In this Opinion, I propose an epigenetic clock model that outlines how molecular modifications, such as DNA methylation, are integral components for timing endogenous biological rhythms.
Genetic and molecular modifications such as transformation, deregulation of apoptosis, proliferation, invasion angiogenesis, and metastasis are characteristics of cancer [ 4].
We recently developed the novel TRAIL-based drug platform TR3, a genetically fused trimer with the capacity for further molecular modifications such as the addition of tumor-directed targeting moieties.
Nanoparticles, with size 10 100 nm, offer a very suitable medium to carry out molecular level modifications such as the site-specific imaging and targeting in cancer cells [29].
These epigenetic marks or modifications correspond to molecular modifications of the DNA, such as methylation of cytosines and modification of proteins associated with DNA such as histone methylation, acetylation and deacetylation, and phosphorylation, without affecting the DNA sequence per se.
These observations are matched at the molecular level by epigenetic modifications such as methylation of cytosines in the DNA and methylation, acetylation, and other modifications of histone proteins wrapped around the DNA in chromosomes.
Specifically, at the molecular level, posttranslational protein modifications such as glycation, phosphorylation, deamidation, and oxidation [ 1- 3] can alter protein conformation, which may ultimately result in cross-linking and aggregation[ 4] in the cytoplasm.
It should be noted that we have not considered the possibility of molecular weight-altering post-translational modifications such as glycosylation due to the lack of comprehensive protein modification data.
It has been shown that molecular interactions between site-specific chemical modifications such as acetylation and methylation on DNA-packing histones and conserved structural modules present in transcriptional proteins are closely associated with chromatin structural changes and gene activation.
From an article review, molecular modifications strongly associate with oral carcinoma, such as p53 or RAS mutations [ 15].
In this review, we highlight molecular mechanisms linking NO-dependent post-translational modifications, such as cysteine S-nitrosylation and tyrosine nitration, to abnormal mitochondrial metabolism.
