cognition, delayed age-related vascular dysfunction, decreased diabetes-related inflammation, and improved skeletal muscle regeneration. 27 , 28 , 29 As α-Klotho holds therapeutic potential, various strategies to increase α-Klotho have been proposed. However, despite extensive effort there are few approaches for increasing or restoring α-Klotho that are either feasible to advance into clinical trials or that have shown efficacy in trials.…”

Extracellular Vesicles and Resistance to Anticancer Drugs: A Tumor Skeleton Key for Unhinging Chemotherapies

“…EVs orchestrate physiological regulation in all tissues. The involvement of EVs is reported in many physiological processes such as angiogenesis [i.e., via the shedding of EV-encapsulated angiogenetic factors such as tetraspanin8, L-selectin, vascular endothelium growth factor receptor 1 (VEGFR1), and CD147], liver function and metabolism (i.e., asialoglycoprotein receptor-, apolipoprotein E/AV-and glutathione S-transferase-enriched EVs), bone resorption (i.e., pro-osteoclastogenic RANKL-positive EVs from osteoblasts), cornea wounding (i.e., fibronectinand thrombospondin 1-enriched EVs from corneal epithelial cells), lung cell differentiation (i.e., EV-mediated shuttling and de novo transcription of pulmonary epithelial cell mRNAs), muscle regeneration (i.e., shuttling of a-Klotho transcript inducing muscle rejuvenating), bowel barrier integrity (epithelial cellderived EVs alleviate gut injury after intestinal ischemia/ reperfusion by miR-23a-3p), gut microbiota (Escherichia coli Nissle 1917 release vesicles positively modulates the intestinal epithelial barrier through upregulation zonulin-1/-2 and claudin-14), and immunity (macrophage-derived EVs contains alarmins orchestrating immune regulation) (16)(17)(18)(19)(20)(21)(22)(23)(24). Similarly, tissue dysfunctions and diseases are sustained by EV exchange including but not limited to stroke, obesity, skeletal muscle atrophy, colitis, and major depressive disorder (25)(26)(27)(28)(29)(30)(31)(32).…”