Mitochondrial DNA insertions into nuclear DNA affecting chromosome segregation: Insights for a novel mechanism of immunosenescence in mice

HIV Infection, Chromosome Instability, and Micronucleus Formation

“…Cell senescence is, at least partially, a result of chromosomal damage accumulation and defective cell-cycle functioning. Genome instability, expressed by nuclear anomalies and chromosomal aberrations, can lead to defective cell division, apoptosis, cell-cycle arrest, and carcinogenesis [ 91 , 92 , 93 ]. Furthermore, MN frequency increases with aging and is associated with less proliferative lymphocytes [ 94 ].…”

“…Furthermore, MN frequency increases with aging and is associated with less proliferative lymphocytes [ 94 ]. Additionally, increased genomic instability and MN formation have an impact on lymphocyte function and immunosenescence [ 93 ]. Chromosome instability and immunosenescence are therefore connected processes that can form a vicious circle, which can be aggravated by HIV infection.…”

“…Immunoscenence is also associated with insertions of mitochondrial sequences into the nuclear DNA of T lymphocytes, which increased progressively with aging [ 93 ]. ROS generation in the mitochondria (mitROS) could damage/fragment mtDNA, with such fragments accumulating into the nuclear genome.…”

“…These processes may affect the balance of cell division, differentiation, senescence, and death, which is essential for the maintenance of tissue homeostasis. These processes could be a major contributing factor to aging and even cancer formation [ 93 , 95 , 96 ]. A robust body of evidence supports the occurrence of increased mtDNA damage and mitochondrial dysfunction in different cell types of HIV-infected individuals, including neuronal cells [ 97 , 98 , 99 , 100 , 101 , 102 , 103 ].…”