| Popis: |
In this paper, A Single Origin of Life and Death on Earth Hypothesis (SOLDE) is introduced that links salicylic acid (SA) to both the origin of life and aging. SOLDE predicts the existence of an as-yet-undefined, universally conserved, novel molecular target to prevent age-related decline, prevent and control noncommunicable diseases (NCDs), and extend healthspan. In plants, SA decreases the survival and replication of microbial communities under anaerobic, but not aerobic, conditions. SA also inhibits the motility of gram-negative Escherichia coli. The mechanisms by which SA exerts these effects are unclear. Since antifolates decrease the survival and replication of microbial communities, and inhibit the motility of gram-negative Burkholderia pseudomallei, it was postulated that SA might exert its effects on microbial communities by inhibiting microbial biosynthesis of tetrahydrofolate (THF) under anaerobic conditions. To start to explore this possibility, the motility of E. coli was examined under anaerobic and aerobic conditions after incubation with SA and/or methionine. Methionine, a product of THF metabolism, is an element of S-adenosylmethionine (SAM), required for E. coli motility. Low power light microscopy revealed that SA decreases E. coli motility under anaerobic, but not aerobic, conditions, and that supplemental methionine prevents this decrease. These simple findings support the proposition that SA might exert its effects on microbial communities across all three domains of life by inhibiting biosynthesis of THF under anaerobic conditions. An as-yet-undefined, universally conserved anaerobic catalyst might be the target of SA in plants. Life on Earth began 4.5 to 3.9 billion years ago under anaerobic conditions, but the origin of life is unknown. Aging, which occurs under aerobic conditions, is widely believed to result from the Hallmarks of Aging, but the underlying cause of these Hallmarks remains unclear. Now, SOLDE proposes that wildtype (wt) 12S ribosomal RNA 924-948 (Helix 45), which contains a universally conserved, double dimethylated GGAA tetraloop, is both the as-yet-undefined, universally conserved anaerobic catalyst target of SA in plants and the single origin of life on Earth. Mutant (mt) 12S rRNA 924-948, through dysregulation of universal regulators and inhibition of protein synthesis/folding under aerobic conditions, is proposed to be the single underlying cause of the Hallmarks of Aging. One billion people are expected to die from age-related NCDs over the next 25 years. Targeting mt 12S rRNA 924-948 with pharmacological and/or nutritional treatments might be the best strategy to prevent age-related decline, prevent and control NCDs, and extend healthspan. |
