The endocrine system is as affected by aging as are other systems. The effect of aging on the hypothalamuspituitary- thyroid function is still controversial. Human aging was reported as associated with a decrease in thyrotropin (TSH) secretion, but increased TSH levels in relatively healthy elders are also reported. The main point discussed is whether this increase in the immunoreactive TSH of aged subjects, and related changes in thyroid function, are “physiologic” consequences of aging on the hypothalamus-pituitary-thyroid axis or are induced by non-thyroid illnesses and/or drug use, frequent in the elderly. There are strong evidences of decreased hypothalamus-pituitary-thyroid axis activity as well as decreased thyroxine metabolism (5-deiodination) in humans, and other mammals. For now, we must consider that the hypothalamus-pituitary-thyroid axis is affected at all three levels by normal aging, and the mild state of “total” hypothyroidism during aging is completed by a reduced response of target cells/tissues to thyroid hormones. Despite the decreased response of the old rat thyroid to TSH there is no decrease in the glands mass. Ras proteins are involved in the transduction of growth factor signals by surface receptors, in thyroid as well as in other tissues, and are key components of downstream signaling through several pathways. Ras activation of Raf, and of extracellular-signal-regulated kinases (ERK) is an important signaling pathway for many Ras effects. Very little is known about the modulation of Ras expression in the aging thyroid. We detected an increase in Ras expression in thyroids of old rats, but the signal transduction by pERK was decreased, suggesting that another RAS-signaling pathway could be activated and responsible for the maintenance of the thyroid volume.