Luciano Motta

The extreme longevity: the state of the art in Italy.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. The extreme longevity: The state of the art in italy Claudio Franceschi, Luciano Motta, Massimo Motta, Giuseppina Candore, Calogero Caruso

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.

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.

Continuous subcutaneous insulin infusion: A long-term study

SummaryThe authors report data obtained from a 3-year study of CSII and humanized insulin (semi-synthetic human insulin) administered to 18 insulin-dependent subjects in the outpatient clinic. The aim of this study was to evaluate the validity of insulin pumps in long-term treatment. Metabolic parameters were significantly improved (p<0.001) in the first month and remained so with only slight alterations throughout treatment. The authors underline some metabolic problems (ketosis) caused by malfunctioning of the insulin pumps, by the difficulties with the infusion sytem or by nodular skin lesions at the infusion site. Only these lesions called for treatment to be discontinued in 4 patients. The highest incidence of nodular skin lesions was seen after one year’s uninterrupted treatment and they seem connected to the duration of treatment rather than to the patients’ negligence (inadequate hygiene, delayed needle substitution). The authors conclude that CSII treatment is valid over short-term periods, whereas it presents drawbacks over long-term administration.

COGNITIVE DETERIORATION IN ELDERLY DIABETIC PATIENTS

Summary This study was aimed at evaluating the cerebral alterations occurring in diabetic subjects. The total study population consisted of 29 males (mean age: 76.2 ± 6.3 years) and 40 females (mean age: 74.2 ± 8.6 years). The patients were divided in 3 groups: (i) Late onset elderly diabetics (15 patients of mean age 76.9 ± 7.6 years, onset of diabetes at 70 years of age); (ii) Early onset elderly diabetics (15 patients of mean age 74.4 ± 8.3 years, onset of diabetes at 46 years of age; (iii) Non-diabetic elderly controls (39 patients of mean age 74.5 ±7.7 years). The patients underwent psychometric testings by using the following methods: mini mental state examination (MMSE), geriatric depression scale (GDS), activity of daily living (ADL), instrumental activity of daily living (IADL); attentional matrix test (AMT), visuo-spatial span test (VSST) and verbal span test (VST). The results indicate that diabetes is apparently not influencing the cognitive performance. As regards the affective disorders, the late onset elderly diabetics display more depressive disorders than the other 2 groups of patients studied.

Cardiac and renal function during treatment with lisinopril plus nitrendipine in elderly patients with severe hypertension

The effectiveness of a combination of nitrendipine plus lisinopril in preventing renal damage was evaluated for a 12-month period in 20 elderly patients with severe hypertension. Results showed no significant changes in glomerular filtration rate (GFR) but a significant decrease in microalbuminuria; 24-hour diuresis and 24-hour natriuresis were significantly increased after 6 months. These changes persisted until the end of the study. Mean 24-hour ambulatory blood pressure measurements, recorded every 2 months, decreased to normal values starting at month 2; blood pressure control was maintained through the remainder of the study. Left ventricular mass index, interventricular septum thickness, posterior wall thickness, and left ventricular diastolic diameter were also significantly reduced compared with baseline values at 6 months. We conclude that the nitrendipine/lisinopril combination showed beneficial therapeutic effects on blood pressure control, as well as on cardiac and renal function in elderly patients with severe hypertension.

Glomerular hyperfiltration indicates organ damage in essential hypertension

Abstract In 80 patients with essential, mild to moderate, recent ( 99 Tc ml/min × 1.73 m 2 ; left ventricular mass and diastolic filling were determined by guided M-Mode echocardiography and by early-to-late mitral inflow velocity ratio (E/A), calculated by Doppler echocardiography. Results showed a significant increase of left ventricular mass index and E/A in hyperfiltrant patients. We concluded that a high GFR can be an indicator for early target organ damage in patients with recently diagnosed essential hypertension and normal renal function.

