DNA/RNA Chemistry for Healthspan

Genomic integrity is continuously challenged by reactive species. Fortunately, our efficient DNA repair systems rarely miss damage, restoring more than 20,000 DNA damage per cell per day. However, DNA repair activity attenuates as we age, leading to the accumulation of DNA damage/mutations. Tragically, susceptible individuals with attenuated DNA repair activity are reported to develop cancers at a frequency of 45–85% by the age of 70. Our team is highly passionate about studying genomic integrity and its maintenance. We, as a group of biochemists, develop biochemical measures to study and modulate the systems, looking to increase the quality of life by preventing cancer, especially for elderly. FDA recommends reductions in the consumption of cooked red meats and fried foods in general. Prevailing scientific background of the recommendation has been small molecule metabolites such as PAHs and HCAs. These are generated during cooking of foods at trace levels, and alkylate biopolymers upon consumption via bio-activation. However, National Cancer Institute (NCI) states that ‘This is NOT YET DEFINITIVE’ as the carcinogenicity of these molecules has been only observed at much higher concentration compared to that in our normal diet. We suggest that DNA in food may be an actual threat. We found that the DNA in food gets significantly damaged during cooking, of which amount is 3–4 magnitudes higher than the metabolites (damaged DNA was observed at milligram range per kilogram of meat). Upon the consumption of damaged DNA, it is digested into damaged nucleosides in stomach and guts, then absorbed and salvaged. The resulting damaged nucleotides are participated in DNA synthesis, inducing DNA repair response and mutations. Messenger RNA (mRNA) therapeutics hold a great potential f