Biologia Futura: does the aging process contribute to the relativity of time?

In his Theory of relativity, Einstein determined that the time is relative to the reference frame of the observer. Under specific conditions, there is a difference in the elapsed time between two clocks, known as time dilation. A similar relativistic effect could be attributed to the brain operating at different frequencies, e.g., while it is slow and during the thought process. Time flow and the aging process are causally linked. Herein, we introduce physical relativity into the mind/thought context and elaborate changed perception of the time flow (the impression of the time acceleration) with aging. The phenomenology of time is observed in the context of physical and biological clock, as well as by introducing the category of 'mind time.' Mental processing impairment is crucial for the "aging-caused relativity of time," while adjusting of its' perception seems to be a matter of body/mind rest, mental hygiene and physical activity of the aging subject. We also provide a brief overview of the perception of time flow in some disease states that coincide with aging. Our main idea has a perspective for future development in the interdisciplinary synergy of philosophy, physical-mathematical elaboration, experimental biology and clinical investigations.

Soy isoflavone effects on the adrenal glands of orchidectomized adult male rats: a comprehensive histological and hormonal study.

Genistein (G) and related soy phytoestrogens have been studied for potential usefulness in different chronic diseases, and may ameliorate signs of aging. They have a profound influence on the hypothalamo-pituitary-adrenal (HPA) axis. The present study utilized the rat model of mild andropause to thoroughly evaluate the effects of G and soy extract on the adrenal gland and related blood hormones. Adult male rats were orchidectomized (Orx) or sham operated (SO). Orx rats received daily subcutaneous injections for 3 weeks of solvent, or G (Orx+G, 30 mg/kg), or commercial soy extract (Orx+Soy, 30 mg/kg). Adrenal glands and blood were harvested at the end of the treatment for hormone analyses, histology and design-based stereology. Compared to SO rats Orx evoked significant (P<0.05) changes including: the replicating cell number in the 3 adrenocortical zones; vascularity and cortical volume and blood levels of adrenocorticotropic hormone (ACTH), aldosterone and dehydroepiandrosterone (DHEA). When comparing Orx vs. Orx+G groups the following significant (P<0.05) changes were observed: a further increase in number of replicating cells in zonas glomerulosa and reticularis, vasculature network presence, cortical and zona reticularis volumes, ACTH and corticosterone concentrations, and lower DHEA levels. Comparing Orx vs. Orx+Soy resulted in elevated (P<0.05) ACTH and corticosterone levels. Structural integrity of the adrenal gland was unchanged vs. SO rats. Overall, G and soy extract treatments resulted in proliferative activity and/or vasculature support in the adrenal cortex. The data and current literature support the impression of a beneficial effect of soy components on the homeostatic response to stress.

Testosterone supplementation, glucocorticoid milieu and bone homeostasis in the ageing male.

Male ageing is entwined with a continuous fall in free testosterone levels, which contributes to the pathogenesis of bone loss. Glucocorticoid excess, either dependent on the ageing process or iatrogenically induced, was found to additionally impair the bone structure and metabolism. Cautious testosterone supplementation in this respect may positively affect the glucocorticoid milieu and bone homeostasis, while testosterone-induced changes in the glucocorticoid output could serve as a determinant of bone-related therapeutic outcome. Namely, bone mineral content/density, the parameters of trabecular bone structure as well as bone strength are enhanced, serum calcitonin levels tend to increase, while serum osteocalcin, serum parathyroid hormone and urinary calcium decrease, all upon testosterone administration to the ageing male. In parallel, testosterone application decreases glucocorticoid secretion in the animal models of male ageing, while clinical data in this field are still inconsistent. Importantly, a physiological link exists between testosterone-induced changes in glucocorticoid levels and the tendency of bone status improvement in the ageing male. We believe that the assessment of circulating adrenocorticotropic hormone concentrations together with glucocorticoid levels, reflecting the hypothalamic-pituitary-adrenal axis feedback loop operativeness during testosterone supplementation, represents a well-balanced bone-related therapeutic update.

Histological parameters of the adrenal cortex after testosterone application in a rat model of the andropause.

Histological analysis of the adrenal cortex, after testosterone application in a rat model of the andropause, was the main subject of the present study. Middle-aged Wistar rats were divided into sham-operated (SO; n=8), orchidectomized (Orx; n=8) and testosterone treated orchidectomized (Orx+T; n=8) groups. Testosterone propionate (5 mg/kg b.w. /day) was administered for three weeks, while SO and Orx groups received the vehicle alone. Histological objectives were achieved using stereology, histochemistry and steroid receptor immunostaining. The concentrations of testosterone, aldosterone, corticosterone and DHEA were determined by immunoassays. Expectedly, increased (p<0.05) serum concentration of testosterone was observed in Orx+T group. The volume of ZG cells and nuclei increased in Orx+T animals by 50% and 25% (p<0.05) respectively, but the serum concentrations of aldosterone decreased (p<0.05) by 60%, all compared to the same parameters in Orx group. The immunostaining for androgen receptors (ARs) suggested their cytoplasmic localization in ZG cells of Orx+T rats. Volume of the ZF cell nuclei in Orx+T group decreased (p<0.05) by 17%, which was followed by the significant (p<0.05) fall in corticosterone production and secretion, all in comparison with Orx animals. Also, nuclear immunolocalization of ARs of high optical density was observed through the ZF of Orx+T group. In Orx+T rats volume of ZR cells and nuclei, and circulating DHEA concentration increased (p<0.05) by 68%, 22% and about 6.6 times respectively, compared to Orx animals. Besides the extra-receptor actions in adrenal cortex, testosterone supposedly affects some steroidogenesis-related gene expression, as indicated by centripetal rise in the number of nuclear ARs.

