2005

Dtsch Med Wochenschr. 2005 Apr 29;130(17):1061-6.
[Significance of biomarkers for metabolic syndrome during weight reduction].[Article in German].
Rochlitz H, Akpulat S, Bobbert T, Mai K, Mohlig M, Osterhoff M, Weickert MO, Pfeiffer AF, Spranger J.
Deutsches Institut fur Ernahrungsforschung Potsdam, Nuthetal und Abteilung fur Endokrinologie, Diabetes und Ernahrungsmedizin, Charite-Universitatsmedizin Berlin, Campus Benjamin Franklin, Deutschland

INTRODUCTION: Obesity is a risk factor for type 2 diabetes, hypertension, dyslipidemia and cardiovascular disease. We aimed to analyse the changes of parameters of the metabolic syndrome and to investigate which markers are useful in the prediction of a successful weight loss. Preliminary data of an ongoing study are presented. METHODS: 18 obese individuals (15 female, 3 male, mean age 50.9 years, mean BMI 36.1) finished a 12 month weight loss program. This weight loss program was based on a hypocaloric diet (50 % carbohydrates, 30 % fat, 20 % protein) and at least 60 min physical activity per week. At baseline, 6 months and 12 months physical examination, indirect calorimetry, bioimpedance analysis were performed and blood was taken for routine laboratory. An oral glucose tolerance test and an euglycemic hyperinsulinemic clamp (n = 13) were carried out at baseline and after 6 months. RESULTS: There was a decrease of the BMI (+/- SEM) from 36.1 +/- 1.3 to 33.4 +/- 1.2 after 6 months and 32.8 +/- 1.3 after 12 months. Waist circumference (-8.8 cm), fasting blood glucose (98.0 to 91.2 and 92.5 mg/dl) and HDL cholesterol (47.2 to 64.6 mg/dl after 12 months) improved significantly. Other parameters of the metabolic syndrome (blood pressure, lipids, insulin resistance) and adiponectin improved slightly, but changes failed to be significant. In a linear regression analysis age, insulin resistance (M-value) and adiponectin at baseline were significant and independent predictors of a successful weight loss. CONCLUSION: In conclusion, most parameters of the metabolic syndrome improved after successful weight reduction, although changes of most parameters were modest and did not reach statistical significance.

2003

Adv Gerontol. 2003;12:57-76.
[Biochemistry of lifespan extension].[Article in Russian].
Golubev AG.
Research Institute of Experimental Medicine, 12 Akademika Pavlova Str., 197376, Saint-Petersburg, Russia.

A review of biochemical mechanisms underlying the known approaches to extension of lifespan and/or slowing down of ageing suggests that they all modify balances between generation of active oxygen and carbonyl species and the mechanisms that protect from their damaging effects or repair their consequences. A likely common target of the geroprotector effects of antioxidants, melatonin, and antidiabetic biguanides is the mitochondrial respiratory chain. In biological species that evolved through r-selection (nematodes, fruit flies, mice, and rats), the balance between anabolic/reproductive and self-maintenance/protective functions is the most significant modifiable factor of longevity and ageing. At the molecular level, the pivot of this balance is formed by the forkhead-type transfactors, whereas at the physiological level the balance is determined by dietary calories and physical activity via mechanism in which the central role is played by insuline-like peptides and, also, growth hormone and leptin or their functional analogs. In biological species that evolved through K-selection (higher primates, particularly humans), the latter balance is less important, and the biochemical factors of aging are more refracted through the higher regulatory systems, of which the most significant are catecholaminergic mechanisms of regulation of neuroendocrine-immune interrelationships and the circulatory system. This results in a decreased geroprotector potential of calory restriction and in an increased importance of the optimal physical activity. When these conclusions are compared with demographic data, it comes out that virtually all advances in gerontology may be reduced to maxims of healthy ageing known from extreme antiquity. Under optimal socioeconomic conditions, the chances to approach the documented world record of human longevity (122 years) may be increased by (not to mention getting rid of smoking and other abuses) high physical activity, adequate nutrition enriched in fresh fruits, optimism, and timely treatment of specific diseases. The most important bottleneck in the realization of these reserves is currently the public consciousness rather than the science.

