Genome stabilizing nanomaterials
The human genome is constantly exposed to different kinds of mutagens (externally imposed chemical, physical and biological determinants), and endogenous factors, especially genome replication errors, produced reactive oxygen species and spontaneous hydrolytic reactions (Zid et al.). Also, somatic mutations, such as aging-related mitochondrial DNA (mtDNA) mutation, could alter the stability and integrity of genomic DNA (C. B. Park & Larsson, 2011). The accumulation of mutations and damages with time may lead to genetic instability and could impact transcriptional pathways and gene functionality. These processes could alter cells function and induce a disturbance in tissue and organismal homeostasis, leading to age-associated disorders, such as carcinogenesis, neurodegenerative diseases, and some premature aging disorders such as Werner syndrome and Bloom syndrome (Burtner & Kennedy, 2010; Moskalev et al., 2013). On the other hand, various forms of epigenetic changes and microsatellite instability, including\sout, modification of histone, methylation of DNA, and mutation of microRNA and telomere shortening, have a reverse effect on the stability of the human genome. Several diseases caused by aging like cancer, atherosclerosis, diabetes, neurodegenerative complications, and immune response deficiency are associated with epigenetic disorders (Calvanese, Lara, Kahn, & Fraga, 2009). Furthermore, telomere dysfunction and consequent genomic instability have a critical influence on aging at a cellular level involved in the induction of senescence or apoptosis that might contribute to age-related diseases (Innan, Veitia, & Govindaraju, 2020). Having knowledge of signaling mechanisms associated with DNA stability and mtDNA integrity may help us to delay aging and potentially reduce the incidence of many genomic related disorders (Blackburn, Greider, & Szostak, 2006).
The metal nanoparticles can induce genotoxicity and mutagenicity by exposure to the genome or damaging the mitotic separation and its structural components (Kumar & Dhawan, 2013), in contrary, some nanoparticles can be used in delivering the nucleic materials (i.e., DNA, RNA, and siRNA) and oligonucleotides (including genes). The modification of genetic materials has been reported in various chronic disorders (Rea et al., 2018). Gene therapy using nanomedicine need preliminary detection of the genetic disorders in targeted cells. The composite nanoparticle can alter the pattern of transcription and translation of genes leading to modulation of gene functions through genetic manipulation in targeted tissue (Shajari, Mansoori, Davudian, Mohammadi, & Baradaran, 2017).
According to illumined molecular mechanisms of age-related complications, nanomedicine may be a potent future tool in the development of appropriate medications for age-associated genetic malfunctions via gene manipulation approaches.