X-Message-Number: 23318 Date: Sun, 25 Jan 2004 20:32:56 -0800 (PST) From: Doug Skrecky <> Subject: Prolongation of the Life Span in Rats Here's a quote from Saul Kent's article entitled Can nucleic acid therapy reverse the degenerative processes of aging? Geriatrics October 1977 130-136 " Of particular note is a study by English physician Max Odens in which weekly injections of DNA and RNA were given to five rats with a normal maximum life span of 800 to 900 days; treatment began at the age of 750 days. All the untreated rats died before the age of 900 days, while four treated rats survived to ages of 1,600 to 1,900 days, and one rat survived 2,250 days. This degree of prolongation of the life span is unparalleled in gerontological research. But few investigators have paid attention to this study - despite the remarkable conclusion - because of its small size and limited data." Although lifespan studies on rodents treated orally with nucleotides have been completed, with largely negative results, no follow-up experiment using injectable DNA & RNA has ever been done. Back in 1997 I made an attempt at this, when I spent $253.45 to purchase a 2 year old Fisher 344 rat from Harlan Sprague Dawley, Inc. A local graduate gerontology student, from the university of British Columbia obtained some injectable salmon testes DNA & some torula yeast RNA from Sigma (for $91.70), and tried to repeat this experiment. Unfortunately, due to a mistake in mixing the DNA, & RNA with solvent, the subject rat immediately died, after being injected for the first time. That was the end of the experiment! In retrospect it is unlikely that our attempt to replicate the experiment could have succeeded, since we did not know what type of DNA, or RNA was used by Max Odens. In an incredible omission, he never mentioned the source of the DNA or RNA he used in his report. He only mentioned that the RNA was "ordinary", whatever that means. However since he quoted a lifespan study in C3H/HEJ mice, which used yeast RNA, then a reasonable assumption would be that yeast RNA was used for his injections. This still leaves the source of the DNA used, as an complete unknown. Any attempt to replicate his experiment would first have to resolve this omission. Injectible (but not oral) DNA vaccines are an extremely effective means for inducing an immune response against pathogen DNA, as well as inducing autoimmune disorders, and even paradoxically inducing immune tolerance. A brief review of the Max Odens experiment appeared in Nutrition Reviews Vol 32, No. 10 October 1974 316- 317. Quote: "The Stuff on Which Quackery Thrives? Quackery in nutrition and medicine is discouraged vigorously by ethical, competent health professionals because of actual or potential health hazards, economic factors, or the possibility that adherents to such practices may bypass successful orthodox treatment. One device by which misinformation can be combatted by scientists is educating the public to demand documentation of claims. A recent issue of the Journal of the American geriatrics Society included a report by M. Odens that weekly injections of DNA and RNA more than doubled the life span of rats. Ten 750-day old rats of a strain said to ahve a usual life span of 800 to 900 days were fed the same diet (composition unspecified). Five received weekly injections of DNA and RNA (concentration, source, and purity unspecified). The five untreated rats were said to have looked old, moved slowly, failed to eat much, and lost weight after 12 weeks while the treated rats looked younger and were very lively. The untreated rats were all dead by 900 days of age. The untreated rats were all dead by 900 days of age; the injected rats died between 1600 and 2250 days of age. Doubling the life span of any mammal is dramatic, and potentially significant. Unfortunately, this paper contains insuffient information for evaluation or repetition. Absent from the report are all data concerning prior nutritional and health status, strain, sex, and weight of the experimental animals, caging conditions, criteria of assignment to treatments, full description of either the injection solution or the experimental diet, and information on the cause of death. The study of aging and longevity is difficult even under the best experimental conditions. The publication in recognized professional journals of startling claims based upon uncritically designed and described experimental results constitutes a disservice to science and the public by both the authors and the editors." Despite extreme reservations about the format of Max Odens' research report, I can find no serious reason to doubt his