title: Synthetic mitochondria as therapeutics against systemic aging: a hypothesis.
abstract: We hypothesize herein that synthetic mitochondria, engineered, or reprogrammed to be more energetically efficient and to have mildly elevated levels of reactive oxygen species (ROS) production, would be an effective form of therapeutics against systemic aging. The free radical and mitochondria theories of aging hold that mitochondria-generated ROS underlies chronic organelle, cell and tissues damages that contribute to systemic aging. More recent findings, however, collectively suggest that while acute and massive ROS generation during events such as tissue injury is indeed detrimental, subacute stresses, and chronic elevation in ROS production may instead induce a state of mitochondrial hormesis (or "mitohormesis") that could extend lifespan. Mitohormesis appears to be a convergent mechanism for several known anti-aging signaling pathways. Importantly, mitohormetic signaling could also occur in a non-cell autonomous manner, with its induction in neurons affecting gut cells, for example. Technologies are outlined that could lead towards testing of the hypothesis, which include genetic and epigenetic engineering of the mitochondria, as well as intercellular transfer of mitochondria from transplanted helper cells to target tissues.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Medical Drive, 117597, Singapore.
authors.forename: Bor Luen
authors.initials: BL
authors.lastname: Tang
mesh_terms: D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D050259:Genes, Mitochondrial; D035683:MicroRNAs / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D045222:Electron Transport Chain Complex Proteins; D035683:MicroRNAs; D017382:Reactive Oxygen Species
keywords: aging; mitochondria; synthetic biology