A family with hyperalphalipoproteinemia is described, being exceptional the longevity of some of their members. The proband, a 36 years-old woman with excellent health, showed total cholesterol levels of 6.77 mmol/l, HDL-cholesterol 3.00 mmol/l and apoprotein (apo) AI 2.4 g/l. HDL-cholesterol levels of her mother and two sisters were 1.86, 2.07 and 2.02 mmol/l, respectively. Their serum apo AI levels were 2.11, 2.32 and 2.30 g/l, respectively.
Centenarians are people who escaped from major common diseases, including cancer, and reached the extreme limits of human life-span. The analysis of demographic data indicates that cancer incidence and mortality show a levelling off around the age of 85-90 years, and suggests that oldest old people and centenarians are protected from cancer onset and progression.
Understanding mechanisms underlying longevity, and endeavor towards the specific goals of alleviating frailty in old age, require a comprehensive approach that considers the various theoretical and experimental approaches, as well as compiling the data on humans. This logistic has underlined the program of the conference, and is reflected in the present special issue. Considerable volume of data now point to distinct genes that are associated with exceptional longevity in humans, as reflected from the articles in this volume.
Subjects with exceptional longevity have a lower incidence and/or significant delay in the onset of age-related disease, and their family members may inherit biological factors that modulate aging processes and disease susceptibility. In a case control study, we aim to determine phenotype and genotype of exceptional longevity in a genetically homogenous population (Ashkenazi Jews), and their offspring, while an age-matched control group of Ashkenazi Jews was used as control groups.
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
BACKGROUND: High-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP) gene deficiency mutations that increase HDL-C levels have been associated with exceptional longevity. However, a recent clinical trial of a promising CETP inhibitor that markedly increases HDL-C was terminated due to increased mortality. In light of this controversy, we examined the relationship among HDL-C, CETP mutations, and longevity phenotypes in the long-lived Japanese-American men of the Honolulu Heart Program (HHP).
Romanian Journal of Internal Medicine = Revue Roumaine De MÈdecine Interne
Decreased high density lipoproteins (HDL) plasma levels are a recognized independent risk factor for atherosclerotic cardiovascular disease. Attempts were therefore initiated to pharmacologically raise plasma HDL cholesterol, and the most impressive increase was obtained by inhibiting cholesteryl ester transfer protein (CETP) by means of the synthetic compound torcetrapib. Clinical trials were however disappointing, as torcetrapib increased mortality and did not reduce the progression of atherosclerosis.
An epidemiological study was carried out among a random sample of women aged 18 to 69 years to examine possible determinants of plasma high density lipoprotein and total cholesterol (HDL-C and T-C). In a multiple regression analysis consumption of alcohol, fatty fish, and parental longevity showed positive associations with HDL-C, which were statistically significant. Smoking habit, sucrose consumption, and a family history of ischaemic heart disease showed significantly negative associations.
Changes in lipid metabolism with age result in lower total serum cholesterol and low-density lipoprotein concentrations. There is no evidence that longevity and lipid profiles are influenced by genetic make-up. It is difficult to establish an optimum total serum cholesterol in the elderly but values established in younger subjects give a guide. High-density lipoprotein may be even more protective in the elderly and could turn out to be a better predictor of coronary disease. Screening for the treatment of hypercholesterolaemia should be carried out in the elderly.