results. In think Odens probably did produce a 2250 day old rat. Due to copywrite, it is generally considered that one should not quote an entire research article. However I'm willing to take a chance that the Journal of the American Geriatrics Society is not going to overtly object to my quoting the entire text from the "uncritically designed and described experimental results" obtained by Max Odens . For the first time, here in its unabridged from, is the complete text from: Journal of the American Geriatrics Society Vol. XXI No.10 1973 Prolongation of the Life Span in Rats Max Odens, MD, DTM* London, England * Deputy President, International Society for Research in Diseases of Civilization & Vital Substances, 26 Weimers Hof, Luxembourg. Address: 2 Devonshire Place, London W1, England. Abstract: To test the effect of RNA-DNA in preventing the deleterious effects of old age, and experiment was conducted that involved 10 rats with a normal life span of 800-900 days. All were fed the same diet; 5 rats were not treated, and 5 were given weekly injections of DNA + RNA. After twelve weeks the difference in appearance, weight and alertness was remarkable. The 5 untreated rats died before 900 days. Of the treated rats, 4 died at ages of 1600 - 1900 days, and 1 at 2250 days. A parallel cannot be drawn with aging in human beings fed RNA-DNA, but the findings on rats may have some application to cellular studies on cancer. Several theories have been proposed concerning the role of DNA and RNA in aging (1-5). Certain qualitative changes occur in DNA with aging (6), and also changes in RNA synthesis and metabolism (7,8). The conflicting results of many investigations (9-13) challenge as well as support these theories. The link between RNA synthesis and vitamin A (14), the hormonal influence over RNA synthesis (15), further indicate the complexity of the processes active in aging. The effect of RNA supplementation on the memory and well-being of old people has been the subject of many conflicting findings. It has been reported (16,17) that supplementation of elderly patients' meals with exogenous RNA (measuring in grams) for a relatively long period (measured in months) enhances well-being and, if continued, improves memory. These conclusions are supported by the results of work with rats (18). However, the results of another study (19) in which old people were given RNA daily (measured in milligrams) for shorter periods (measured in weeks) indicate no improvement. RNA is metabolized and enters the bloodstream in physiologically significant amounts when ingested after food intake (20). It is specific in restoring nucleic protein synthesis in isolated cell nuclei (21). The foregoing observations led to a consideration of the possible role in aging of the accumulated cellular insult from repeated virus infections incurred over a lifetime, and the prevention of these deleterious effects in rats by weekly injections of exogenous DNA and RNA. MATERIALS AND METHODS Ten rats of a strain, in which the life span varies between 800 and 900 days, were selected for the experiment when they were each 750 days old. They were given the same diet. Group A, the controls, were not treated. Group B recieved weekly injections of DNA solution in water saturated with chloroform (3 mg per ml) plus ordinary RNA. All necessary determinations such as temperature and weight were made. The charts were compared every day. After twelve weeks of injections, Group B rats looked younger, were very lively, and had gained weight (1.5-2.3 gm). Group A rats looked old, moved slowly, did not eat much, and had lost weight. the difference was remarkable. All the untreated rats died before 900 days. Of the treated rats, 4 died aged between 1600 and 1900 days. One rat lived 2250 days. DISCUSSION Many of the tissues of aged persons have characteristics which seem to have stemmed from a process of cell replication that alters slowly but surely over the years. Nevertheless, the aging process at the cellular level can vary so remarkably between individuals that it is not always possible for pathologists to grade unidentified tissue specimens according to age. If a virus takes over the cells, the production of protein is changed and the cell begins to die slowly. Evidence of the original virus infection can be carried over into daughter cells through mitotic division (22). Possibly one of the characteristics of cells in aging is the accumulation of viral debris as imprints of prior viral infection, regardless of how trivial or how serious the effect of the original infection on the well-being of the host. If such be the case, it is reasonable to assume that