X-Message-Number: 9157 Date: Thu, 12 Feb 1998 17:04:02 -0800 (PST) From: Doug Skrecky <> Subject: C57BL/6J Mice Longevity Database (updated) C57BL/6J MICE LONGEVITY DATABASE (Updated by Doug Skrecky February 11, 1998) The following database lists the effect of various treatments on average life span of C57 black jax 6 (C57BL/6J) mice. The percent change in average life span is listed under the %CHANGE columns, relative to either the CONTROL group used in an individual experiment, or relative to the Longest Lived Control (LLC) group of all the experiments listed in this database. The LLC group was one of the control groups from reference 20, which lived an average of 34.3 months. The START column shows the age when treatment was begun. A ~ symbol means that a number was estimated. For animals that were calorically restricted, the amount of rat chow below ab libitum they were allowed to consume is indicated by the number before the word "chow". Thus -49% chow indicates that the animals were fed 49% less chow, than they would normally consume. Some experiments which restricted calories by feeding animals only every other day did not clearly indicate the extent of the reduction. This is indicated by "EOD" chow. An interesting variant on caloric restriction is to be found in reference 19. Here the animals were allowed to eat ad libitum of a chow that was diluted by cellulose. Strictly speaking they were not "restricted", since the caloric intake was reduced voluntarily. Some caloric restriction experiments fortified their chows so that restricted animals did not consume less protein, vitamins, and minerals than those fed ab libitum. This is indicated by the shorthand PR+, VIT+, and MIN+. Thus -49% chow PR+ VIT+ MIN+ means that 49% less chow (and calories) was consumed, but fortification with protein, vitamins, and minerals eliminated any potential confounding effects of multiple variations in the intake of these nutrients. %CHANGE REF TREATMENT START CONTROL LLC 7 acetaminophen 242 mg/l 9.4+ 2 -33 24 aluminum 10 mM 20.1+ -7 -17 29 antioxidents(beta carotene, 2+ 16 -24 ascorbic acid, alpha tocopherol, 9+ 13 -27 rutin, selenium, zinc) 16+ 4 -27 23+ 2 -22 1 ascorbic acid 1% drinking water 1.2+ 9 -9 7 aspirin 495 mg/l 8.1+ 0 -34 7 242 8.1+ -10 -41 7 113 8.1+-9.3+ 3 -32 4 beta carotene 0.5% 1+ 5 -13 4 0.5% 20.3+ -12 -22 25 brain damage 1+ 1 -18 6 butylated hydroxytoluene 0.5% 2.5+ 26 -18 6 0.2% 10+ 0 -12 7 chloropromazine 16.7 mg/l 9.7+-10.7+ 0 -34 7 chloroquine 39.5 mg/l 10.4+-12.1+ 0 -34 7 13.2 mg/l 9.4+-10.4+ -8 -40 7 chlorpheniramine 2.28 mg/l 9.4+ -2 -34 7 0.762 mg/l 9.4+-10.4+ 0 -34 8 coffee (in place of drinking water) 7+ ~-8 ~-21 8 (in place of drinking water) 4+ ~-17 ~-42 5 copper gluconate 5 mM 1+ -14 -24 5 1 mM 1+ -12 -24 5 0.5 mM 1+ -15 -26 26 -66% chow PR+ VIT+ MIN+ (30 C temp) 1+ 4 -21 26 -54% chow PR+ VIT+ MIN+ 1+ 47 11 23 -49% chow PR+ VIT+ MIN+ 1+ 48 -2 15 -44% chow PR+ VIT+ MIN+ 12+ 20 -13 20 -43% chow VIT+ MIN+ 0+ 12 -16 20 -43% chow VIT+ MIN+ 0+ -9 -9 20 -43% chow VIT+ MIN+ 0+ 5 -3 20 -43% chow VIT+ MIN+ 0.7+ -7 -30 20 -43% chow VIT+ MIN+ 0.7+ -9 -9 20 -43% chow VIT+ MIN+ 0.8+ -11 -17 20 -43% chow VIT+ MIN+ 1+ -1 -38 21 -40% chow VIT+ 1+ 15 -8 21 -40% chow VIT+ 1+ 24 -2 16 -33% chow 1+ 5 -21 28 -26% chow 12+ 16 1 28 -26% chow + dehydroepiandrosterone 12+ 13 -2 18 -25% chow 1+ -33 -43 19 -12.5% chow (50% cellulose) 16+ 8 -21 19 -12.5% chow (50% cellulose) 16+ 11 -16 19 -7.7% chow (33% cellulose) 16+ 5 -23 19 -7.7% chow (33% cellulose) 16+ 4 -22 20 EOD chow (during weaning) 0-0.7 25 -6 20 EOD chow (during weaning) 0-0.7 9 9 (longest lived control (LLC) group here lived 34.3 months average) 17 EOD chow 1.5+ 27 -8 17 EOD chow 6+ 11 -15 17 EOD chow 10+ 0 -21 12 EOD chow 25+ 0 -17 30 cotton seed oil 25% ? 