A large body of evidence links the species of life span and oxidative stress. Not unexpectedly, mitochondria have drawn much attention as the site of that oxidative stress in the aging process. To cite a specific example, extension of murine life span with overexpression of catalase targeted to mitochondria has been shown. (1) In chronically ill patients with clinical signs of accelerated aging, the occurrence of respiratory-to-fermentative shift in ATP production -- designated dysoxygenosis -- has been documented with measurements of of increased urinary excretion of Krebs cycle metabolites. Specifically, in a series of 236 such patients, the frequency of increased urinary excretion of such acids closely followed the order of those metabolites in the Krebs cycle -- citrate excretion was seen most frequently followed by that of succinate, aconate, and fumarate. Increased excretion of 2-oxo-glutarate, and malate was not seen in any patients. (2)
For achieving oxygen homeostasis through restoration of mitochondrial membrane potential and function in conditions associated with mitochondrial dysfunction, we have experimentally and clinically evaluated a novel phospholipid fraction designated NT factor. In Fisher 344 male rats, NT factor significantly improved mitochondrial membrane potential and decreased age-related hearing loss (3). In human subjects with disabling fatigue, the use of NT factor improved mitochondria membrane potential (as measured by rhodamine transport in leukocytes) and reduced clinical symptomatology. (4) The data obtained with the last three studies will be presented, and questions raised by the findings will be discussed.
1. Schriner SE, Linford NJ, Martin GM, et al. Extension of urine life span by overexpression of catalase targeted to mitochondria. ScienceExpress. www.scienceexpress.org/5May, 2005.
2. Ali M. Respiratory-to-Fermentative (RTF) Shift in ATP Production in Chronic Energy Deficit States. Townsend Letter for Doctors and Patients. 2004. August/Sept. issue. 64-65.
3. Seidman MD, Khan MJ, Tang WX, et al. Influence of lecithin on mitochondrial DNA and age-related hearing loss. Otolaryngol Head Neck Surgery. 2002;127:138-44.
4. Agajanyan M, Vasilevko V, Ghochikyan A, et al. Journal of Chronic fatigue Syndrome. 2003;1:8-15.