Mitochondrial Dysfunction and Aging: Insights from the Analysis of Extracellular Vesicles.

Author: Picca A1,2, Guerra F3, Calvani R4,5, Bucci C6, Lo Monaco MR7, Bentivoglio AR8,9, Coelho-Júnior HJ10,11, Landi F12,13, Bernabei R14,15, Marzetti E16
Author Information:
1Università Cattolica del Sacro Cuore, Institute of Internal Medicine and Geriatrics, 00168 Rome, Italy. anna.picca1@gmail.com.
2Fondazione Policlinico Universitario "Agostino Gemelli" IRCSS, 00168 Rome, Italy. anna.picca1@gmail.com.
3Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy. guerraflora@gmail.com.
4Università Cattolica del Sacro Cuore, Institute of Internal Medicine and Geriatrics, 00168 Rome, Italy. riccardo.calvani@gmail.com.
5Fondazione Policlinico Universitario "Agostino Gemelli" IRCSS, 00168 Rome, Italy. riccardo.calvani@gmail.com.
6Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy. cecilia.bucci@unisalento.it.
7Fondazione Policlinico Universitario "Agostino Gemelli" IRCSS, 00168 Rome, Italy. mariarita.lomonaco@policlinicogemelli.it.
8Fondazione Policlinico Universitario "Agostino Gemelli" IRCSS, 00168 Rome, Italy. annarita.bentivoglio@unicatt.it.
9Università Cattolica del Sacro Cuore, Institute of Neurology, 00168 Rome, Italy. annarita.bentivoglio@unicatt.it.
10Università Cattolica del Sacro Cuore, Institute of Internal Medicine and Geriatrics, 00168 Rome, Italy. coelhojunior@hotmail.com.br.
11Applied Kinesiology Laboratory⁻LCA, School of Physical Education, University of Campinas, 13.083-851 Campinas-SP, Brazil. coelhojunior@hotmail.com.br.
12Università Cattolica del Sacro Cuore, Institute of Internal Medicine and Geriatrics, 00168 Rome, Italy. francesco.landi@unicatt.it.
13Fondazione Policlinico Universitario "Agostino Gemelli" IRCSS, 00168 Rome, Italy. francesco.landi@unicatt.it.
14Università Cattolica del Sacro Cuore, Institute of Internal Medicine and Geriatrics, 00168 Rome, Italy. roberto.bernabei@unicatt.it.
15Fondazione Policlinico Universitario "Agostino Gemelli" IRCSS, 00168 Rome, Italy. roberto.bernabei@unicatt.it.
16Fondazione Policlinico Universitario "Agostino Gemelli" IRCSS, 00168 Rome, Italy. emanuele.marzetti@policlinicogemelli.it.
Conference/Journal: Int J Mol Sci.
Date published: 2019 Feb 13
Other: Volume ID: 20 , Issue ID: 4 , Special Notes: doi: 10.3390/ijms20040805. , Word Count: 212


The progressive decline of cell function and integrity, manifesting clinically as increased vulnerability to adverse outcomes and death, is core to biological aging. Mitochondrial dysfunction, oxidative stress, altered intercellular communication (including chronic low-grade inflammation), genomic instability, telomere attrition, loss of proteostasis, altered nutrient sensing, epigenetic alterations, and stem cell exhaustion have been proposed as hallmarks of aging. These "aging pillars" are not mutually exclusive, making the matter intricate and leaving numerous unanswered questions. The characterization of circulating extracellular vesicles (EVs) has recently allowed specific secretory phenotypes associated with aging to be identified. As such, EVs may serve as novel biomarkers for capturing the complexity of aging. Besides the mitochondrial⁻lysosomal axis, EV trafficking has been proposed as an additional layer in mitochondrial quality control. Indeed, disruption of the mitochondrial⁻lysosomal axis coupled with abnormal EV secretion may play a role in the pathogenesis of aging and several disease conditions. Here, we discuss (1) the mechanisms of EV generation; (2) the relationship between the mitochondrial⁻lysosomal axis and EV trafficking in the setting of mitochondrial quality control; and (3) the prospect of using EVs as aging biomarkers and as delivery systems for therapeutics against age-related conditions.

KEYWORDS: biomarkers; exosomes; mitochondrial biogenesis; mitochondrial dynamics; mitochondrial quality control; mitochondrial-derived vesicles (MDVs); mitochondrial–lysosomal axis; mitophagy

PMID: 30781825 DOI: 10.3390/ijms20040805

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