Emerging roles of interferon-stimulated gene-15 in age-related telomere attrition, the DNA damage response, and cardiovascular disease

María González-Amor; Beatriz Dorado; Vicente Andrés

doi:10.3389/fcell.2023.1128594

Emerging roles of interferon-stimulated gene-15 in age-related telomere attrition, the DNA damage response, and cardiovascular disease

Front Cell Dev Biol. 2023 Mar 21:11:1128594. doi: 10.3389/fcell.2023.1128594. eCollection 2023.

Authors

María González-Amor^{1

2}, Beatriz Dorado^{1

2}, Vicente Andrés^{1

2}

Affiliations

¹ CIBER Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
² Molecular and Genetic Cardiovascular Pathophysiology Laboratory, Novel Mechanisms of Atherosclerosis Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.

Abstract

Population aging and age-related cardiovascular disease (CVD) are becoming increasingly prevalent worldwide, generating a huge medical and socioeconomic burden. The complex regulation of aging and CVD and the interaction between these processes are crucially dependent on cellular stress responses. Interferon-stimulated gene-15 (ISG15) encodes a ubiquitin-like protein expressed in many vertebrate cell types that can be found both free and conjugated to lysine residues of target proteins via a post-translational process termed ISGylation. Deconjugation of ISG15 (deISGylation) is catalyzed by the ubiquitin-specific peptidase 18 (USP18). The ISG15 pathway has mostly been studied in the context of viral and bacterial infections and in cancer. This minireview summarizes current knowledge on the role of ISG15 in age-related telomere shortening, genomic instability, and DNA damage accumulation, as well as in hypertension, diabetes, and obesity, major CVD risk factors prevalent in the elderly population.

Keywords: DNA damage response; ISG15; aging; diabetes; hypertension; obesity; telomere shortening.

Publication types

Review

Grants and funding

VA lab is supported by Ministerio de Ciencia e Innovación (MICINN)/Agencia Estatal de Investigación (AEI) (grant PID2019-108489RB-I00/AEI/10.13039/501100011033) with cofund from Fondo Social Europeo “El FSE invierte en tu futuro”, the Progeria Research Foundation (grant PRF2019–77), Asociación Progeria Alexandra Peraut, Fundació Marató TV3 (grant 202033-31), and Sociedad Española de Cardiología (SEC/FEC-INV-BAS 22/005). MG-A is supported by the MCINN (post-doctoral contract FJC2021-047576-I). The CNIC is supported by the MICINN, the Instituto de Salud Carlos III, the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).