Roles of Extracellular Vesicles in the Aging Microenvironment and Age-related Diseases

Overview

Journal J Extracell Vesicles

Publisher Wiley

Date 2021 Oct 5

PMID 34609061

Citations 69

Authors

Yujia Yin

Huihui Chen

Yizhi Wang

Ludi Zhang

Xipeng Wang

Affiliations

Soon will be listed here.

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.

Citing Articles

The Role of Extracellular Vesicles in Aging and Age-Related Disorders.

Ganesh B, Padinjarathil H, Rajendran R, Ramani P, Gangadaran P, Ahn B Antioxidants (Basel). 2025; 14(2).

PMID: 40002364 PMC: 11851802. DOI: 10.3390/antiox14020177.

Extracellular vesicles: their challenges and benefits as potential biomarkers for musculoskeletal disorders.

Sung S, Seo M, Park W, Lim Y, Park S, Lee G J Int Med Res. 2025; 53(2):3000605251317476.

PMID: 39973226 PMC: 11840854. DOI: 10.1177/03000605251317476.

Delivering miR-23b-3p by small extracellular vesicles to promote cell senescence and aberrant lipid metabolism.

Jin Y, Sun G, Chen B, Feng S, Tang M, Wang H BMC Biol. 2025; 23(1):41.

PMID: 39934790 PMC: 11817603. DOI: 10.1186/s12915-025-02143-9.

MSC-sEVs exacerbate senescence by transferring bisecting GlcNAcylated GPNMB.

Ma Y, Zhao C, Feng J, Gou J, Kang E, Guan F Stem Cell Res Ther. 2025; 16(1):23.

PMID: 39849576 PMC: 11756183. DOI: 10.1186/s13287-025-04140-9.

Therapeutic Efficacy and Promise of Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles in Aging and Age-Related Disorders.

Zhang A, Li Q, Chen Z Int J Mol Sci. 2025; 26(1.

PMID: 39796081 PMC: 11719504. DOI: 10.3390/ijms26010225.

References

Soukas A, Hao H, Wu L . Metformin as Anti-Aging Therapy: Is It for Everyone?. Trends Endocrinol Metab. 2019; 30(10):745-755. PMC: 6779524. DOI: 10.1016/j.tem.2019.07.015. View

Miao Y, Cui Z, Gao Q, Rui R, Xiong B . Nicotinamide Mononucleotide Supplementation Reverses the Declining Quality of Maternally Aged Oocytes. Cell Rep. 2020; 32(5):107987. DOI: 10.1016/j.celrep.2020.107987. View

Cusanelli E, Perez Romero C, Chartrand P . Telomeric noncoding RNA TERRA is induced by telomere shortening to nucleate telomerase molecules at short telomeres. Mol Cell. 2013; 51(6):780-91. DOI: 10.1016/j.molcel.2013.08.029. View

Buratta S, Urbanelli L, Sagini K, Giovagnoli S, Caponi S, Fioretto D . Extracellular vesicles released by fibroblasts undergoing H-Ras induced senescence show changes in lipid profile. PLoS One. 2017; 12(11):e0188840. PMC: 5705128. DOI: 10.1371/journal.pone.0188840. View

Georgilis A, Klotz S, Hanley C, Herranz N, Weirich B, Morancho B . PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells. Cancer Cell. 2018; 34(1):85-102.e9. PMC: 6048363. DOI: 10.1016/j.ccell.2018.06.007. View

Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S . Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism. Aging Cell. 2017; 16(3):564-574. PMC: 5418203. DOI: 10.1111/acel.12587. View

Silveira J, Winger Q, Bouma G, Carnevale E . Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-β signalling during follicle development in the mare. Reprod Fertil Dev. 2015; 27(6):897-905. DOI: 10.1071/RD14452. View

Yu B, Ma J, Li J, Wang D, Wang Z, Wang S . Mitochondrial phosphatase PGAM5 modulates cellular senescence by regulating mitochondrial dynamics. Nat Commun. 2020; 11(1):2549. PMC: 7242393. DOI: 10.1038/s41467-020-16312-7. View

Jia L, Qiu Q, Zhang H, Chu L, Du Y, Zhang J . Concordance between the assessment of Aβ42, T-tau, and P-T181-tau in peripheral blood neuronal-derived exosomes and cerebrospinal fluid. Alzheimers Dement. 2019; 15(8):1071-1080. DOI: 10.1016/j.jalz.2019.05.002. View

10.

