Mitochondrial function declines with age, leading to a variety of age-related diseases (metabolic, central nervous system-related, cancer, etc.) and medication usage increases with age due to the increase in diseases. Drug-induced mitochondrial toxicity has been described for many different drug classes and can lead to liver, muscle, kidney and central nervous system injury and, in rare cases, to death. Many of the most prescribed medications in the geriatric population carry mitochondrial liabilities. We have demonstrated that, over the past decade, each class of drugs that demonstrated mitochondrial toxicity contained drugs with both more and less adverse effects on mitochondria. As patient treatment is often essential, we suggest using medication(s) with the best safety profile and the avoidance of concurrent usage of multiple medications that carry mitochondrial liabilities. In addition, we also recommend lifestyle changes to further improve one’s mitochondrial function, such as weight loss, exercise and nutrition.

No abstract

Genetic modification of Gram-negative bacteria to express a desired protein within the cell's periplasmic space, located between the inner cytoplasmic membrane and the outer cell wall, can offer an attractive strategy for commercial production of therapeutic proteins and industrial enzymes. In certain applications, the product expression rate is high, and the ability to isolate the product from the cell mass is greatly enhanced because of the product's compartmentalized location within the cell. Protein release methods that increase the permeability of the outer cell wall for primary recovery, but avoid rupturing the inner cell membrane, reduce contamination of the recovered product with other host cell components and simplify final purification. This article reports representative data for a new release method employing glycol ether solvents. The example involves the use of 2-butoxyethanol (commonly called ethylene glycol n-butyl ether or EB) for selective release of a proprietary biopharmaceutical protein produced in the periplasmic space of Pseudomonas fluorescens. In this example, glycol ether treatment yielded approximately 65% primary recovery with approximately 80% purity on a protein-only basis. Compared with other methods including heat treatment, osmotic shock, and the use of surfactants, the glycol ether treatment yielded significantly reduced concentrations of other host cell proteins, lipopolysaccharide endotoxin, and DNA in the recovered protein solution. The use of glycol ethers also allowed exploitation of temperature-change-induced phase splitting behavior to concentrate the desired product. Heating the aqueous EB extract solution to 55 degrees C formed two liquid phases: a glycol ether-rich phase and an aqueous product phase containing the great majority of the product protein. This phase-splitting step yielded an approximate 10-fold reduction in the volume of the initial product solution and a corresponding increase in the product's concentration.