Regulatory Roles of Exosomes in Aging and Aging-Related Diseases

Overview

Journal Biogerontology

Specialty Geriatrics

Date 2025 Feb 18

PMID 39966192

Authors

Nanyin Xiao

Qiao Li

Guangyu Liang

Zonghao Qian

Yan Lin

Heng Zhang

Yangguang Fu

Xiao Yang

Cun-Tai Zhang

Jiankun Yang

Anding Liu

Affiliations

Soon will be listed here.

Abstract

Exosomes are small vesicles with diameters ranging from 30 to 150 nm. They originate from cellular endocytic systems. These vesicles contain a rich payload of biomolecules, including proteins, nucleic acids, lipids, and metabolic products. Exosomes mediate intercellular communication and are key regulators of a diverse array of biological processes, such as oxidative stress and chronic inflammation. Furthermore, exosomes have been implicated in the pathogenesis of infectious diseases, autoimmune disorders, and cancer. Aging is closely associated with the onset and progression of numerous diseases and is significantly influenced by exosomes. Recent studies have consistently highlighted the important functions of exosomes in the regulation of cellular senescence. Additionally, research has explored their potential to delay aging, such as the alleviatory effects of stem cell-derived exosomes on the aging process, which offers broad potential for the development and application of exosomes as anti-aging therapeutic strategies. This review aims to comprehensively investigate the multifaceted impact of exosomes while concurrently evaluating their potential applications and underscoring their strategic significance in advancing anti-aging strategies.

References

Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood M . Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011; 29(4):341-5. DOI: 10.1038/nbt.1807. View

Amariglio N, Hirshberg A, Scheithauer B, Cohen Y, Loewenthal R, Trakhtenbrot L . Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med. 2009; 6(2):e1000029. PMC: 2642879. DOI: 10.1371/journal.pmed.1000029. View

Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J, Haydar T . Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci. 2015; 18(11):1584-93. PMC: 4694577. DOI: 10.1038/nn.4132. View

Attwooll C, Denchi E, Helin K . The E2F family: specific functions and overlapping interests. EMBO J. 2004; 23(24):4709-16. PMC: 535093. DOI: 10.1038/sj.emboj.7600481. View

Babst M, Katzmann D, Meerloo T, Emr S . Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell. 2002; 3(2):271-82. DOI: 10.1016/s1534-5807(02)00220-4. View

Bai L, Wang Y . Mesenchymal stem cells-derived exosomes alleviate senescence of retinal pigment epithelial cells by activating PI3K/AKT-Nrf2 signaling pathway in early diabetic retinopathy. Exp Cell Res. 2024; 441(2):114170. DOI: 10.1016/j.yexcr.2024.114170. View

Baker D, Childs B, Durik M, Wijers M, Sieben C, Zhong J . Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature. 2016; 530(7589):184-9. PMC: 4845101. DOI: 10.1038/nature16932. View

Bartel D . Metazoan MicroRNAs. Cell. 2018; 173(1):20-51. PMC: 6091663. DOI: 10.1016/j.cell.2018.03.006. View

Bei Y, Das S, Rodosthenous R, Holvoet P, Vanhaverbeke M, Monteiro M . Extracellular Vesicles in Cardiovascular Theranostics. Theranostics. 2017; 7(17):4168-4182. PMC: 5695004. DOI: 10.7150/thno.21274. View

10.

Ben-Porath I, Weinberg R . The signals and pathways activating cellular senescence. Int J Biochem Cell Biol. 2005; 37(5):961-76. DOI: 10.1016/j.biocel.2004.10.013. View

11.

Bentires-Alj M, Barbu V, Fillet M, Chariot A, Relic B, Jacobs N . NF-kappaB transcription factor induces drug resistance through MDR1 expression in cancer cells. Oncogene. 2003; 22(1):90-7. DOI: 10.1038/sj.onc.1206056. View

12.

Borgdorff V, LLeonart M, Bishop C, Fessart D, Bergin A, Overhoff M . Multiple microRNAs rescue from Ras-induced senescence by inhibiting p21(Waf1/Cip1). Oncogene. 2010; 29(15):2262-71. DOI: 10.1038/onc.2009.497. View

13.

Borghesan M, Fafian-Labora J, Eleftheriadou O, Carpintero-Fernandez P, Paez-Ribes M, Vizcay-Barrena G . Small Extracellular Vesicles Are Key Regulators of Non-cell Autonomous Intercellular Communication in Senescence via the Interferon Protein IFITM3. Cell Rep. 2019; 27(13):3956-3971.e6. PMC: 6613042. DOI: 10.1016/j.celrep.2019.05.095. View

14.

Brookes S, Rowe J, Ruas M, Llanos S, Clark P, Lomax M . INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescence. EMBO J. 2002; 21(12):2936-45. PMC: 126048. DOI: 10.1093/emboj/cdf289. View

15.

Brookes S, Rowe J, Gutierrez Del Arroyo A, Bond J, Peters G . Contribution of p16(INK4a) to replicative senescence of human fibroblasts. Exp Cell Res. 2004; 298(2):549-59. DOI: 10.1016/j.yexcr.2004.04.035. View

16.

Campisi J . Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005; 120(4):513-22. DOI: 10.1016/j.cell.2005.02.003. View

17.

Campisi J, dAdda di Fagagna F . Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007; 8(9):729-40. DOI: 10.1038/nrm2233. View

18.

Cao H, Chen M, Cui X, Liu Y, Liu Y, Deng S . Cell-Free Osteoarthritis Treatment with Sustained-Release of Chondrocyte-Targeting Exosomes from Umbilical Cord-Derived Mesenchymal Stem Cells to Rejuvenate Aging Chondrocytes. ACS Nano. 2023; 17(14):13358-13376. DOI: 10.1021/acsnano.3c01612. View

19.

Chen C, Liu L, Ma F, Wong C, Guo X, Chacko J . Elucidation of Exosome Migration across the Blood-Brain Barrier Model In Vitro. Cell Mol Bioeng. 2017; 9(4):509-529. PMC: 5382965. DOI: 10.1007/s12195-016-0458-3. View

20.

Chen Y, Sheu J, Sun C, Huang T, Lin Y, Yip H . MicroRNA-214 modulates the senescence of vascular smooth muscle cells in carotid artery stenosis. Mol Med. 2020; 26(1):46. PMC: 7227274. DOI: 10.1186/s10020-020-00167-1. View