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Biomedical subjects

H R Massie

Publications and source records attributed to H R Massie.

At least 19 recordsLinked to original sources

Lead accumulation in the bones of aging male mice.

The lead content of mouse femurs increased by 83% between 76 and 958 days of age with values ranging from 0.192 to 1.78 ng Pb/mg dry weight. These values are remarkably lower than in previous reports for the lead content of bone. The lead content of mouse liver showed no aging-related trend with values ranging from 0.00823 to 0.0149 ng/mg dry weight. Bone density, calcium and collagen content were not related to the lead content. We conclude that while bone lead content is very low in mice, it increases with aging but does not appear to be related to the osteopenia which develops in the C57BL/6J male mouse.

Aging

Preliminary evidence for photochemical ageing in Drosophila.

Drosophila melanogaster (Oregon R) males were exposed to visible light intensities varying from 0.3 to 7300 lux at environmental temperatures of 30, 35 and 37 degrees C, on a 12-h light/dark diurnal rhythm. At 30 degrees C reducing the light exposure from 7300 to 4 lux increased the median life span by 141%. At 35 degrees C reducing the light exposure from 4650 to 0.3 lux increased the life span by 389%. At 37 degrees C a reduction from 6580 to 0.3 lux increased life span by 453%. Even dim light (65 lux) affected life span in a negative manner. Two phases of response to light were identified, with a slow change in life span occurring below 400 lux and a more rapid rate of change above 400 lux. We conclude that visible light may be a major factor in the ageing process for Drosophila and that photochemical effects may contribute to senescence in other organisms. Possible alternative reasons for the effect of light on the life span of Drosophila include changes in body temperature, physical activity and oxygen consumption.

Aging

Ascorbic acid in Drosophila and changes during aging.

The ascorbic acid content of Drosophila melanogaster was found to be high in the absence of a dietary source. The amount of ascorbic acid per fly declined with aging in both the Oregon R and Swedish C strains. The median life span at 25 degrees C was 45 days for Swedish C and 59 days for Oregon R. The amount of ascorbic acid in Swedish C flies (0.078 micrograms/fly) was higher than that for Oregon R (0.058 micrograms/fly) for newly emerged flies but the rate of decline with aging was greater for Swedish C than Oregon R. The decline in ascorbic acid content with aging was 70.4% for Swedish C versus 19.9% for Oregon R. A brief cold shock was found to significantly increase the amount of ascorbic acid in Oregon R flies. Feeding the precursor of ascorbic acid synthesis, L-gulonolactone, did not improve the life span. Life-time feeding of ascorbic acid did not improve the life span of either Swedish C or Oregon R flies.

Aging

Uric acid content of Drosophila decreases with aging.

Free uric acid concentrations declined with aging in male Oregon R Drosophila melanogaster by 59% or more between 0 and 50 days of adult age. Free xanthine concentrations increased between 0 and 5 days of age and declined by 75% between 5 and 50 days of age. Xanthine oxidase activity was maximal for newly emerged flies and then declined rapidly reaching a minimum at 9 days of age. After 9 days of age xanthine concentrations may be the limiting factor for the production of uric acid by xanthine oxidase in aging fruit flies. Declining uric acid concentrations may represent a loss of antioxidant potential in aging Drosophila.

Aging

Changes in boron concentration during development and ageing of Drosophila and effect of dietary boron on life span.

Total boron concentrations in Drosophila changed during development and ageing. The highest concentration of boron was found during the egg stage followed by a decline during the larval stages. Newly emerged flies contained 35.5 ppm boron. During the adult stage the boron concentration increased by 52% by 9 weeks of age. Adding excess dietary boron during the adult stage decreased the median life span by 69% at 0.01 M sodium borate and by 21% at 0.001 M sodium borate. Lower concentrations gave small but significant increases in life span. Supplementing a very low boron diet with 0.00025 M sodium borate improved life span by 9.5%. The boron contents of young and old mouse tissues were similar to those of Drosophila and human samples. We conclude that moderate levels of dietary boron may have a general protective effect in biological systems. The mechanism of this effect at present remains unknown.

Aging

Calcium, iron, copper, boron, collagen, and density changes in bone with aging in C57BL/6J male mice.

X-rays of old C57BL/6J male mice showed deformed vertebral columns. Bone density was found to increase between 76 and 517 days of age and to decrease after 685 days of age. The boron content of femurs declined by 9% with aging but the decrease was not significant. Calcium increased between 76 and 198 days of age but declined by 36% between 200 and 1000 days of age. Iron increased by 207% by 1000 days of age. Copper declined between 76 and 198 days of age but increased by 61% between 200 and 1000 days of age. Bone collagen as indicated by hydroxyproline and proline content decreased 17.4% by 1000 days of age. The largest single change with aging was, therefore, in the iron content of bone. Several correlations were found to be independent of the age of the animals. Bone density was correlated with bone calcium and collagen. Iron was negatively correlated with calcium and collagen. Calcium and collagen content were unrelated. Bone density and iron were also surprisingly unrelated. A possible explanation for this observation is given. Copper was negatively correlated with bone calcium, bone density, and collagen content. Excess copper was, therefore, the single most important factor associated with decreasing bone size and density.