1 -41 28 dehydroepiandrosterone 0.05 mg/day 12+ 2 -11 7 dimethylaminoethyl 8.1+-9.3+ 4 -32 chlorophenoxyacetate 13 exercise 12-24 ~0 ~-13 13 exercise 24+ ~-5 ~-15 14 exposure to 10 C decreases 27 ginkgo biloba (EGb 761 50 mg/day) 15+ 0 ? 30 lard 25% ? -9 -47 11 melatonin (night time) 19+ 17 -15 6 2-mercaptoethylamine HCL 1% 10+ 0 -12 6 1% 10+ 0 -18 9 methionine 50 mM 1.4+ ~-17 ~-26 9 50 mM 19.4+ ~0 ~-27 2 pantothenic acid 0.3 mg/day 1+ 18 -36 0.3 mg/day 1+ 20 -37 11 pineal grafting 16+ ~24 ~-24 12 protein 4 to 24% 25+ ~0 ~-15 22 -85% PR 1+ ~19 ~-18 3 pyridoxine HCL 100 mg/kg/day 18+ 11 ? 10 thiazolidine-4-carboxylate 23+ ~9 ~-9 -magnesium 0.07% 12 vitamin level NRC 4X 1+ 19 -28 12 4X 12+ 0 -22 12 4X 17+ 2 -19 12 4X 20+ 0 -24 12 vitamin level NRC 0.5X 1+ -57 -74 12 0.5X 12+ -23 -41 12 0.5X 17+ -18 -34 12 0.5X 20+ 1 -23 31 x-rays 4+ decreases SPECULATION: An outstanding effort (reference 26) by a research group led by Akio Koizumi has finally elucidated the primary mechanism for the life span increases associated with caloric restriction in C57BL/6J mice. Unlike humans who suffer greatly from the vissitudes associated with cardiovascular disease, C57BL/6J mice die primarily of lymphoma cancer. Also unlike humans, these mice readily experience torpor, especially when calorically restricted. These reductions in body temperature can be prevented by housing the mice at 30 C. Doing this virtually eliminates both the anti-lymphoma effect of caloric restriction, and its associated life span increases. Stated otherwise, it is body temperature that is the key determinate of longevity in C57BL/6J mice. (Please note that in order to equalize body weights the mice housed at 30 C had to have their food ration slightly reduced: -66% versus -54%.) The life span of the control groups varies widely, with the LLC group living longer than virtually all of the calorically restricted groups. It is apparent that calories are not the only factor influencing torpor. I speculate that small reductions in housing temperature while the animals are asleep may promote torpor, independantly of caloric intake. It would be interesting to see the results of chemically blocking cancer development in C57BL/6J mice, by adding powerful anticarcinogens such as curcumin to mouse chow. 1 "Dietary Vitamin C Improves the Survival of Mice" Gerontology 30: 371-375 1984 2 "Effect of Pantothenic Acid on the Longevity of Mice" Proceedings of the Society for Experimental Biology and Medicine 99(3): 632-633 December 1958 (note mice were referred to only as C57 black mice) 3 "Favorable Effects of Pyridoxine HCL on the Aging Process of C57BL/6J Mice" AGE 5(4): 143 October 1982 4 "Effect of Dietary B-Carotene on the Survival of Young and Old Mice" Gerontology 32: 189-195 1986 5 "Excessive Intake of Copper: Influence on Longevity and Cadmium Accumulation in Mice" Mechanisms of Ageing and Development 26: 195-203 1984 6 "Effect of Antioxidents on Life-Span of C57BL Mice" Journal of Gerontology 26(3): 378-380 1971 7 "Effects of Various Drugs on Longevity