Extracellular Vesicles in Aging: An Emerging Hallmark?

Abstract

Extracellular vesicles (EVs) are membrane-enclosed particles secreted by cells and circulating in body fluids. Initially considered as a tool to dispose of unnecessary material, they are now considered an additional method to transmit cell signals. Aging is characterized by a progressive impairment of the physiological functions of tissues and organs. The causes of aging are complex and interconnected, but there is consensus that genomic instability, telomere erosion, epigenetic alteration, and defective proteostasis are primary hallmarks of the aging process. Recent studies have provided evidence that many of these primary stresses are associated with an increased release of EVs in cell models, able to spread senescence signals in the recipient cell. Additional investigations on the role of EVs during aging also demonstrated the great potential of EVs for the modulation of age-related phenotypes and for pro-rejuvenation therapies, potentially beneficial for many diseases associated with aging. Here we reviewed the current literature on EV secretion in senescent cell models and in old vs. young individual body fluids, as well as recent studies addressing the potential of EVs from different sources as an anti-aging tool. Although this is a recent field, the robust consensus on the altered EV release in aging suggests that altered EV secretion could be considered an emerging hallmark of aging.

Keywords: aging; extracellular vesicles (EVs); senescence; senescence-associated secretory phenotype (SASP).

Figure 1

Aging hallmarks. The colored puzzle pieces represent the different hallmarks of aging: in green the original hallmarks and in blue the new hallmarks defined at the Copenhagen Meeting on Aging 2022. In this review, we propose “the alteration in extracellular vesicles” as an additional new hallmark of aging (in red). Other potential new hallmarks emerging from future studies will lead to puzzle completion. Created by BioRender.com (accessed on 18 January 2023).

Figure 2

The role of EVs in aging. Extracellular vesicles are known to influence aging and age-related diseases. Both young and senescent cells are capable of secreting EVs. Secreted EVs from young and senescent cells can induce rejuvenation or aging in senescent and young recipient cells, respectively, as indicated by arrows. The molecular mechanisms by which EVs from young cells induce rejuvenation of old cells can be divided into 3 main groups: (1) reduction of aging markers [145,147,148,149,151,161], (2) increase of anti-aging effects [131,147,150,160], and (3) anti-aging potential [151,154,155,156,159]. The arrows between the two types of cells mean that both cells are able to secrete EVs. Relevant literature is provided for each group. Mechanisms by which EVs from senescent cells may promote aging and age-related diseases in young cells include promotion of vascular calcification, cardiac fibrosis, reduction of cell differentiation, and others. References to relevant publications on these topics are also provided [125,114,115,116,141,142,143,144,162]. Created with BioRender.com accessed on 20 January 2023.