Aging is characterized by a significant increase of the probability of death. In addition, it is typically characterized by a sharp increase in a probability of occurrence of various pathologies and conditions that are not immediately life threatening, but are associated with the aging process. Such pathologies and conditions (symptoms of aging) in mammals include, but are not limited to for example, increased incidence of cancer, loss of sight (cataract), and other sensory deterioration, skin and hair conditions (e.g., alopecia), arthritis, and an age-associated decrease in weight due to the death of muscular and fatty cells, muscle weakness and other mobility deterioration, and the like.
Considerable interest has been devoted to identifying new medications and agents that inhibit aging (e.g., mitigate or slow the onset of one or more symptoms of aging) or improve healthspan.
Vitamins A, C, and E have been observed to increase the duration of life in Drosophila (see, e.g., Baker (1993) Toxicol Ind. Health., 9: 163-186). However, hypersaturation of the organism with these vitamins may result in a quick development of hypervitominosis, and may have a negative effect on the functional state of body systems and organs.
There are also known agents, that express geroprotective and antioxidant activity, based on the compound ethoxyquin (santoquin). This compound increased the duration of life of C3H mice, when it was added to the food (see, e.g., Comfort et al. (1971) Nature., 229: 254-255). Longevity of life of the laboratory animals was also increased as a result of the administration of a low toxic water soluble antioxidant 2-ethyl-6-methyl-3-hydroxypyridine chlorohydrate, which is a structural analog of the vitamin B6 (see, e.g., Obukhova (1975) Uspekhi Khimii (Russ.), 44: 1914-1925). Insignificant prolongation of life was observed in experiments with 2-mercaptoethanol amine, cysteine, centrophenoxine, butylhydroxyl toluene, glutathione, 3-hydroxypyridine, lactic acid, and gluconic acid (see, e.g., Obukhova and Emmanuel (1988) Obschie Problemy Biologii (Russ.)/VINITI, 4: 44-80).
A therapeutic agent, gerovital, that contains procaine has been used as a geroprotective medication (e.g., Mashkovsky (1993) Medicinal drugs (Russ.).—Moscow, Medicina, part 1—chapter 3—p. 375). However, there were incidents of its negative effect on the cardio-vascular functions, disturbances in sleep, anxiety, and muscle aches and joints aches.
Compounds with alleged geroprotective properties, include the endogenous compounds melatonin and N-acetylserotonin (NAS). These compounds have antioxidant properties and, according to one of theories on the mechanism of ageing, should have geroprotective effect (see, e.g., Heng-Long Hu et al. (2000) Mechanisms of Ageing and Development 121: 217-230). Experiments with C57B1 mice demonstrated that melatonin and its precursor NAS were capable of prolonging the life of the male mice, when they received these compounds from the age of 2 months. However, these compounds were ineffective in experiments with male mice of the same line, when animals received these compounds from the age of 12 months (see, e.g., Oxenkrug et al. (2001) Ann. N.Y. Acad. Sci. 939: 190-199).
USPTO Backgrounds
USPTO Backgrounds