Lucio Piantanelli

Thymus-dependent recersibility of physiological and isoproterenol evoked age-related parameters in athymic (nude) and old normal mice

In order to assess the relationship between the thymus and aging processes, a linear age-dependent parameter in mice such as the response of the submandibular gland to an injection with isoproterenol has been evaluated in athymic (nude) and thymectomized Balb/c mice. The IPR-induced DNA synthesis is reduced in both experimental groups when compared to untreated normal littermates and is recovered by grafting a neonatal thymus. Moreover, the impairment of IPR response in old animals is recovered to young levels by grafting one neonatal thymus one month before test. Neonatal thymus grafts in old recipients are also able to correct their abnormal serum levels of triiodothyronine and insulin. The influence of neonatal thymus on such non-immunological and age-related parameters suggests that this gland can control aging processes, probably through its implication with the endocrine system.

Thymic regulation of brain cortex beta-adrenoceptors during development and aging

The influence of the thymus on beta-adrenoceptors has been studied in the brain cortex of mice during developing and aging. Affinity of beta-adrenoceptors shows no statistically significant changes in the various animal models investigated. Receptor density shows a fall in both athymic nude mice and in old normal mice. Receptor density, in particular, decreases progressively with advancing age. It has been demonstrated that thymus exerts a regulatory role in both development and aging, as a neonatal thymic graft is capable of reversing the receptor impairments found in young athymic nude mice and in old normal mice.

Beta-adrenoceptor changes in submandibular glands of old mice

The hypothesis that modifications in beta-adrenergic receptors may be responsible for age-dependent change previously observed in vivo, has been investigated. Beta-adrenoceptor characteristics of submandibular glands of mice were studied by using the beta-adrenergic antagonist (-)-[3H]dihydroalprenolol. Data from such studies indicated the presence of two functional populations of binding sites in membrane preparations from young animals, displaying high and low affinity, respectively. Experiments performed on old mice membrane preparations revealed a 50% decrease in the high-affinity population receptor number when compared to the preparations from young animals. However, the affinity did not change significantly with advancing age. With regard to the low-affinity population, no statistically significant changes were observed. From these data it can be reasonably assumed that beta-adrenoceptor alteration during ageing may play a major role in the age-dependent impairment of beta-adrenergic responses in vivo.

Ageing and thymus-induced differential regulation of β1 and β2 adrenoceptors of mouse brain cortex

Abstract Two questions have been addressed by the present paper, that is, the differential influence of age on β 1 and β 2 receptors and the thymus-induced recovery of such changes. Age-related changes in receptor density and affinity have been assayed in brain cortex of Balb/c-nu mice of different ages. Results have shown a progressive decrease of β 1 receptor density with advancing age, while no statistically significant changes were observed in β 2 receptor density. Receptor affinity did not show any changes among the various groups examined. The influence of the thymus on receptor characteristics has been studied comparing young, old and thymus-grafted old mice. Total receptor density, which is decreased in old animals, can be up-regulated by thymus graft in old recipients. Interestingly, such a corrective effect is exerted only on the β 1 population, the β 2 receptor not being significantly affected. Thymic graft, therefore, acts just on the population which is found altered during ageing.

Insulin receptors in the brain cortex of aging mice

The aim of the present study was to analyze whether aging also affects central insulin receptors in brain cortex as it does in whole brain of BALB/c-nu mice. Results showed statistically significant decrease of number and increase of affinity of insulin high affinity binding sites in old animals. As a consequence, central insulin actions, among which neuromodulation of monoaminergic system, can result altered during aging.

Age-dependence of isoproterenol-induced DNA synthesis in submandibular glands of BALB/c mice.

The age-dependency of isoproterenol (IPR) induced DNA synthesis was investigated in different organs of Balb/c mice. Although modifications of the physiological rate of DNA synthesis after IPR injection occurred also in liver and spleen, a quasi-linear decrease of the peak of IPR response with advancing age was observed only in submandibular glands. Such a decrease was observed when animals were injected with 10(-4) g IPR per g body weight, lower doses being unable to discriminate between young and old mice. In spite of some differences between mice and rats, the early appearance and linearity of the age-dependency remain common features of IPR response.