Regolazione Della Secrezione Dell’ormone Somatotropo: Tentativo Di Interpretazione Unitaria

RiassuntoGli AA. prendono in esame i varî aspetti della secrezione somatotropinica: su essa influiscono i substrati energetici, quali glucosio, NEFA e proteine (regolazione di tipo metabolico), e meccanismi di tipo catecolaminico (stress, vasopressina, pirogeni, L-dopa); è presente inoltre una secrezione ritmica di GH, la quale si verifica, con meccanismo ancora non caratterizzato, in rapporto al sonno (SWS). Mentre la stimolazione di tipo metabolico può essere inibita con la contemporanea somministrazione di glucosio, ciò non avviene per la stimolazione di tipo catecolaminico e per quella legata al sonno. Sulla base di queste premesse e del presupposto che la regolazione della secrezione di GH avviene a livello diencefalico, gli AA. avanzano un’ipotesi di interpretazione unitaria del meccanismo di controllo della secrezione somatotropinica. Il segnale metabolico e quello catecolaminico verrebbero cioè percepiti in maniera indipendente, o meglio il secondo agirebbe a valle del primo, così da non poter essere influenzato, come questo, dalla iperglicemia. Viene supposta — cioè — la presenza di un chemocettore, sensible all’informazione energetica, che trasmette il segnale con meccanismo adrenergico. La ricezione, a livello della cellula GH-RF-secernente, avverrebbe mediante recettori α. Viene infine postulata una distribuzione topografica della regolazione metabolica nel diencefalo medio-posteriore (nucleo ventromediale) e di quella legata allo stress e al sonno nel diencefalo anteriore (nucleo paraventricolare).RésuméLes auteurs examinent les différents aspects de la sécrétion de somatotrophine: sur celle-ci se répercutent les sub-stratums energétiques, tels que glucose, NEFA et protéines (régulation de type métabolique), et les mécanismes de type catécholaminique (stress, vasoprexine, pyrogènes, L-dopa); une sécrétion rythmique de GH est aussi présente; celle-ci se produit, par un mécanisme pas encore caractérisé, en relation au sommeil (SWS). La stimulation de type métabolique peut être interdite par l’administration contemporaine de glucose, tandis que cela ne se vérifie pas pour la stimulation de type catécholaminique et pour celle liée au sommeil. Sur la base de cette introduction et partant du principe que la régulation de la sécrétion de GH se produit au niveau diencéphalique, les auteurs avancent l’hypothèse de l’interprétation unitaire du mécanisme de contrôle de la sécrétion de somatotropine. Les signaux métabolique et catécholaminique seraient donc perçus d’une manière indépendante, ou mieux encore le deuxième agirait en aval du premier, de sorte à ne pouvoir être influencé, comme celui-ci, par l’hyperglycémie. On suppose donc la présence d’un «chemocepteur», sensible à l’information enérgétique, transmettant le signal par un mécanisme adrénergique. La réception, au niveau de la cellule GH-RF-sécrétante, se produirait par des récepteurs α. On postule enfin une distribution topographique de la régulation métabolique dans le diencéphale moyen-postérieur (noyau ventromédial) et de celle liée au stress et au sommeil dans le diencéphale antérieur (noyau paraventriculaire).ResumenLos autores examinan diversos aspectos de la secreción somatotropínica: en ella influyen substratos energéticos, tales como la glucosa, los ácidos grasos libres y las proteínas (regulación de tipo metabólico), y otros mecanismos de tipo catecolamínico (stress, vasopresina, pirógenos, L-dopa); se halla presente también una secreción rítmica de GH, la cual se verifica, a través de un mecanismo que todavía no ha sido caracterizado, en relación con el sueño (SWS). Mientras la estimulación de tipo metabólico puede ser inhibida con el suministro simultáneo de glucosa, no acontece lo mismo con la estimulación de tipo catecolamínico y con la vinculada al sueño. Sobre la base de esas premisas y previo presupuesto de que la regulación de la secreción de GH tiene lugar a