X-Message-Number: 8666
Date: Fri, 10 Oct 1997 17:52:55 -0700 (PDT)
From: Doug Skrecky <>
Subject: Long-Evans Rat Longevity Database
LONG-EVANS RAT LONGEVITY DATABASE
(Updated by Doug Skrecky October 10,1997)
This is a database listing the effect of various treatments on the
average longevity of Long-Evans rats. The percent change in average life
span is listed under the %CHANGE columns, relative to either the CONTROL
group used in the experiment, or to the Longest Lived Control (LLC) group
of all the experiments listed in this database. The LLC group was one of
the control groups used in reference #10, which lived an average of 32.6
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
just before the word "chow". Thus -33% chow indicates that the animals
were fed 33% less chow, than they would normally consume. One exception
to this is in reference 14, where the control rats were themselves mildly
restricted by 8%. Note that some animals consumed additional chow, when
they were either exercised or exposed to cool water.
%CHANGE
REF TREATMENT START CONTROL LLC
2 aluminum 5 ppm 1+ -2 -9
2 aluminum 5 ppm 1+ 2 -12
12 potassium ANTIMONY tartrate 5 ppm ~1+ -12 -22
12 potassium ANTIMONY tartrate 5 ppm ~1+ -12 -18
11 sodium ARSENITE 5 mg/l & chromium 1 mg/l ~1+ -5 -16
11 sodium ARSENITE 5 mg/l & chromium 1 mg/l ~1+ 0 -7
2 Barium 5 ppm 1+ -17 -23
2 barium 5 ppm 1+ -7 -20
2 beryllium 5 ppm 1+ -5 -12
2 beryllium 5 ppm 1+ 6 -9
10 cadmium acetate 5 ppm ~1+ -16 -16
10 cadmium acetate 5 ppm ~1+ -15 -18
13 +44 chow + 23 C water 20 hrs/week 6+ 5 -1
15 +20% chow & exercise 4+ 9 3
5 -8% chow 6+ 1 -5
5 -8% chow & exercise 6+ 10 3
14 -24% chow 3+ 21 8
14 -24% chow & exercise 3+ 14 2
5 -28% chow 6+ 21 14
7 -33% chow 18+ decreases
14 -42% chow 3+ 24 11
10 chromium acetate 5 ppm ~1+ -6 -6
10 chromium acetate 5 ppm ~1+ 1 -3
1 chromium chloride 1 mg/kg diet ~1+ 7
1 chromium dinicotinate 1 mg/kg diet ~1+ 7
1 chromium picolinate 1 mg/kg diet ~1+ 35
14 exercise 3+ 12 0
11 sodium GERMANATE 5 mg/l & chromium 1 mg/l ~1+ -15 -25
11 sodium GERMANATE 5 mg/l & chromium 1 mg/l ~1+ -9 -15
10 lead acetate 5 ppm ~1+ -25 -25
10 lead acetate 5 ppm ~1+ -23 -26
12 lead nitrate 25 ppm ~1+ 1 -10
3 nickel 5 ppm 1+ 0 -12
3 nickel 5 ppm 1+ 6 -6
12 sodium NIOBATE 5 ppm ~1+ 2 -9
12 sodium NIOBATE 5 ppm ~1+ 9 2
4 selenate 2 ppm ~1+ 13 -2
4 selenate 2 ppm ~1+ 16 4
4 selenite 2 ppm ~1+ -93 -94
4 selenite 2 ppm ~1+ -60 -64
11 stannous chloride 5 mg/l & chromium 1 mg/l ~1+ 0 -11
11 stannous chloride 5 mg/l & chromium 1 mg/l ~1+ -9 -15
9 sugar, brown & vit E deficiency ~1+ -8 -18
9 sugar, brown & vit E deficiency ~1+ -14 -20
9 sugar, raw & vit E deficiency ~1+ -22 -30
9 sugar, raw & vit E deficiency ~1+ -23 -29
9 sugar, white & vit E deficiency ~1+ -15 -24
9 sugar, white & vit E deficiency ~1+ -32 -40
9 sugar, white & vit E deficiency ~1+ -27 -32
9 sugar, white & vit E deficiency ~1+ -31 -36
9 sugar, white, chromium 5ppm & E deficiency ~1+ -31 -39
9 sugar, white, chromium 5ppm & E deficiency ~1+ -30 -35
8 tansy ragwort 2.5% -87
8 tansy ragwort 2.5% & braken 10% -86
8 tansy ragwort 2.5% & St John's Wort 5% -87
8 tansy ragwort & braken & St John's Wort -83
4 tellurite 2 ppm ~1+ 1 -14
4 tellurite 2 ppm ~1+ 4 -7
6 -60% trytophan 0.7+ 0 -29
6 -70% trytophan 0.7+ -71 -80
2 tungsten 5 ppm 1+ -9 -16
2 tungsten 5 ppm 1+ 7 -8
12 vanadyl sulfate 5 ppm ~1+ -1 -12
12 vanadyl sulfate 5 ppm ~1+ 5 2
12 zirconium sulfate 5 ppm ~1+ 1 -10
12 zirconium sulfate 5 ppm ~1+ 4 -3
SPECULATION:
From this database the most interesting treatment is chromium
picolinate supplementation. This was added to a chromium replete rat chow
at a dosage of 1 mg/kg of chromium. Since standard low fat chow has a
caloric density of about 4 cals/gm, a human consuming 2400 calories per
day of this chow would be ingesting 600 mcg of chromium.
