Neuroendocrine features in extreme longevity

In order to evaluate the effects of some neuro-endocrine changes during aging we have studied adrenal, thyroid and pineal secretion in young, healthy old and centenarians. The number of subjects in each hormone group varied. The following parameters were evaluated: serum levels of cortisol, dehydroepiandrosterone-sulfate (DHEAS), free triiodothyronine (FT3), thyroxine (FT4), reverse triiodothyronine (rT3) and thyroid-stimulating hormone (TSH). Urinary 6-hydroxymelatonin sulfate (aMT6s) and free cortisol were measured twice daily. Centenarians exhibited significantly lower TSH levels together with slightly higher rT3 levels than old controls. These changes could be due to reduced 50-deiodinase activity occurring also in absence of substantial changes of the nutritional pattern. Morning serum cortisol levels were found to be similar in the 3 age groups, whereas the decline of serum DHEAS levels was well evident also after the ninth decade of life. The cortisol/DHEAS molar ratio, which usually increases with age and considered to be an expression of a neurotoxic pattern of the steroidal milieu in the central nervous system, did not shown any further increase in centenarians. The urinary free cortisol and aMT6s excretion declined with age; however only in centenarians and in young controls aMT6s excretion was significantly higher at night than during the day. These findings suggest that the circadian rhythm of melatonin secretion is maintained in centenarians and, based on the limitations of this study, could be considered one factor in successful aging. 2007 Elsevier Inc. All rights reserved. Keywords: Centenarians; Melatonin; TSH; Thyroid hormones; Cortisol; DHEA-S 1. Introduction Physiological aging involves both the central nervous system [CNS] and the endocrine system. Both of these systems are essential for the maintenance of the homeostasis. Age-related changes in the CNS include progressive neuronal loss with compensatory gliosis, particularly marked in the hypothalamus, hippocampus and limbic system and imbalance among neurotransmitters and other neuro-modulatory molecules. These features may play a role in the patho-physiology