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.