protein synthesis by DNA and RNA for cell renewal is somehow interfered with by such viral debris. On the other hand, exogenous RNA greatly improves the life span C3H/HEJ mice challenged by a syngeneic tumor, when given after the tumor challenge and preceded by immunization. The mechanism by which yeast RNA influences this process is unknown (23). The life span of laboratory rats is normally 800-900 days, although it varies slightly in different countries. The results of the present investigation on 5 untreated and 5 treated rats show that, with weekly injections of DNA and RNA, and life span of 4 rats was doubled on the average, and the life span of the fifth rat was more than trebled. Although it is tempting to think in terms of the possibility of an equivalent prolongation of the life span of human beings accomplished by injections of DNA and RNA, it should be emphasized that the parallels between aging in rats and aging in humans are not only unknown but are entirely outside the scope of this experiment. Postmortem results must still be evaluated by the electron microscope, and will form the basis of another paper. There is one question to be answered. Can supplementary exogenous DNA and RNA strenghten cellular resistance to the invasion of viruses implicated in the etiology of cancer? Cancer researchers should consider experiments along these lines. Acknowledgment My thanks to Professor Dr. An der Lan of the Zoological Institute of the University of Innsbruck for his useful advice concerning the animal experiments. REFERENCES 1. Alexander P: The role of DNA lesions in the processes leading to aging in mice, Symp Soc Exper Biol 21: 29 1967. 2. Medvedev ZhA: Aging at the molecular level and some speculations concerning maintaining the functioning of systems for replicating specific macromolecules, in Biological Aspects of Aging, ed. by N. W. Shock. New York, Columbia Univ. Press 1962. 3. von Hahn HP: The role of desoxyribonucleic acid (DNA) in the aging process, Gerontologia 8: 168, 1968. 4. Sinex FM: Genetic mechanisms of aging, J Gerontol 21: 340 1966 5. Wulff VJ Quastler H and Sherman FG: An hypothesis concerning RNA metabolism and aging, Proc US Nat Acad Sci 48: 1373, 1962. 6. von Hahn HP: Age-dependant thermal denaturation and viscosity of crude and purified desoxyribonucleic acid prepared from bovine thymus, Gerontologia 8: 123, 1963. 7. Mainwaring WIP: Changes in the ribonucleic acid metabolism of aging mouse tissue with particular reference to prostate gland, Biochem J 110: 79, 1968. 8. Devi A, Lindsay P, Raina PS et all: Effect of age on some aspects of the synthesis of ribonucleic acid, Nature 212: 474 1966. 9. Enesco HE: A cytophotometric analysis of DNA content of rat nuclei in aging, J Gerontol 22: 445, 1967. 10. Geary S and Florini JR: effect of age on the rate of protein synthesis in isloated perfused mouse hearts, J Gerontol 27: 325 1972 11. Sobel H: Effect of age on cardiac metabolism. Proc 3rd Annual Meeting of International Study Group for Research in Cardiac Metabolism, Stowe, Vermont, June 29-July 1, 1970. 12. Britton VJ, Sherman FG and Florini JR: Effect of age on RNA synthesis by nuclei and soluable RNA polynerases from liver and muscle of C57BL/6J mice, J Gerontol 27: 188 1972. 13. Beauchene RE, Roeder LM and Barrows CH Jr: The effect of age and of ethionine feeding on the ribonucleic acid and protein synthesis of rats, J Gerontol 22: 318, 1967. 14. Kaufman DG, Baker MS, Smith JM et all: RNA metabolism in tracheal epithelium: alteration in hamsters defient in vitamin A, Science 177: 1105, 1972. 15. Zolakar M: Hormonal control of RNA synthesis as a developmental problem, J Gerontol 22 (II): 17, 1967. 16. Odens M: R.N.A. effects on memory, Vitalstoffe 14: 144, 1969. 17. Odens M: R.N.A. effects on memory (continues), Vitalstoffe 15: 172, 1970. 18. Solyon L, Enesco HE and Beaulieu MA: The effects of RNA on learning and activity in old and young rats, J Gerontol 22: 1, 1967. 19. Britton A, Bernstein LL, Brunse AJ et al: Failure of ingestion of RNA to enahnce human learning, j Gerontol 27: 478, 1972. 20. Allfrey V and Mirsky AE: Some DNA-dependent synthetic systems of isolated cell nuclei, Tr New York Acad Sci 21: 3, 1958-59. 21. Rigby PG: The effects of "exogeous" RNA on the improvement of syngeneic tumor immunity, Cancer Res, 31: 4, 1971. 22. Odens M: Can We Delay Old Age? Lecture given at the 18th Internat. Congress, Internat. Soc. for Research on Diseases of Civilization, Berlin, Berlin, Sept. 1972. 23. Rigby PG: The effect of "exogenous" RNA on the improvement of syngeneic tumor immunity, Cancer Res 31: 4, 1971. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=23318