Raval A, Martinez C, Mejias N, de Rivero Vaccari J . Sexual dimorphism in inflammasome-containing extracellular vesicles and the regulation of innate immunity in the brain of reproductive senescent females. Neurochem Int. 2018; 127:29-37. DOI: 10.1016/j.neuint.2018.11.018. View

11.

Ozcan S, Alessio N, Acar M, Mert E, Omerli F, Peluso G . Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses. Aging (Albany NY). 2016; 8(7):1316-29. PMC: 4993333. DOI: 10.18632/aging.100971. View

12.

Oh B, Lee S, Cho H, Park Y, Kim J, Yoon S . Cystatin SN inhibits auranofin-induced cell death by autophagic induction and ROS regulation via glutathione reductase activity in colorectal cancer. Cell Death Dis. 2017; 8(3):e2682. PMC: 5386512. DOI: 10.1038/cddis.2017.100. View

13.

En A, Takauji Y, Ayusawa D, Fujii M . The role of lamin B receptor in the regulation of senescence-associated secretory phenotype (SASP). Exp Cell Res. 2020; 390(1):111927. DOI: 10.1016/j.yexcr.2020.111927. View

14.

Malaquin N, Olivier M, Martinez A, Nadeau S, Sawchyn C, Coppe J . Non-canonical ATM/MRN activities temporally define the senescence secretory program. EMBO Rep. 2020; 21(10):e50718. PMC: 7534619. DOI: 10.15252/embr.202050718. View

15.

Xu P, Xin Y, Zhang Z, Zou X, Xue K, Zhang H . Extracellular vesicles from adipose-derived stem cells ameliorate ultraviolet B-induced skin photoaging by attenuating reactive oxygen species production and inflammation. Stem Cell Res Ther. 2020; 11(1):264. PMC: 7329484. DOI: 10.1186/s13287-020-01777-6. View

16.

Nanbo A, Kawanishi E, Yoshida R, Yoshiyama H . Exosomes derived from Epstein-Barr virus-infected cells are internalized via caveola-dependent endocytosis and promote phenotypic modulation in target cells. J Virol. 2013; 87(18):10334-47. PMC: 3753980. DOI: 10.1128/JVI.01310-13. View

17.

Deng S, Zhou X, Ge Z, Song Y, Wang H, Liu X . Exosomes from adipose-derived mesenchymal stem cells ameliorate cardiac damage after myocardial infarction by activating S1P/SK1/S1PR1 signaling and promoting macrophage M2 polarization. Int J Biochem Cell Biol. 2019; 114:105564. DOI: 10.1016/j.biocel.2019.105564. View

18.

Espada L, Dakhovnik A, Chaudhari P, Martirosyan A, Miek L, Poliezhaieva T . Loss of metabolic plasticity underlies metformin toxicity in aged Caenorhabditis elegans. Nat Metab. 2020; 2(11):1316-1331. DOI: 10.1038/s42255-020-00307-1. View

19.

Chen B, Sun Y, Zhang J, Zhu Q, Yang Y, Niu X . Human embryonic stem cell-derived exosomes promote pressure ulcer healing in aged mice by rejuvenating senescent endothelial cells. Stem Cell Res Ther. 2019; 10(1):142. PMC: 6528288. DOI: 10.1186/s13287-019-1253-6. View

20.

Hargitai R, Kis D, Persa E, Szatmari T, Safrany G, Lumniczky K . Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander Effect. Antioxidants (Basel). 2021; 10(2). PMC: 7911176. DOI: 10.3390/antiox10020156. View