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.
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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