Long-Evans rats are a model of moderate adult onset diabetes. At 200
days of age plasma glucose of rats fed extra chromium picolinate,
chromium nicotinate or chromium chloride were 6.6, 7.7, and 7.8 mM. At
1000 days plasma glucose was 6.5, 8.3, and 8.2 mM. So only the picolinate
salt prevented age-associated hyperglycemia. Please note that this was
only a pilot experiment using just 10 animals per group. It was reported
only in abstract form, but subsequently further details were provided by
Mark McCarty. (1)
In humans hyperglycemia is associated with elevated mortality rates
and reduced life spans, so preventing this in rats this may account for
longevity prolonging effect of chromium picolinate.
The greatest maximum life span was 46.6 months for one of two control
groups from reference 10. However the maximum life span for some of the
treated groups was even longer. The treated groups with the greatest
maximum life spans are as follows:
REF INTERVENTION MAXIMUM AVERAGE
4 selenate 2 ppm 61 months 33.8 months
10 sodium arsenite 5 mg/l & chromium 1 mg/l 53.2 27.5
6 -70 tryptophan 50.9 6.7
2 beryllium 5 ppm 48.8 29.7
14 -24% chow & exercise 48.1 33.2
1 chromium picolinate 1 mg/kg 48 44
10 control group 46.6 31.5
What can we humans expect if the results in Long-Evans rats hold up in
humans? Comparing the maximal control group life span of 46.6 months with
95 human years, translates the 44 months for the chromium picolinate
group to an equivalent of 90 human years. However since most Long-Evans
rats become diabetic and thus live much shorter lives than they should,
then perhaps it is the 61 month old selenate doped rat that should be
equated with a 95 year old human. Here the average life span of 44 months
translates to 69 human years, which is a respectible, but not exceptional
figuare. Why does the LLC group live only 32.6 months, when much longer
life spans are possible?
The glycemic index (GI) or rate that glucose is absorbed from food is
known to determine the rate that rodents develop hyperglycemia with age.
(16) Standard rat chow has a high GI, and that may be the reason why
Long-Evans develop hyperglycemia and live short lives. Even a small
change in GI of chow is now known to alter both average and maximum life
span of rodents. (17) I speculate here that if fed a sufficiantly low GI
chow featuring whole grains, instead of high GI flour or starch, that
control rats might live as long as those given chromium picolinate. The
standard protein used was casein, which is now also known to decrease
rodent life span. (18) Replacing this with soy protein increases life
span, and I suspect using whole cooked soybeans might be even more
beneficial.
The results from all the other treatments are uninspiring. Selenate
showed a slight increase, as does exercise and life long caloric
restriction. The later may have been hampered by the finding that caloric
restriction imposed gradually starting at 18 months of age actually
decreased life span. (7) As a practical method for increasing human life
span, both selenate and caloric restriction get low marks, because of the
risk of toxicity. In humans it has been found that after physical fitness
is controlled for, that body weight has no effect on mortality, thus
strongly suggesting that caloric intake is NOT a significant modulator of
human aging. (19)
Moderate exercise gets high marks, and it is this plus consuming a low
GI diet and (possibly) chromium picolinate and biotin supplementation
that can be recommended. Note: Biotin at a dosage of 9 to 16 mg/day has
been found to be effective in treating hyperglycemia in both insulin
dependant & non-insulin dependant human diabetics. (20,21) Chromium
picolinate at a dosage of 1000 mcg/day has been found to be much more
effective than 200 mcg/day in the treatment of Chinese non-insulin
dependant diabetics. (22)
1 McCarty MF.
"Longevity Effect of Chromium Picolinate - 'Rejuvenation' of
Hypothalmic Function"
Medical Hypotheses 43: 253-265 1994
(corrections: The maximum life span of Long Evans rats was
here incorrectly stated to be 42 months. Also the quoted
submitted reference 2 was never published)
(but also see)
Evans GW, and Meyer L.