Neurochemical parameters of the main neurotransmission systems in aging mice

The present work was designed to study the effect of aging on some parameters of the glutamatergic, aminergic and cholinergic neurotransmission, in the main brain areas of mice of the long-surviving BALB/c-nu strain. We have assayed: (1) the density of three ionotropic receptors for excitatory aminoacids (EAA) which selectively bind kainic acid (KA), N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA); (2) the content of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) and the levels of the DA metabolite dihydrophenylacetic acid (DOPAC) and the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA); (3) the level of the choline acetyltransferase (ChAT), the enzyme catalyzing the synthesis of acetylcholine. The parameters were measured in animals at the age of 6, 12, 18 and 24 months; the brain zones under test were the frontal cortex (FC), the corpus striatum (STR), the hippocampus (HIP), the medio-dorsal cortex (DC) and the cerebellum (CER). Significant age-related variations for the density of KA-type and NMDA-type receptors were found in STR and a decrease of the NMDA parameter was found in DC. Neither the monoamine and metabolite contents nor the ChAT levels showed any significant variation in all the tested areas. These findings suggest that an unbalance among different neurotransmission activities could take place with normal aging in rodents: it could be involved in the onset of the motor deficit which occurs in the elderly of these and other mammals.

Food restriction in female Wistar rats. I. Survival characteristics, membrane microviscosity and proliferative response in lymphocytes.

The effect of food restriction on the survival characteristics, membrane microviscosity and proliferative response in lymphocytes of female Wistar undernourished rats has been evaluated. Diet restriction was applied starting from the age of 3.5 months by feeding the animals on an every-other-day schedule (EOD). Diet restricted animals showed an increase of both mean, median and maximal life span as compared to the rats fed ad libitum (AL). Analyzing the survival curves by a parametric model, it emerged that undernutrition increased the individual resistance to environmental insults. In particular, it could be speculated that the positive influence was more pronounced in individuals with the lowest physiological capacities. The membrane microviscosity of lymphocytes was lower in EOD animals as compared to the AL ones even if one assumes a decrease in body temperature of 1-2 degrees C in EOD groups. The improvement of membrane microviscosity due to diet restriction may in part explain the improvement of proliferative response of lymphocytes from EOD groups.

Age-dependent decrease of beta-adrenoceptor density in the submandibular glands of mice and its modulation by the thymus

Beta-adrenergic receptors were characterized in submandibular glands of ageing mice and old mice grafted with a neonatal thymus. No statistically significant changes of receptor affinity were found in the animal models investigated. On the contrary, receptor density showed a progressive decrease with advancing age. The age-related decrease has been found partially corrected in thymus-grafted old animals, which show a statistically significant recovery of receptor density when compared to their untreated littermates. Receptor modulation can be responsible for the age-related impairment and the thymus-dependent correction of beta-adrenergic responsiveness of submandibular glands previously observed in vivo. Hormonal balance and thyroid hormones, in particular, are suggested as being involved in the age- and thymus-dependent regulation of receptor density. In the accompanying Appendix, we describe the mathematical method used to calculate both specific and nonspecific binding from total binding data.

Relationship between plasminogen activator inhibitor type-1 plasma levels and the lipoprotein(a) concentrations in non-insulin-dependent diabetes mellitus.

The first part of the paper deals with the relationship between two inhibiting factors of the complex enzyme cascade regulating fibrinolysis, namely plasminogen activator inhibitor type-1 (PAI-1) and lipoprotein(a) (Lp(a)). Blood concentrations of Lp(a), PAI-1 antigen (PAI-1 AG) and activity (PAI-1 AT), and the main parameters of lipo- and glyco-metabolic balance were studied in 80 type II diabetic patients. Roughly hyperbolic patterns have been found between PAI-1 and Lp(a). Negative statistically significant linear correlation can be elicited when Log PAI-1 AG and Log PAI-1 AT values are plotted versus Lp(a) values, the first one being particularly tight. These findings suggest a nearly on/off control of the two parameters, limiting the risk of hypofibrinolysis. The second part of the paper was aimed at verifying this hypothesis. A group of 30 diabetic patients were treated for 3 months with metformin, an antidiabetic biguanide compound which has been reported to reduce PAI-1 levels both in diabetic and in non-diabetic patients. Metformin significantly reduced PAI-1 AG and PAI-1 AT but did not influence plasma Lp(a) levels. A clear linear correlation between the basal Lp(a) values and the changes in PAI-1 AG levels was found. An even tighter correlation was elicited between the decrease in PAI-1, and PAI-1 pretreatment values.