in Female C57BL/6J Mice" Gerontologia 19: 271-280 1973 8 "The Effects of Prolonged Coffee Intake on Genetically Identical Mice" Life Sciences 21(1): 63-70 1977 9 "The Effect of Dietary Methionine on the Copper Content of Tissues and Survival of Young and Old Mice" Experimental Gerontology 19: 393-399 1984 10 "Favorable Effects of the Antioxidents Sodium and Magnesium Thiazolidine Carboxylate on the Vitality and Life Span of Drosophilia and Mice" Experimental Gerontology 14: 279-285 1979 11 "The Pineal Control of Aging: The Effects of Melatonin and Pineal Grafting on the Survival of Older Mice" Annals of the New York Academy of Sciences" 621: 291-313 1991 12 "The Effect of Dietary Vitamin, Protein and Intake Levels on the Life Span of Mice of Different Ages" Age 8: 13-17 January 1985 13 "Effect of Exercise on Longevity, Body Weight, Locomotor Performance and Passive-Avoidance Memory of C57BL/6J Mice" Neurobiology of Aging 6: 17-24 1985 14 "A Longetudinal Study of Tolerance to Cold Stress Among C57BL/6J Mice Journal of Gerontology 40(1): 8-14 1985 15 "Dietary Restriction in Mice Beginning at 1 Year of Age: Effect on Life-Span and Spontaneous Cancer Incidence" Science 215: 1415-1418 1982 16 "Effects of Food Restriction on Aging: Separation of food Intake and Adiposity" Proc. Natl. Acad. USA 81: 1835-1838 1984 17 "Effects of Intermittent Feeding Upon Body Weight and Lifespan in Inbred Mice: Interaction of Genotype and Age" Mechanisms of Ageing and Development 55:69-87 1990 18 "Genetic Differences in Effects of Food Restriction on Aging in Mice" Journal of Nutrition 117: 376-382 1987 19 "Effect of Dietary Cellulose on Life Span and Biochemical Variables of Male Mice" Age 11(1): 7-9 1988 20 "Survival and Disease Patterns in C57BL/6J Mice Subjected to Undernutrition" Experimental Gerontology 15: 237-258 1980 21 "Longevity, Body Weight, and Neoplasia in Ad Libitum-Fed and Diet-Restricted C57BL/6J Mice Fed NIH-31 Open Formula Diet" Toxicologic Pathology 23(5): 570-582 1995 22 "Dietary Protein, Life-Span and Biochemical Variables in Female Mice" Journal of Gerontology 31(2): 144-148 1976 23 "Mitotic Activity in Mice is Suppressed by Energy Restriction-Induced Torpor" Journal of Nutrition 122: 1446-1453 1992 24 "Aluminum in the Organs and Diet of Ageing C57BL/6J Mice" Mechanisms of Ageing and Development 45: 145-156 1988 25 "Brain Damage, Stress and Life Span: An Experimental Study" Journal of Gerontology 37(2): 161-168 1982 26 "A Tumor Preventive Effect of Dietary Restriction is Antagonized by a High Housing Temperature Through Deprivation of Torpor" Mechanisms of Ageing and Development 92: 67-82 1996 27 "Effect of Long-Term Treatment With EGb 761 on Age-Dependent Structural Changes in the Hippocampi of Three Inbred Mouse Strains" Life Sciences 56(4): 213-222 1995 28 "Effect of Dehydroepiandrosterone Sulfate on Life-Span of Normally Fed and Calorically restricted C57BL/6 Mice" The Gerontologist 37(1): 7 1997 29 "The Prolongation of Survival in Mice by Dietary Antioxidents Depends on Their Age by the Start of Feeding This Diet" Mechanisms of Ageing and Development 92: 227-234 1996 30 "Osteoarthrosis in Mice Fed Diets Enriched With Animal or Vegetable Fat" Archives of Pathology 70: 119-124 1960 31 "Chemical Protection of the Mouse Against Radiation-Induced Life Shortening" Radiation Research 47: 537-547 1971 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=9157