Morpho-functional characteristics of rat fetal thyroid gland are affected by prenatal dexamethasone exposure.

Thyroid hormones (TH) and glucocorticoids strongly contribute to the maturation of fetal tissues in the preparation for extrauterine life. Influence of maternal dexamethasone (Dx) administration on thyroid glands morpho-functional characteristics of near term rat fetuses was investigated applying unbiased stereology. On the 16th day of pregnancy dams received 1.0mg/Dx/kg/b.w., followed by 0.5mg/Dx/kg/b.w. on the 17th and 18th days of gestation. The control females received the same volume of saline. The volume of fetal thyroid was estimated using Cavalieri's principle; the physical/fractionator design was applied for the determination of absolute number of follicular cells in mitosis and immunohistochemically labeled C cells; C cell volume was measured using the planar rotator. The functional activity of thyroid tissue was provided from thyroglobulin (Tg) and thyroperoxidase (TPO) immunohistochemical staining. Applying these design-based modern stereological methods it was shown that Dx treatment of gravid females led to a significant decrease of fetal thyroid gland volume in 19- and 21-day-old fetuses, due to decreased proliferation of follicular cells. The Tg and TPO immunohistochemistry demonstrated that intensive TH production starts and continues during the examined period in control and Dx-exposed fetuses. Under the influence of Dx the absolute number of C cells was lower in both groups of near term fetuses, although unchanged relation between the two populations of endocrine cells, follicular and C cells suggesting that structural relationships within the gland are preserved. In conclusion maternal glucocorticoid administration at the thyroid gland level exerts growth-inhibitory and maturational promoting effects in near term rat fetuses.

Long-term effects of somatostatin 14 on the pituitary-ovarian axis in rats.

The long-term effects of somatostatin 14 (SST-14) on the pituitary-ovarian axis were examined. Female Wistar rats received 20 µg/100g b.w. doses subcutaneously twice daily for 5 consecutive days in the infantile (from 11th to 15th day) or peripubertal (from 33rd to 37th day) period of life. Females treated as infants were killed in the peripubertal (38th day) or adult period of life (80th day), and those treated during peripuberty as adults (80th day). Pituitary follicle-stimulating (FSH), luteinizing (LH) and somatotropic (GH) cells, and ovaries were analyzed by stereology and morphometry. Serum FSH and LH concentrations were determined by RIA. FSH and LH cell volumes were significantly decreased in pituitaries of peripubertal females treated with SST-14 as infants, and in adult females treated during peripuberty. GH cell volume was decreased in all treated rats. In the ovaries, enlargement of the non-growing pool of follicles was detected in adult females treated during peripuberty. SST-14 applied to infant rats did not lead to changes in initial follicular recruitment, but it disturbed follicle growth and development at later stages. It can be concluded that SST-14 exerted long-term inhibitory effects on the pituitary-ovarian axis and GH cells in rats.

Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study.

Ghrelin, a growth hormone secretagogue that exerts an important role in appetite and weight regulation, participates in the activation of the hypothalamo-pituitary-adrenal (HPA) axis. Male Wistar rats (5/group) received daily for 5 days, via an ICV (intracerebroventricular) cannula, 5 microl phosphate buffered saline with or without 1 microg of rat ghrelin. Two hours after the last injection, blood and adrenal glands were collected from decapitated rats for blood hormone analyses and histologic and morphometric processing. Ghrelin treatment resulted in increased (p<0.05) body weight (13%), absolute whole adrenal gland weight (18%) and whole adrenal gland volume (20%). The absolute volumes of the entire adrenal cortex, ZG, ZF, and ZR also increased (p<0.05) after ghrelin by 20%, 21%, 21% and 11%, respectively. Ghrelin-treated rats had elevated (p<0.05) blood concentrations of ACTH, aldosterone and corticosterone (68%, 32% and 67%, respectively). The data clearly provide both morphological and hormonal status that ghrelin acts centrally to exert a global stimulatory effect on the adrenal cortex. Clarifying of the ghrelin precise role in the multiple networks affecting the stress hormone release, besides its well known energy and metabolic unbalance effects, remains a very important research goal.

Morphofunctional characteristics of ACTH cells in middle-aged male rats after treatment with genistein.

The soybean phytoestrogen, genistein, is increasingly consumed as an alternative therapeutic for age-related diseases. The aim of this study was to examine the morphofunctional characteristics of adrenocorticotrophic (ACTH) cells and blood concentrations of ACTH in sham-operated, orchidectomized and genistein-treated orchidectomized, 16-month-old Wistar male rats. Genistein (10 mg/kg/day) was administered subcutaneously for three weeks, while the control groups received the vehicle alone. Orchidectomy and genistein treatment decreased the volume density of ACTH cells and reduced (p < 0.05) circulating ACTH concentrations in comparison with control groups. In conclusion, genistein modulated the morphofunctional features of ACTH cells and decreased blood ACTH levels.