AN ALTERED RESPONSE IN THE INDUCTION OF CELL-MEMBRANE (NA+K)ATPASE BY THYROID-HORMONE IS CHARACTERISTIC OF SENESCENCE IN CULTURED HUMAN-FIBROBLASTS

There have been numerous investigations of thyroid function during senescence in humans. However, very little information is available on thyroid hormone action at the cell level during senescence. Therefore, we have investigated thyroid hormone induction of cell membrane (Na + K)ATPase during human senescence using three experimental fibroblast cell culture systems: cells from premature aging syndrome, progeria; aging in vitro; and early passage cells from aged patients. In all cases senesence is associated with a dramatic alteration from the normal dose-dependent thyroid hormone induction of (Na + K)ATPase. Senescent cells depleted of thyroid hormones demonstrated an elevated activity of (Na + K)ATPase, while non-senescing cells exhibit the characteristic basal enzyme activities in the hypothyroid state. These results indicate that human senescence is associated with extreme alterations in thyroid hormone regulation of (Na + K)ATPase; and may suggest a more general change in thyroid hormone action at senescence. These changes may be associated with important alterations in cell metabolism and intracellular ionic environment during senescence.