2001

Exp Gerontol 2001 Jul;36(7):1025-34.
Strategy for identifying biomarkers of aging in long-lived species.
Ingram DK, Nakamura E, Smucny D, Roth GS, Lane MA.
Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. doni@vax.grc.nia.nih.gov

If effective anti-aging interventions are to be identified for human application, then the development of reliable and valid biomarkers of aging are essential for this progress. Despite the apparent demand for such gerotechnology, biomarker research has become a controversial pursuit. Much of the controversy has emerged from a lack of consensus on terminology and standards for evaluating the reliability and validity of candidate biomarkers. The initiation of longitudinal studies of aging in long-lived non-human primates has provided an opportunity for establishing the reliability and validity of biomarkers of aging potentially suitable for human studies. From the primate study initiated in 1987 at the National Institute on Aging (NIA), the following criteria for defining a biomarker of aging have been offered: (1) significant cross-sectional correlation with age; (2) significant longitudinal change in the same direction as the cross-sectional correlation; (3) significant stability of individual differences over time. These criteria relate to both reliability and validity. However, the process of validating a candidate biomarker requires a greater standard of proof. Ideally, the rate of change in a biomarker of aging should be predictive of lifespan. In short-lived species, such as rodents, populations differing in lifespan can be identified, such as different strains of rodents or groups on different diets, such as those subjected to calorie restriction (CR), which live markedly longer. However, in the NIA primate study, the objective is to demonstrate that CR retards the rate of aging and increases lifespan. In the absence of lifespan data associated with CR in primates, validation of biomarkers of aging must rely on other strategies of proof. With this challenge, we have offered the following strategy: If a candidate biomarker is a valid measure of the rate of aging, then the rate of age-related change in the biomarker should be proportional to differences in lifespan among related species. Thus, for example, the rate of change in a candidate biomarker of aging in chimpanzees should be twice that of humans (60 vs 120 years maximum lifespan); in rhesus monkeys three times that of humans (40 vs 120 years maximum lifespan). The realization of this strategy will be aided by developing a primate aging database, a project that was recently launched in cooperation with the NIA, the National Center for Research Resources, and the University of Wisconsin Regional Primate Research Center.

East Mediterr Health J. 2001 Jul-Sep;7(4-5):697-706.
New biochemical markers in chronic heart failure.
el-Bindary EM, Darwish AZ.
Department of Physiology, Tanta Faculty of Medicine, University of Tanta, Tanta, Egypt.

We investigated the plasma levels of tumour necrosis factor-alpha (TNF-alpha), leptin and insulin, and their relation to body mass index (BMI) in 80 male patients who presented with chronic heart failure (mean age: 47 +/- 4 years) at Tanta University Hospital. Plasma leptin, TNF-alpha and insulin were significantly increased and BMI significantly decreased in New York Heart Association classes III and IV patients. TNF-alpha, leptin and insulin were positively correlated, and TNF-alpha and BMI and leptin and BMI were negatively correlated in stages III and IV of heart failure. We conclude that cytokine neuroendocrine activation may form part of advanced stage heart failure. It may also be responsible for worsening cachexia, and can be used as a marker to determine disease severity.

1997

J Clin Endocrinol Metab 1997 Jul;82(7):2093-6.
Dehydroepiandrosterone sulfate: a biomarker of primate aging slowed by calorie restriction.
Lane MA; Ingram DK; Ball SS; Roth GS.
Gerontology Research Center, Nathan W. Shock Laboratories, National Institutes of Health, Johns Hopkins University Bayview Campus, Baltimore, Maryland 21224, USA.

The adrenal steroids, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), have attracted attention for their possible antiaging effects. DHEAS levels in humans decline markedly with age, suggesting the potential importance of this parameter as a biomarker of aging. Here we report that, as seen in humans, male and female rhesus monkeys exhibit a steady, age-related decline in serum DHEAS. This decline meets several criteria for a biomarker of aging, including cross-sectional and longitudinal linear decreases with age and significant stability of individual differences over time. In addition, the proportional age-related loss of DHEAS in rhesus monkeys is over twice the rate of decline observed in humans. Most important is the finding that, in rhesus monkeys, calorie restriction, which extends life span and retards aging in laboratory rodents, slows the postmaturational decline in serum DHEAS levels. This represents the first evidence that this nutritional intervention has the potential to alter aspects of postmaturational aging in a long-lived species.