IV. Induced anti-senescent genetic variation in embryonal stem cells (ESCs)
An idea just in the planning stage is to select embryonal stem cells (ESCs) in vitro for phenotypes that may retard aging. ESCs are immortal, but develop into normal tissues, including germ cells, after injection into an early embryo. Thus, selection at this level will be rapid.
Initially, we will transfect ESC lines with genes that should improve DNA repair and resist oxidative free radicals, both in mitochondrian and somatic genes. Then we will select clones that are resistant to damage from mutagens and oxidants, and thus may have incorporated the new genes in patterns useful for generalized cellular protection. We will reject transformed clones that have abnormal growth patterns or abnormal DNA contents. We will test if clones are resistant to various mutagenic and oxidative stimuli such as paraquat, peroxide, hyperbaric oxygen, and gamma irradiation, comparing them with clones selected directly for resistance to paraquat.
We will test whether mice produced from resistant ESCs have improved DNA repair, are more resistant to oxidants, and have increased life spans.