Mitochondrial Dysfunction in Aging, HIV, and Long COVID: Mechanisms and Therapeutic Opportunities

Abstract

We hypothesize that a unified mitochondrial perspective on aging, HIV, and long COVIDreveals shared pathogenic mechanisms and specific therapeutic vulnerabilities that areoverlooked when these conditions are treated independently. Mitochondrial dysfunction isincreasingly recognized as a common factor driving aging, HIV, and long COVID. Sharedmechanisms—including oxidative stress, impaired mitophagy and dynamics, mtDNAdamage, and metabolic reprogramming—contribute to ongoing energy failure and chronicinflammation. Recent advancements highlight new therapeutic strategies such as mitochondrialtransfer, transplantation, and genome-level correction of mtDNA variants, withearly preclinical and clinical studies providing proof-of-concept. This review summarizescurrent evidence on mitochondrial changes across aging and post-viral syndromes, examinesemerging organelle-based therapies, and discusses key challenges related to safety,durability, and translation.