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Fleming, J.

Publications and source records attributed to Fleming, J..

Effects of simulated increased gravity on the rate of aging of rats - Implications for the rate of living theory of aging

It was found that the rate of aging of 17 month old rats which had been exposed to 3.14 times normal gravity in an animal centrifuge for 8 months was larger than that of the controls as determined by the apparently elevated lipofuscin content in heart and kidney, reduced numbers and increased size of mitochondria of heart tissue, and inferior liver mitochondria respiration. Steady-state food intake per day per kg body weight, which is presumably proportional to rate of living or specific basal metabolic expenditure, was found to be about 18 percent higher than in the controls after an initial 2 month adaptation period. Although half of the centrifuged animals lived only a little shorter than the controls (average about 343 vs. 364 days on the average, statistically nonsignificant), the remaining half (longest survivors) lived on the centrifuge an average of 520 days (range 483-572) compared to an average of 574 days (range 502-615) for the controls, computed from the onset of centrifugation, or 11 percent shorter. These findings indicate that a moderate increase of the level of basal metabolism of young adult rats adapted to hypergravity compared to controls in normal gravity is accompanied by a roughly similar increase in the rate of organ aging and reduction of survival, in agreement with Pearl's (1928) rate of living theory of aging, previously experimentally demonstrated only in poikilotherms.

Economos, A. C.↗

Antioxidants, metabolic rate and aging in Drosophila

The metabolic rate-of-living theory of aging was investigated by determining the effect of several life-prolonging antioxidants on the metabolic rate and life span of Drosophila. The respiration rate of groups of continuously agitated flies was determined in a Gilson respirometer. Vitamin E, 2,4-dinitrophenol, nordihydroguaiaretic acid, and thiazolidine carboxylic acid were employed as antioxidants. Results show that all of these antioxidants reduced the oxygen consumption rate and increased the mean life span, and a significant negative linear correlation was found between the mean life span and the metabolic rate. It is concluded that these findings indicate that some antioxidants may inhibit respiration rate in addition to their protective effect against free radical-induced cellular damage.

Miquel, J.↗

Mitochondrial role in cell aging

The experimental studies on the mitochondria of insect and mammalian cells are examined with a view to an analysis of intrinsic mitochondrial senescence, and its relation to the age-related changes in other cell organelles. The fine structural and biochemical data support the concept that the mitochondria of fixed postmitotic cells may be the site of intrinsic aging because of the attack by free radicals and lipid peroxides originating in the organelles as a by-product of oxygen reduction during respiration. Although the cells have numerous mechanisms for counteracting lipid peroxidation injury, there is a slippage in the antioxidant protection. Intrinsic mitochondrial aging could thus be considered as a specific manifestation of oxygen toxicity. It is proposed that free radical injury renders an increasing number of the mitochondria unable to divide, probably because of damage to the lipids of the inner membrane and to mitochondrial DNA.

Miquel, J.↗