"Chromium Picolinate Increases Longevity"
Age 15: p134 abstract 51 1992
2 Schroeder HA, and Mitchener M.
"Life-term Studies in Rats: Effects of Aluminum, Barium, Beryllium
and Tungsten"
Journal of Nutrition 105: 421-427 1975
3 Schroeder HA, Mitchener M and Nason AP.
"Life-term Effects of Nickel in Rats: Survival, Tumours, Interactions
With Trace Elements and Tissue Levels"
Journal of Nutrition 104: 239-243 1974
4 Schroeder HA, and Mitchener M.
"Selenium and Tellurium in Rats: Effect on Growth, Survival and
Tumours"
Journal of Nutrition 101: 1531-1540 1971
5 Holloszy, JO, Smith EK, Vining M, and Adams S.
"Effect of Voluntary Exercise on Longevity of Rats"
J. Appl. Physiol. 59(3): 826-831 1985
6 Ooka H, Segall PE, and Timiras PS.
"Histology and Survival in Age-Delayed Low-Tryptophan Fed Rats"
Mechanisms of Ageing and Development 43: 79-98 1988
7 Lipman RD, Smith DE, Bronson RT, and Blumberg J.
"Is Late-Life Caloric Restriction Beneficial?"
Aging Clin. Exp. Res. 7: 136-139 1995
8 Garrett BJ, Cheeke PR, Cristobal LM, Goeger DE, and Buhler DR.
"Consumption of Poisonous Plants (Senecio Jacobaea, Symphytum
Offinciale, Pteridum Aquilinum, Hypericum Perforatum) in Rats:
Chronic Toxicity, Mineral Metabolism, and Hepatic Drug-Metabolizing
Enzymes"
Toxicology Letters 10: 183-188 1982
9 Schroeder HA, Mitchener M, and Nason AP.
"Influence of Various Sugars, Chromium and Other Trace Metals on
Serum Cholesterol and Glucose of Rats"
Journal of Nutrition 101: 247-258 1971
10 Schroeder HA, Balassa JJ, and Vinton Jr. WH.
"Chromium, Cadmium and Lead in Rats: Effects on Life Span, Tumours
and tissue Levels"
Journal of Nutrition 86: 51-66 1965
11 Schroeder HA, Kanisawa M, Frost DV, and Mitchener M.
"Germanium, Tin and Arsenic in Rats: Effects on Growth, Survival,
Pathological Lesions and Life Span"
Journal of Nutrition 96: 37-45 1968
12 Schroeder HA, Mitchener M and Nason AP.
"Zirconium, Niobium, Antimony, Vanadium and Lead in
Rats: Life Term Studies"
Journal of Nutrition 100: 59-68 1970
13 Holloszy JO, and Smith EK.
"Longevity of Cold-Exposed Rats: A Reevaluation of
the "Rate-of-Living" Theory"
J. Appl. Physiol. 61(5): 1656-1660 1986
14 Holloszy JO, and Schechtman KB.
"Interaction Between Exercise and Food Restriction:
Effects on Longevity of Male Rats"
J. Appl. Physiol. 70(4): 1529-1535 1991
15 Holloszy JO.
"Exercise Increases Average Longevity of Female Rats
Despite Increased Food Intake and no Growth Retardation"
Journal of Gerontology 48(3): B97-B100 1993
16 Higgins JA, Brand Miller JC, and Denyer GS.
"Development of Insulin Resistance in the Rat is Dependent
on the Rate of Glucose Absorption From the Diet"
Journal of Nutrition 126: 596-602 1996
17 Mlekusch W, Lamprecht M, Ottl K, Tillian M, and Reibnegger G.
"A Glucose-rich Diet Shortens Longevity of Mice"
Mechanisms of Ageing and Development 92: 43-51 1996
18 Iwasaki K, Gleiser CA, Masoro EJ, McMahan CA, Seo EJ, and Yu BP.
"The Influence of Dietary Protein Source on Longevity and
Age-Related Disease Processes of Fisher Rats"
Journal of Gerontology 43(1): B5-B12 1988
19 Barlow CE, Kohl HW, Gibbons LW, and Blair SN.
"Physical Fitness, Mortality, and Obesity"
International Journal of Obesity 19(Suppl 4): S41-S44 1995
20 Coggeshall JC, Heggers JP, Robson MC, and Baker H.
"Biotin Status and Plasma Glucose in Diabetes"
Annals of the New York Academy of Sciences 447: 389-392 1985
21 Maebashi M, Makino Y, Furukawa Y, Ohinata K, Kimura S, and Sato T.
"Therapeutic Evaluation of the effect of Biotin on Hyperglycemia
in Patients With Non-Insulin Dependant Diabetes Mellitus"
Journal of Clinical Biochemistry Nutrition 14: 211-218 1993
22 McCarty MF.
"Exploiting Complementary Therapeutic Strategies for the Treatment
of Type II Diabetes and Prevention of its Complications"
Medical Hypotheses 49: 143-152 1997
(Note the low dose of chromium was quoted as 299 mcg/day. This
is a misprint, and the correct figuare should be 200 mcg/day)
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