Aging

Changes in taurine in aging fruit flies and mice.

The whole-body concentration of the amino acid taurine was found to be more than 1000% higher during the adult stage of Drosophila melanogaster than during the larval stage. Drosophila larvae were killed by adding taurine (0.01 to 0.10 M) to their food medium. Adult Drosophila failed to produce progeny when fed 0.2 M taurine for one week. Lifetime feeding of taurine (0.05 to 0.20 M) produced no change in life span. Feeding the taurine precursor, hypotaurine, and the taurine mobilizing agent, beta-alanine, to Drosophila did not change life span at low concentrations but both decreased life span at higher concentrations. Taurine concentration in male C57BL/6J mice increased with aging in the heart, decreased in leg muscle and remained unchanged in brain, liver, kidney, and blood. We suggest that an as yet undefined developmental process is altered in Drosophila by taurine and that this process may be unique to insects.

Aging

Calcium and calmodulin changes with ageing in C57BL/6J mice.

Male C57BL/6J mice ranging in age from 50 to 1186 days were used to measure total calcium and calmodulin concentrations. The increase in calcium between 0 and 1,000 days of age was 260% for kidney, followed by brain (189%), heart (173.5%), lung (106.5%) and liver (78.5%). Calcium in femur declined by 28.2%. The calmodulin content of liver increased with ageing. Both liver and kidney calmodulin concentrations declined early in life followed by ageing-related increases. Brain, lung and heart calmodulin concentrations did not change significantly with ageing. We conclude that changes in calcium homeostasis are not reflected in calmodulin changes. The loss of calcium in bone is consistent with the occurrence of osteoporosis in ageing C57 mice.

Aging

Aluminum in the organs and diet of ageing C57BL/6J mice.

Total aluminum concentrations increased with ageing in the liver and kidney of male C57BL/6J mice, remained unchanged in brain and heart, and decreased with ageing in femur and lung for mice ranging in age from 56 to 1186 days. Ligating one kidney did not significantly increase aluminum concentrations in the various organs. Feeding 1 X 10(-2) M aluminum chloride (270 ppm Al) in the drinking water beginning at 604 days of age decreased the average life span by 6.7%. We conclude that very little aluminum accumulation occurs with ageing in the organs tested in this study, in spite of a high dietary intake. Other organs might show a change. Only one aluminum concentration was used in this study which accelerated the rate of ageing as indicated by a change in the survival curve. The effect of higher or lower aluminum concentrations remains to be seen.

Aging

Influence of age on mitochondrial enzyme levels in Drosophila.

The specific activity and the activity per fly of four mitochondrial enzymes did not change with ageing in male Drosophila melanogaster (Oregon R). The enzymes assayed were rotenone-insensitive NADH-cytochrome c reductase, adenylate kinase, succinate cytochrome c reductase, and malate dehydrogenase, located in the outer membrane, inner membrane space, inner membrane and matrix, respectively. The specific activity of malate dehydrogenase showed no significant change for young and old head, thorax and abdomen. We conclude that there is no specific site for ageing damage in the mitochondrion, when the enzyme activities in this study are used as an indicator. It should be noted, however, that these enzymes represent only a small percentage of the total enzymes present in mitochondria.

Adenylate Kinase

Mitochondrial DNA and life span changes in normal and dewinged Drosophila at different temperatures.

At 11 and 30 degrees C there was no change in the amount or in the buoyant density of nuclear DNA of male Oregon R Drosophila melanogaster with aging. When normal flies were maintained at 11 degrees C (at which temperature they do not fly), mitochondrial DNA content declined gradually with aging and 39.4% of the original mitochondrial DNA was lost at the median survival time of 152 days of age. For normal flies maintained at 30 degrees C, 86.5% of the mitochondrial DNA was lost during aging at the median survival time of 25 days. In contrast only a 39.2% decrease in the mitochondrial DNA occurred in dewinged flies maintained at 30 degrees C. A slow phase of mitochondrial DNA loss appears to be related to aging and a fast phase to flight activity. Removing the wings of flies eliminates the fast phase of DNA loss but only slightly improves life span (by less than 10%). Lowering the environmental temperatures to 11 degrees C also eliminates fast phase DNA loss and decreases the rate of the slow phase DNA loss. We conclude that mitochondrial DNA loss is related to both physical activity and to the aging process itself.

