Vittorio Nicita-Mauro

Smoking, aging and the centenarians.

The smoke of cigarettes represents an important accelerator of the aging process, both directly through complex mechanisms mediated prevalently by excessive formation of free radicals, and indirectly by favoring the appearance of various pathologies in which smoke is a recognized risk factor. This means that smoke compromises not only life expectancy, but also the quality of the life, favoring the occurrence of non-autosufficiency. Smoking is an important risk factor for many diseases, such as cancer, cardiovascular and respiratory diseases. These are also the main causes of death in the industrialized Countries, where the habit of smoking is also largely diffused. Non-smokers have a much higher life expectancy than smokers, and the suspension of smoking is accompanied, even in the elderly, by an increase in the survival time due to the reduction of smoke-induced biological damage. Therefore, cigarette smoking is opposing the longevity, particularly the extreme one, as it is confirmed by the observations obtained on centenarians. Among them, smoking is extremely rare, and even when it occurs among them, it is correlated almost exclusively to bad health conditions and non-autosufficiency, indicating that it compromises health status and the quality of life even in extremely long living subjects. Considering the demonstrated beneficial effects of suspension of smoking, all practitioners and geriatricians in particular, should promote the abstinence from smoking as a behavioral norm for a correct life style. Non-smokers can delay the appearance of diseases and of the aging process, thus attaining longevity; further, non-smoking habit allows genetically predisposed subjects to reach the extreme longevity and maintain an acceptable health status and autosufficiency.

Increased circulating Interleukin-18 levels in centenarians with no signs of vascular disease: another paradox of longevity?

Interleukin (IL)-18 is highly expressed in macrophages from human atherosclerotic plaques, suggesting its involvement in ischemic syndromes. We evaluated IL-18 and IL-18 binding protein (BP) in healthy centenarians, as longevity is characterized by a reduced incidence of ischemic events. For comparison, patients with chronic ischemic syndromes (CIS) were evaluated. Serum IL-18 and IL-18BP levels were measured by non-cross-reacting ELISA in 16 healthy centenarians and in two age-control populations, each of 18 healthy individuals aged 55.9+/-1.43 and 74.3+/-1.35, respectively, as well as in 23 CIS patients, and another cohort of 23 healthy subjects that were age- and sex-matched with CIS patients. Centenarians displayed significantly higher total IL-18 serum levels compared to each control group. Elevated IL-18 levels were also present in CIS patients. However, centenarians had a significant higher level of IL-18BP compared to the cohort of 23 controls (P=0.0014), and compared to CIS patients (P=0.043); as a result centenarians exhibited a lower level of free IL-18 than CIS patients. The present results indicate that quenching of IL-18 by IL-18BP may explain the apparent paradox of elevated serum IL-18 with no vascular signs in centenarians.

Age-related modifications in circulating IL-15 levels in humans.

Aging is associated to a progressive establishing of a chronic inflammatory state linked to a continuous long exposure to antigens. Since IL-15 stimulates the proliferation of memory T cells and the immunosenescence is characterized by accumulation of memory T cells and exhaustion of naive T cells, we analyzed IL-15 levels in sera from 30 ultralongeval subjects with respect to those from young and old adults. IL-15 levels were assayed by immunoenzymatic methods. Ultralongeval subjects displayed significantly higher IL-15 levels with respect to both young and old controls. No statistical difference was found between old and young controls. These findings may explain, at least in part, the characteristic increase of memory cells in immunosenescence and the capacity of the immune system of centenarians to defend itself from infections through immune-inflammatory responses.

Candesartan cilexetil-induced severe hepatotoxicity

We report a case of severe hepatotoxicity associated with ductopenia in a 61-year-old woman. The patient developed jaundice, vomiting, and abdominal pain a few weeks after the beginning of treatment with candesartan cilexetil, 16 mg/d, for essential hypertension. Liver biopsy showed parenchymal bilirubinostasis with portal cholangitis and ductopenia. The drug was immediately withdrawn, and in the following weeks, aminotransferases and serum bilirubin returned to normal levels. The clinical-histologic data and the exclusion of known causes of liver disease led us to make a diagnosis of drug-induced cholestasis. To our knowledge, this is the first description of severe hepatotoxicity associated with ductopenia caused by an adverse reaction to candesartan cilexetil.

Effect of levodopa on interleukin-15 and RANTES circulating levels in patients affected by Parkinson's disease.

Parkinsons disease (PD) is an extra-pyramidal neurodegenerative disorder, in which alterations of the immune system are involved. Interleukin (IL)-15 stimulates cellular immune response and induces growth and differentiation of various immune cells. RANTES, promoting leukocyte infiltration to sites of inflammation, mediates the trafficking and homing of immune cells. To clarify the potential effect of levodopa on the immunological network of PD, we analyzed IL-15 and RANTES serum levels in PD patients, treated or not with levodopa, and in healthy donors. Levodopa-treated patients showed significantly higher IL-15 and RANTES circulating levels with respect to healthy controls and higher, although not significantly, levels with respect to untreated patients. So, we hypothesize that the immunological alterations found in PD may be linked, at least in part, to levodopa therapy.

Lower platelet count in healthy centenarians correlates with dispersion of the QT interval.

Background and aims: Centenarians display a lower incidence of vascular ischemic events. A high platelet count and increased QT dispersion (QTd) represents a risk factor for cardiovascular events. The aim of this study was to evaluate platelet count and QTd in healthy centenarians and to establish correlations between these two indices. Methods: 16 healthy centenarians (4 males, 12 females, range 100–105 years) living in a municipality of Eastern Sicily, and 40 healthy control subjects, divided into two groups: group A (N=20), age range 45–65 years, 7 males, 13 females; and group B (N=20), range 65–85 years, 6 males, 14 females, were examined. Platelets were counted using a blood analyzer and QTd was measured in standard 12-lead electrocardiograms. Differences in platelet count were assessed by one-way analysis of variance (ANOVA) and the Bonferroni test. Correlation coefficients between platelet count and QTd were calculated with the Spearman rank test. Results: Centenarians showed a lower platelet count compared with controls, which was significant with respect to older controls, group B (p<0.05). QTd values did not significantly differ between centenarians and controls. A significant correlation between QTd and platelet count was evident in centenarians but not in controls. This correlation became evident in control subjects with a platelet count ≤240000/mm3. Conclusions: We hypothesize that a reduced number of platelets and the maintenance of normal QTd may contribute to extreme longevity and protect centenarians from cardiovascular events.

Smoking, health and ageing.

On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related diseases was held in Palermo, Italy. Here, the lecture of V. Nicita-Mauro on Smoking, health and ageing is summarized. Smoking represents an important ageing accelerator, both directly by triggering ana inflammatory responses, and indirectly by favoring the occurrence of several diseases where smoking is a recognized risk factor. Hence, non-smokers can delay the appearance of diseases and of ageing process, so attaining longevity.