Roles of extracellular vesicles in the aging microenvironment and age‐related diseases

Abstract

Cellular senescence is a persistently hypoproliferative state with diverse stressors in a specific aging microenvironment. Senescent cells have a double-edged sword effect: they can be physiologically beneficial for tissue repair, organ growth, and body homeostasis, and they can be pathologically harmful in age-related diseases. Among the hallmarks of senescence, the SASP, especially SASP-related extracellular vesicle (EV) signalling, plays the leading role in aging transmission via paracrine and endocrine mechanisms. EVs are successful in intercellular and interorgan communication in the aging microenvironment and age-related diseases. They have detrimental effects on downstream targets at the levels of immunity, inflammation, gene expression, and metabolism. Furthermore, EVs obtained from different donors are also promising materials and tools for antiaging treatments and are used for regeneration and rejuvenation in cell-free systems. Here, we describe the characteristics of cellular senescence and the aging microenvironment, concentrating on the production and function of EVs in age-related diseases, and provide new ideas for antiaging therapy with EVs.

SKP-SC-EVs Mitigate Denervated Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation and Improving Microcirculation

“…Maintaining the homeostasis of the regenerative microenvironment is essential for muscle growth and development. Based on the EVs delivery system, we constructed an endogenous beneficial microenvironment and activated the protection mechanism underpinning tissue regeneration, which is a promising method [ 61 , 62 ]. Increasing evidence has shown that EVs actively regulate angiogenesis in vascular endothelial cells by acting on blood vessel formation [ 63 ].…”

Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents

“…As with AT, it has been reported that the number of ASCs obtainable from SAT decreases with age [101]; probably, the same happens for ASC-derived EVs [44]. Unfortunately, results on the differences in EV characteristics obtained from young and senescent cells are still conflicting [101]. Another important issue is the weight of the donors [102], as well as the presence of metabolic pathologies [29], which reasonably alter the quality and characteristics of the EVs obtained from those cells [109].…”

“…In addition, a general limitation for all potential applications of EVs in therapy is the age of the tissue/cell donors. As with AT, it has been reported that the number of ASCs obtainable from SAT decreases with age [101]; probably, the same happens for ASC-derived EVs [44]. Unfortunately, results on the differences in EV characteristics obtained from young and senescent cells are still conflicting [101].…”

“…EV use for diagnostic purposes [92,93] Methods of EV isolation are not yet fully standardized [98] Good handling [98] EVs' storage stability is not well known [98] Small size precluding pulmonary embolism if administered in a large number and favoring crossing of the BBB [99,100] The age of tissue/cell donors influences the number of ASCs, and thereby EVs, obtainable from SAT, even though the results are still conflicting [44,75,101] Low/null expression of membrane histocompatibility markers, reducing the risk of host immune responses [99] Weight of donors and the presence of metabolic pathologies can alter EVs' quality/characteristics [29,101,102] EVs carry only a fraction of the molecules produced by the cells of origin, favoring selection for specific therapeutic purposes [100] Restriction in the range of products donated by EVs compared with entire MSCs, so that the therapeutic dose and efficacy of EVs must still be clearly defined [92] Homing certain tissues depends on their source tissue, which would be mainly useful in the case of the use of EV for targeted drug delivery [33] It is not clear how extensive the EV homing ability is. [33] EVs, similar to iPSCs and unlike MSCs, should not be tumorigenic and, in selected cases, could also serve as a new anticancer tool [103][104][105] Data are still conflicting.…”

Recent Progress of Exosome Isolation and Peptide Recognition-Guided Strategies for Exosome Research

“…Exosomes were once considered to be the waste products of cells in the original research. Nowadays, more and more studies have shown that exosomes play important roles in organisms, such as cell-to-cell communication ( Ruhland et al, 2020 ; Schneider et al, 2021 ), immune response ( Kalluri and LeBleu, 2020 ; Su et al, 2020 ), cell growth and differentiation ( Yin et al, 2021 ; Zarnowski et al, 2021 ), as well as molecular transport ( Zhu Q. et al, 2021 ). Crucially, the concentration and phenotype of exosomes have been proved to reflect the state of their parental cells and associate with the occurrence and development of various diseases, such as cancers ( Jiang et al, 2021 ), infectious diseases ( Ning et al, 2021 ; Xie et al, 2021 ), metabolic, and cardiovascular diseases ( Kalluri and LeBleu, 2020 ).…”