nivel del diencéfalo, los autores avanzan una hipótesis de interpretación unitaria del mecanismo de control de la secreción somatotropínica. Es decir, que la señal metabólica y la catecolamínica serían percibidas de manera independiente o, mejor aún, la segunda actuaría debajo de la primera, sin poder, por tanto, recibir influencia por parte de la hiperglicemia, tal como le sucede a la primera. O sea, que se supone la existencia de un quemioceptor sensible a la información energética que transmite la señal con mecanismo adrenérgico. La recepción a nivel de la célula GH-RF-secretora, tendría lugar por medio de receptores α. Finalmente se formula la distribución topográfica de la regulación metabólica en el diencéfalo medioposterior (núcleo ventrículomedial) y la vinculada al sttess y al sueño en el diencéfalo anterior (núcleo paraventricular).ZusammenfassungDie Verfasser besprechen die verschiedenen Aspekte der Somatotropinsekretion: sie wird sowhol von Energiesubstraten wie Glukose, FFA und Proteinen beeinflusst (Regulierung vom metabolischen Typus), als auch von an Katecholamine gebundenen Mechanismen (Stress, Vasopressin, Pyrogene, L-Dopa); daneben findet sich noch eine rhythmische GH-Sekretion, deren Mechanismus noch nicht geklärt ist, im Zusammenhang mit SW-Schlaf. Während die Stimulierung vom metabolischen Typus durch gleichzeitige Verabreichung von Glukose gehemmt werden kann, ist dies für die Stimulierung vom Katecholamin-Typus und für die an den Schlaf gebundene nicht möglich. Aufgrund dieser Tatsachen und in der Annahme, dass die Regulierung der GH-Sekretion im Zwischenhirn erfolgt, setzen die Verfasser eine Hypothese zur einheitlichen Interpretation des Kontrollmechanismus der Somatotropinsekretion auseinander. Es wird angenommen, dass das metabolische und das Katecholamin-Signal unabhänging von einander empfangen werden, oder besser, dass letzteres talwärts vom ersterem wirkt, weshalb es auch, im Gegensatz zu diesem, nicht durch Hyperglykämie beeinflusst werden kann. Mit anderen Worten, es wird ein Chemozeptor angenommen, welcher für Informationen über Energiesubstrate empfindlich ist und das Signal durch einen adrenergenen Mechanismus überträgt. Der Empfang des Signals in der GH-RF-sezernierenden Zelle soll durch alpha-Rezeptoren erfolgen. Schliesslich wird folgende topographische Verteilung der Regulationszentren gefordert: die metabolische Regulation im mittleren-hinteren Zwischenhirn (Nucleus ventromedialis), die an Stress und Schlaf gebundene im vorderen Zwischenhirn (Nucleus paraventricularis).SummaryThe various aspects of growth hormone secretion are considered: it is subject to the influence of the energy substrates, such as glucose, NEFA and proteins (metabolic regulation) and to catecholamine mechanisms (stress, vasopressin, pyrogens, L-dopa); there is also a rhythmic secretion of GH, the mechanism of which is as yet undefined, related to sleep (SWS). While metabolic stimulation can be inhibited by simultaneous glucose administration, this is not so for catecholamine- or sleep-related stimulation. On the basis of these premises and of the assumption that GH secretion is regulated at the diencephalic level, a comprehensive hypothesis interpreting the control mechanism of growth hormone secretion is set out. It is suggested that the metabolic signal and the catecholamine signal are picked up independently, or rather that the second acts at a lower level than the first, so that contrary to the first it cannot be influenced by hyperglycemia. In other words the existence of a chemoreceptor is postulated which would be sensitive to information concerning energy substrates and would transmit the signal by an adrenergic mechanism. Reception in the GH-RF-secreting cell would be by α-receptors. As to topographical distribution, it is suggested that metabolic control occurs in the middle-posterior diencephalon (ventromedial nucleus) and the stress-and sleep-related control in the anterior diencephalon (paraventricular nucleus).