N.D. Goncharova, B.A. Lapin

Endocrine system takes part in the organization of the processes and functions that are affected by aging in the first turn: complex forms of behavior, nonspecific adaptation to stress factors of environment, reproduction, homeostasis, immune states, higher nervous activity, etc. This is why it may be suggested that age endocrine disturbanses are important factors of the processes of physiological aging and age pathology. On the other hand relative "rejuvenation" of some age related diseases in contemporary stressful time point to great significans of endocrine disorders in premature aging pathogenesis.

Purpose: Studying of the changes in the pineal gland, hypothalamic-pituitary-adrenal (HPA) axis, and hypothalamic-pituitary-testicular (HPT) axis function during aging; evaluation of their role in physiological aging and some age-related diseases.

Material and methods: Forty male baboons (Papio hamadryas) and 70 female rhesus monkeys (Macaca mulatta) were observed for function of HPA, HPT and the pineal gland in different age periods (from 6 to 27 years old) at basal conditions and during specific stimulation or inhibition. Plasma hormone levels were determined by radioimmunoassay and immunoenzyme methods.

Results: It has been established that the level of adrenal androgens (DHEA, DHEAS) progressively decreases during aging which results in sharp increase of cortisol/DHEA+DHEAS ratio. This fact may have an important physiological meaning because these corticosteroid fractions are antagonists in their influence on some physiological systems, e.g. immune and nervous. The HPA system sensitivity to corticosteroid feedback inhibition decreases. Restoration of the initial level of cortisol after activation of adrenals by corticotrophin-releasing hormone (CRH) or corticotrophin (ACTH) of short action slows down which results in prolonged hypercortisolemia in old age. In contrast to cortisol, old animals exhibited a lower DHEAS response to CRH and ACTH. In the same time reactiveness of the pituitary to CRH administration was accelerated in aging monkeys in comparison with young monkeys. In male baboons concentration of 5alfa-dihydrotestosterone (DiHT) significantly decreased in old animals that led to increase of the ratio estradiol to testosterone plus DiHT. Slowing down of restoration of the pituitary-testicular axis function was noted after its activation by LHRH administration and also some refractoriness to inhibitory effect of LHRH agonists was detected. Activity of the pineal gland decreased in aging. Some age-related changes in circadian rhythm of hormone secretion were detected, in particular, amplitude of circadian rhythm of cortisol and melatonin decreased.

Conclusions: Hormonal function of the HPA, HPT systems and the pineal gland undergo complex age-related changes. Age endocrine changes perhaps play a pathophysiologic role in age function disorders of hormonocompetent tissues and organs and age pathology. Timely correction of such endocrine disturbances perhaps could be important for age pathology treatment and also in prevention for premature and/or accelerated aging. Main age-related endocrine dysfunctions revealed in non-human primates are similar to those detected in humans.

Keywords (Optional): 
pineal gland
SENS Research Themes: 
Ending Aging: