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W D Denckla

Publications and source records attributed to W D Denckla.

At least 19 recordsLinked to original sources
PubMed1980

Age-associated changes in initiation of ribonucleic acid synthesis in isolated rat liver nuclei.

Initiation of RNA synthesis was studied in an attempt to determine a possible molecular mechanism for age-related biochemical and physiological changes. Initiation of RNA synthesis was determined by incorporation of [gamma-32 P]ATP and of [gamma-32P]GTP into an acid-insoluble product by intact nuclei isolated from livers of Sprague-Dawley CD-strain rats of various ages. When the rats were grouped into young (0.75-9 months) and old (12-30 months) rats, a significant decrease (P less than or equal to 0.001) in incorporation of initiating nucleotides was observed. The rat population was divided into five age groups (0.75-3 months, 4-9 months, 12-18 months, 19-23 months and 30 months) for further analysis of the effect of age on the initiation of RNA synthesis. Analysis of data from these groups indicated a significant trend for an age-related decrease in RNA-synthesis initiation (correlation coefficient = 0.94). Long-term hypophysectomy coupled with minimal hormone-replacement therapy was shown to have a significant effect on the reversal of the age-related decrease in initiation of RNA synthesis. It was observed that initiation of RNA synthesis in nuclei from 19-month-old rats, hypophysectomized at 12 months of age, was closest to that in 3-month-old intact rats and was not significantly different from that in liver nuclei of 0.75-9-month-old intact rats.

Adenosine Triphosphate↗
PubMed1979

Effect of hypophysectomy on liver nuclear ribonucleic acid synthesis in aging rats.

Changes in RNA synthesis in liver nuclei were observed at different ages and after hypophysectomy and hormone replacement in female Sprague-Dawley rats. As determined by the incorporation of [3H]UMP into an acid-insoluble product, RNA synthesis decreased by about 75% in intact rats from 6 months to 24 months of age. This decline with age was not observed in liver nuclei from 24-month-old rats that had been hypophysectomized at 12 months and maintained on a minimal hormone-replacement therapy. Thyroid hormones and somatotropin (growth hormone) had an additive effect on RNA synthesis in liver nuclei from these hypophysectomized rats. The same hormones had no significant effect on intact, age-matched rats. With advancing age, nuclei of intact rats had an increase in the pool of free RNA polymerase and an apparent decrease in the enzyme activity bound to nuclear chromatin. There was no change in total enzyme with age. In hypophysectomized, hormone-treated rats, free RNA polymerase activity decreased and chromatin-bound activity increased. There was no difference in total nuclear RNA polymerase activity between operated or intact rats. However, the ratio of the bound to the free activity was different. These results suggest that the ability of RNA polymerase to bind to chromatin may be involved in the age-related decrease in liver nuclear RNA synthesis of intact rats.

Aging↗
PubMed1979

Age-related changes in immune function of rats and the effect of long-term hypophysectomy.

The effect of age on the ability of rats to raise antibodies to sheep erythrocytes and on the number of IgM plaque-forming cells in the spleen was investigated. An age-related decline in both parameters was observed. Additionally, the possibility that long-term hypophysectomy coupled with minimal replacement therapy might result in a delay and/or reversal of the age-related decline in immune function was studied. It was observed that long-term hypophysectomized rats responded better to immunization with sheep erythrocytes than did their age-matched unoperated littermates. The possible relationship of this to aging is discussed.

Aging↗
PubMed1978

Vascular relaxation, aging and thyroid hormones.

Previous work indicates vascular can be studied in vitro and that there is a marked age-associated decrease in the ability of rat aortic strips to relax in response to beta-adrenergic agonists. The present studies were aimed at better understanding the role of thyroid hormones in vascular relaxation and aging. Removal of the thyroid gland from young rats resulted in a decrease in the ability of isoproterenol to relax the aorta. Relaxation caused by nitroglycerin, a non-specific relaxant, was not impaired by thyroidectomy. In 22-month-old rats, isoproterenol caused no relaxation unless exogenous thyroid hormones were administered. Hypophysectomy seven months prior to testing improved the ability of thyroid hormones to restore isoproterenol relaxation of the aorta. The loss of relaxation with age could be due in part to a pituitary mediated loss of responsiveness of aortic tissue to thyroid hormones. The data provide new evidence for the importance of thyroid hormones in beta-adrenergic receptor mediated vascular relaxation and demonstrate that the loss of aortic relaxation with aging can be reversed.

Aging↗
PubMed1978

Interactions between age and the neuroendocrine and immune systems.

Three conclusions are suggested by some of the recent work on aging, immunology and the neuroendocrine system. 1) There appears to be sufficient data to implicate the neuroendocrine system in both the maturation and the senescence of at least some components of the immune system. 2) The thymus by its presence or its absence appears to influence certain functions of the pituitary; thus, there appears to be a possible reciprocal relationship between the pituitary and the thymus. 3) Changes in the levels of pituitary hormones or hormones that are controlled by the pituitary can restore in older rats and mice certain functions that are generally considered as part of the immune surveillance and defense system. Consequently, it can be hoped that further studies of neuroendocrine-immune relationships might lead to an understanding of some of the causes for the decline in immune competence with age in mammals.

Adrenocorticotropic Hormone↗
PubMed1975

A time to die.

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Aging↗
PubMed1975

Pituitary inhibitor of thyroxine.

A description is given of a new pituitary function. It is suggested that the new function acts to decrease gradually the responsiveness of the peripheral tissues to thyroid hormones throughout life. It is suggested that the postulated relative hypothyroidism of older animals might contribute to their loss of viability.

Aging↗
PubMed1974

Role of the pituitary and thyroid glands in the decline of minimal O2 consumption with age.

Resting O2 consumption rate (BMR) or minimal O2 consumption rate (MOC) declines with age. Data are presented that suggest that a newly described function of the pituitary may be responsible for a considerable part of the total 75% decline in the MOC with age. The new function appears to decrease the responsiveness of peripheral tissues to thyroid hormones. Response curves to injected thyroxine indicated that immature rats were three times more responsive to thyroxine than adult rats. All the major endocrine ablations were performed in this and earlier work, and only pituitary ablation (a) restored in adults part of the responsiveness to thyroxine found in immature rats and (b) arrested the normal age-associated decrease in responsiveness to thyroxine in immature rats. Bovine pituitary extracts were found that decreased the responsiveness of immature rats to thyroxine. Experiments with the new pituitary function suggested a possible endocrine mechanism to explain why partial starvation doubled the lifespan for rats only when started before puberty.

Aging↗