Student Theses and Dissertations

Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)


Although much is known about manifestations of ageing in mammals, the fundamental cause of ageing has remained obscure. Review of a widely scattered literature has demonstrated a histotypic selectivity in the effect of ageing on cell activitjes. Several recent examples have shown that certain age changes in cell activities can be reversed by transplantation to a young host. Thus, ageing does not appear to diminish the potential for genomic function. The selective and reversible age changes in cell activities are interpreted to be the result of a differential change in gene activity, which appears to be mediated at the supra-cellular level by humoral factors. Evidence for age changes in regulation at the supra-cellular, physiological level was revealed in an experimental study of the effect of ageing on the response of C57Bl/6J male mice to cold stress. Marked changes in the regulation of body processes were revealed by a study of three parameters. (1) The induction of liver tyrosine aminotransferase (TAT), an enzyme shown to be rapidly induced in a gene-mediated reaction during cold stress in young mice (4-16 months old) was delayed up to 2 hours in senescent mice (26-28 months old); the rate of increase after the delay was similar to that in young mice. Direct challenge of liver cells with injections of insulin and corticosterone, hormones which induce TAT in the perfused, isolated liver, resulted in an identical time course of TAT induction. Hence, the delayed TAT induction during cold stress in senescent mice is probably not the result of a primary age change in the liver; an age change in the regulation of extra-hepatic. which mediate the induction of TAT is implied. (2) In contrast to the regulation of liver cell activities, no age changes were found in the time course of adrenal corticosterone secretion during cold stress. (3) Finally, senescent mice were shown to have a striking inability to maintain body temperature during short exposure to cold. This defect in thermal regulation is the likely capse of the decreased ability of ageing mice to survive cold stress. In conclusion, no evidence for a loss of the potential for cell function was found in senescent mice. However, selective age changes in regulation, at a supra-cellular, physiological level were revealed during cold stress.


A thesis submitted to the Faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy

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