Age-related decline in metabolite heavy isotope content in rodent organs

Heavy isotopes are discriminated by biological systems due to kinetic isotopic effects at the biochemical/metabolic levels. How these heavy isotopes are enriched or depleted over a long term is unclear, but artificial manipulation of heavy isotope content in various organisms has produced significant impacts on biological functions, suggesting the origin may arise with intrinsic mechanisms for a functional outcome. Our previous study has revealed an age-associated decline in metabolite heavy isotope content (HIC) in the budding yeast, which could be reversed in part by supplementing heavy water, and consequently, also increased yeast lifespans. In the current study, we report a similar age-dependent decline in HIC from three types of mouse tissues: brain, heart, and skeletal muscles. Furthermore, individual tissues exhibited different patterns of HIC change over age, which appeared to match their development and maturation timelines. These results have demonstrated that age-dependent decline in HIC also exists in mammals, which is likely a traceable feature of development and perhaps aging. Thus, we believe that reversing the decline in HIC could have the potential to extend the healthspan of humans.