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Biomedical subjects

V R Aiello

Publications and source records attributed to V R Aiello.

At least 19 recordsLinked to original sources

Inhibition of iron absorption prolongs the life span of Drosophila.

The life span of Drosophila melanogaster (Oregon R) males was found to be proportional to the logarithm of the iron content of the diet. Life span was also shown to be proportional to the rate of iron accumulation for Drosophila, mice and man. The total body iron content was found to correlate with the total calcium content of adult Drosophila. Iron content during the developmental stages, however, remained relatively constant and did not change with changes in the calcium concentrations. Dietary tea (Camellia sinensis) extracts were found to inhibit the ageing-related accumulation of iron and to prolong the life span of Drosophila by as much as 21.4%. It is concluded that iron accumulation is a significant factor contributing to senescence.

Absorption↗

Influence of photosensitizers and light on the life span of Drosophila.

The life span of adult Drosophila melanogaster fruit flies changed when they were fed two different photosensitizers. Methylene blue decreased the median life span by 49% when present in the food at a concentration of 0.001 M. Another photosensitizer, riboflavin, produced no changes in life span under the same conditions of a 12:12 h light/dark cycle at a daytime light intensity of 1000 lux. Flies exposed to constant darkness lived 43.2% longer than those exposed to constant light at a light intensity of 2000 lux. Under these conditions, riboflavin increased the life span of the flies exposed to constant light by as much as 25%. We conclude that riboflavin confers some degree of protection against the effects of constant light exposure. The completely different results obtained with riboflavin and methylene blue suggest a possible mechanism for photoageing involving photodynamic action mediated through the production of singlet oxygen.

Animals↗

Elevated serum copper is associated with reduced immune response in aging mice.

Young mice were found to have serum copper concentrations ranging from a low of 0.291 to a high of 0.584 ppm. Old mice had serum copper concentrations ranging from 0.223 to 1.715 with 30.9% of the old animals having values greater than 0.6 ppm. The mitogen response of isolated lymphocytes from the spleens of aging mice was greatly reduced when these cells were taken from animals with naturally occurring serum copper levels in excess of 0.6 ng of copper/mg wet weight serum. The lymphocytes taken from young mice with higher serum copper concentrations, on the other hand, had increased response to mitogens. Addition of the copper protein, ceruloplasmin, to lymphocyte cultures in vitro reduced the mitogen response of purified splenic lymphocytes with the reduction being greater for cells from old animals. We suggest that excess serum copper and ceruloplasmin may be immunosuppressive, especially in older organisms.

Aging↗

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↗

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↗

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↗

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↗

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↗

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↗

Influence of dietary copper on the survival of Drosophila.

The life span of Drosophila melanogaster was reduced when copper compounds were fed at concentrations of 1 X 10(-3) M or greater. Feeding lower concentrations of copper compounds failed to significantly change life span. A combination of copper gluconate and gluconic acid increased the adult life span by 21.6%. We conclude that only an extraordinarily high dietary intake of copper would accelerate senescence. Dietary gluconic acid retarded the normal age-related accumulation of copper in adult flies.

Animals↗

Dietary vitamin C improves the survival of mice.

Feeding C57BL/6J male mice 1% ascorbic acid (1,430 mg/kg body weight) in their drinking water for life increased the average life span by 8.6% (p less than 0.05) and perhaps by as much as 20.4%. The ascorbic acid group weighed 6-7% less than the control group up until 800 days of age. The maximum life span for the control group was 965 days and 993 days for the ascorbic acid group, representing an increase of only 2.9% in the maximum life span. The copper content of heart, liver, kidney, and brain was unchanged after feeding 1% ascorbic acid for 48 days. The copper content of heart declined by 20.4% after feeding 2% ascorbic acid. Liver, kidney, and brain were unchanged.

Animals↗

Iron accumulation and lipid peroxidation in aging C57BL/6J mice.

Total iron concentrations in organs from C57BL/6J male mice increased with age. In animals ranging 45 to 900 days of age liver iron increased by 216%, heart by 66%, kidney by 54% and brain by 27%. Two separate phases of iron accumulation were found in brain, kidney and liver. Between 45-355 days of age brain iron increased by 33% and after 355 days there was no change. For both kidney and liver no change was found until after 355 days of age when liver increased by 140% and kidney by 44%. The kidney and liver results suggest a true aging phenomenon. Liver peroxidation potential as measured by the thiobarbituric acid test tended to increase with age but the differences were not significant. The addition of metal ion chelators greatly reduced lipid peroxide values for all organs but no significant age-related trend was evident. We conclude that the large aging-related increases in tissue iron are not correlated with increased concentrations of lipid peroxides.

Aging↗

Influence of dietary cadmium and chelators on the survival of Drosophila.

Dietary cadmium chloride at concentrations of 1 X 10(-4) M or greater shorten the life span of Drosophila melanogaster by as much as 74%. The chelator, CDTA, inhibits the normal age-related cadmium accumulation in whole flies and also improves the median life span by 20%. These data are interpreted to indicate that dietary cadmium may be a determining factor for the onset of senescence.

Aging↗