G. Carnazzo

Pathophysiology of the immune system in elderly subjects with or without diabetes and variations after recombinant interleukin-2

This study reports two groups of elderly diabetic patients and normal subjects, with or without hypercholesterolemia and hypertriglyceridemia, who presented a decrease of the T lymphocyte-mediated function, proliferative capacity, phagocytosis, cytotoxicity and surface markers. This fall was more evident in hypercholesterolemic and hypertriglyceridemic subjects. The humoral responses and other parameters studied did not reveal significant variations. The authors also observed that recombinant interleukin-2 (rIL-2) stimulation determined a satisfactory response in healthy and diabetic subjects, while it did not normalize values in patients with altered lipid balance.

Atherosclerosis and pancreatic damage

The appearance of diabetes in advanced age may be considered as a part of the involutive processes of aging, and as such, it might have a pathogenesis completely different from that of type 2 diabetes of medium age. As a matter of fact, it has been observed that the pancreas undergoes numerous structural and functional alterations with advancing age, both in exocrine and endocrine parts. The present studies have been performed to reveal the quantity and quality of the pancreatic lesions, which may be attributed to atherosclerosis. We have already studied elderly subjects, therefore, we were now looking for further supports in a population of middle age people, died in complications of malignant hypertension. We investigated the pancreas, kidney and heart of 36 subjects (20 males and 16 females) with mean age of 48.6+/-8.9 years. Of this group, eight subjects (22.2%) became diabetic after the appearance of malignant hypertension. Arteriolar atherosclerosis damage (hyalinosis, thickening and stenosis) of the pancreatic arterioles were found in 92.8% of the non-diabetic, and in 87.5% of the diabetic subjects. Lesions of the pancreatic islets were observed in 32% of the non-diabetics, and in 50% of the diabetic subjects. The pancreas is an organ, which tends particularly to develop atherosclerotic damage. The vascular lesion of atherosclerotic origin, independently from the mechanism of its appearance, causes first only a decrease of the blood flux and hypoxia in the pancreatic islets with a consecutive functional decline of the beta-cells. This is then followed by structural modifications of the islets accompanied by the appearance of hyalinosis, loss of beta-cells, and a further decrease of insulin production.

Prevalence of diabetes mellitus in a sample of the elderly population of the city of Catania.

The prevalence of diabetes mellitus is increasing world-wide, even if it varies markedly in the geographical areas and populations investigated. This study is part of the Progetto Finalizzato Invecchiamento (Aging Project) of the Italian NCR (National Research Council) and is aimed at investigating the prevalence of diabetes and selected clinical characteristics in a study sample aged between 65 and 84 years of age resident in Catania (Italy). The prevalence rate for type II diabetes was 22.8% and it is certainly among the highest values recorded to date in other areas of Italy and abroad. We distinguished between two forms of diabetes in subjects >70 years of age: aged diabetes with onset in middle age (AD); and diabetes of senescence with onset after 70 years of age (DS). Prevalence rate was 18% for AD and 4.8% for DS, respectively. The age-specific rates of AD and DS show the progressive lower prevalence rates of the former and the higher rates of the latter. We assume that DS is mainly caused by atherosclerotic processes and represents the typical form of diabetes in the elderly.

Comparison between serum interleukin-2 concentrations in healthy adult and elderly subjects

The serum interleukin-2 (IL-2) concentrations were evaluated in healthy elderly patients, enrolled under the SENIEUR protocol, and healthy adult controls. The aim of the study was to ascertain whether the reduced immune response, described during aging, is linked to deficient production of IL-2 or to its receptorial deficit, or if the reduced serum IL-2 concentrations observed during aging can be used as a biological immunodeficiency marker. The results obtained did not show any significant differences between the study groups, even if mean values were slightly decreased in the elderly group, as compared to the adult one. This finding does not justify the age-dependent deficiency of the immune response, i.e., to explain this condition, one needs another pathogenetic hypothesis. It is suggested that one such hypothesis could be the alteration of IL-2 receptors which undergo major cleavage and minor re-expression in the elderly, causing this way some receptorial changes with consequent reduction of T-helper activation.

Senile diabetes and bone mineral density

Bone mineral density was determined in a series of 67 elderly diabetics (38 males and 29 females) and 40 non-diabetic elderly subjects (20 males and 20 females) at the third medial and tenth ultradistal of the non-dominating radius using an X-ray densitometer (DEXA). Bone metabolism markers (Ct, PTH, HOP, UCA, AP, Vit-25-OH-D, BGP) were also measured. Our results indicate that there is no significant difference in values of BMD and the bone metabolism markers studied between diabetic and non-diabetic elderly subjects. We believe that senile diabetes is not a risk factor of onset and maintenance of senile osteoporosis.

Expression of cell cycle-dependent genes and proliferative state of lymphocytes in aging

The authors analyzed the expression of some genes involved in the control of T lymphocyte proliferation in a group of healthy elderly subjects. They focused their attention on genes involved in the G(0)/G(1) transition (TK, PCNA, H3, IL2-R) and showed decreased expression in the TK, H3 and IL2-R genes. Using flow cytofluorimetry, delayed transition from the G(0)/G(1) to the S stage was observed.

Expression of ornithine decarboxylase gene in elderly human monocytes

The proliferative capacity of the immune system is impaired in elderly subjects and the expression of various genes involved in cell cycle progression is reduced in PHA stimulated lymphocytes during the aging process. Macrophages play a fundamental role in the immune system response. It has recently been demonstrated that the process of macrophage activation is accompanied by a rapid, transient rise of ornithine decarboxylase (ODC) mRNA levels. In fact, the ODC gene seems to be involved in macrophage activation and differentiation. The authors demonstrated that the steady-state levels of ODC mRNA and the correlated superoxide anion production are lower in the monocytes of elderly subjects with respect to those in young subjects used as control. These results confirmed the impaired immune function of the elderly.