Aging

Effect of dietary beta-carotene on the survival of young and old mice.

Feeding 0.5% beta-carotene in the diet for life beginning at 29 days of age improved the average life span of C57BL/6J male mice by 5.0% but decreased the life span of mice started at 608 days of age by 11.5%. Neither difference, however, proved to be statistically significant. Feeding beta-carotene increased the concentration of beta-carotene in the serum by 60% but did not change the beta-carotene content of heart, liver or kidney. We conclude that singlet oxygen, which is very efficiently quenched by beta-carotene, is an important factor in senescence only if it is produced at organ sites not accessible to serum beta-carotene. Since we have found that beta-carotene feeding is not a useful means for increasing tissue concentrations of beta-carotene, other more sophisticated means must be developed for accomplishing this purpose. It is also clear that while dietary beta-carotene is not an effective means for prolonging life span, it is nontoxic when fed continuously at high concentrations.

Absorption

Iron accumulation during development and ageing of Drosophila.

We examined Drosophila melanogaster fruit flies to determine whether iron accumulates with ageing as it does in mice. Iron concentrations were measured by atomic absorption for flies maintained at 11, 20, 25 and 30 degrees C where the average lifespans were 152, 81, 62 and 25 days, respectively. Iron was found to accumulate with ageing during both the adult and developmental stages with an overall increase of 186% at 25 degrees C. A similar increase was found at 20 degrees C and 30 degrees C. At 11 degrees C the increase was less than half that at 25 degrees C. The rate of iron accumulation also varied with environmental temperature with the logarithm of the rate proportional to temperature (log R = 0.0509T-0.384). The rate of iron accumulation with ageing was, thus, found to be proportional to the rate of ageing, suggesting that excess dietary iron may be an initiator of senescence.

Aging

Influence of anti-inflammatory agents on the survival of Drosophila.

Various anti-inflammatory compounds were tested for their influence on the life span of the fruit fly (Drosophila melanogaster). 2,3-dihydroxybenzoic acid increased the median life span by 10.9% when fed to adults at a concentration of 1 X 10(-5)M for the entire adult life span. All other anti-inflammatory compounds including acetylsalicylic acid, acetylsalicylic acid plus cupric chloride, Bufferin, chlorpromazine HC1, dimethylsulfoxide, indomethacin, phenol, salicylic acid, and sodium salicylate either decreased or did not change the life span. Rearing flies on 0.5% (0.060M) dimethylsulfoxide caused a 33.3% reduction in life span compared with an 11.8% reduction when fed during adulthood only. At low doses all of the anti-inflammatory compounds including dimethylsulfoxide proved to be nontoxic as measured by changes in life span.

Aging

Excess dietary aluminum increases Drosophila's rate of aging.

Aluminum concentrations in the whole organism increased during development and aging of Drosophila melanogaster. The amount of aluminum in the flies was also reflected by the dietary content of aluminum. Additional dietary aluminum, in the form of aluminum salts, decreased the life span by as much as 20%. A significant reduction in life span was found for 1 X 10(-4) M aluminum chloride and for 1 X 10(-3) M aluminum nitrate and aluminum sulfate. Dietary sodium fluoride failed to increase life span.

Aging

Excessive intake of copper: influence on longevity and cadmium accumulation in mice.

Feeding copper gluconate in the drinking water to C57BL/6J male for a lifetime decreased the mean survival times by 14.4% when given at a concentration of 5 X 10(-3) M (317 ppm copper). The maximum life span was reduced by 12.8% (from 986 to 874 days). Survival data at lower copper concentrations are also reported. Serum, brain, heart and kidney copper concentrations were unaltered by feeding 5 X 10(-3) M copper gluconate. Only liver concentrations increased. Cadmium concentrations in liver and kidney of 168-, 406- and 644-day-old mice were essentially unchanged after feeding copper gluconate for 104 days. We conclude that chronic consumption of copper does not prevent or reduce the normal accumulation of cadmium found in aging mice.

Aging

The effect of dietary methionine on the copper content of tissues and survival of young and old mice.

We tested the possibility that methionine might improve the lifespan of male C57BL/6J mice, based upon the ability of methionine to chelate copper. Old mice given 0.05M methionine in their drinking water for 42 days had lower brain copper concentrations (p less than 0.05). The decrease in liver, kidney, and heart copper was not significant when compared to unsupplemented controls. The lifespan of old mice was unchanged by feeding 0.05M methionine. Young mice, however, experienced a 16.9% decrease in their average lifespan and a decreased maximum lifespan when given supplemental methionine. We conclude that dietary supplements of methionine may be useful for removing copper from the brain but they also can increase the rate of senescence in mice.

Aging