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Recent clinical trials in hormone therapy (HT) for women appronching or past menopause have been disappointing. Most women who have been taking conjugated equine estrogens combined with synthetic progestins have been encouraged to stop these supplements because of increased health risks. The results of the clinical trials may be accurate about the risks associated with the synthetic compounds and combinations, but the data do not reflect what might have been the case if 17β-estradiol had been tested with natural progesterone instead of synthetic medroxyprogesterone acetate. For the most part, in almost all work on HT, estrogens have been given the primary focus despite the fact that progesterone has important properties that can enhance the repair of neurodegenerative and traumatic injuries to the central nervous system. This article reviews some of those properties and discusses the evidence suggesting that, if HT is to be reconsidered, progesterone should be given more attention as a potent neurotrophic agent that may play an important role in reducing or preventing motor, cognitive, and sensory impairments that can accompany senescence in both males and females. [ABSTRACT FROM AUTHOR]

In this review, we first briefly introduce the reader to our autoimmune hypothesis for the development of atherosclerosis based on experimental and clinical data. This hypothesis postulates that humoral and cellular immunity against heat-shock protein 60 (HSP60), a phylogenetically highly conserved stress protein, is the mechanism that initiates atherogenesis. We then turn to our investigations of arterial specimens from children and young adults. These clearly show that mononuclear cell infiltrations of the intimal layer already occur before the emergence of clear-cut atherosclerotic lesions, a phenomenon we have termed vascular-associated lymphoid tissue (VALT). In early lesions analyzed within the framework of the Pathological Determinants of Atherosclerosis in Youth (PDAY) study, T lymphocytes proved to be a major cellular constituent. In the Bruneck Study, a large, prospective atherosclerosisprevention study in adults aged 40 years and older, we found a highly significant correlation between serum anti-HSP60 antibody titers and the occurrence and extent of sonographically demonstrable atherosclerotic lesions. However, no such correlation emerged with respect to HSP60-reactive T cells in the peripheral blood. In contrast, the similar Atherosclerosis Risk-Factors in Male Youngsters (ARMY) study, performed on 17- to 18-year-old volunteers, showed a highly statistically significant correlation between arterial intima-media thickening and HSP60 reactivity among peripheral T cells and (less pronounced) anti-HSP60 antibodies, even at this young age. We take this as indirect evidence that both T cell and B cell immunity against HSP60 plays a major role in the earliest stages of the disease. Because VALT can already be observed in healthy children and young adults, we hypothesize that T cells initiate the disease and that humoral antibodies play a facilitating, accelerating role. Finally, we provide initial evidence that smoking, as the most important risk factor for atherogenesis, also exerts its disease-inducing and disease-promoting effects by inducing HSP60 expression by vascular endothelial cells. [ABSTRACT FROM AUTHOR]

To test new treatment modalities, a pilot study with a novel noninvasive biophysical methodology (Delta-S DYD) that can artificially exert a "decrease of entropy" through the patented electromagnetic-driven delivery of "energy clusters" was designed. This process has been modulated and integrated by the body as a "self" source to support the energy-dependent functional stores, thus modifying reparative into regenerative mechanisms of liver parenchyma. Seven long-standing hepatitis C virus-positive (Child A-B) cirrhosis patients with overt symptoms and portal hypertension and failure or side effects of antiviral drug treatment underwent 40-mm sessions of Delta-S DVD daily for six months and were followed up monthly. At the end of the first month, rapid improvement of symptoms and a decease of portal hypertension were noted. At the end of treatment, all patients showed either a complete (80%) of a partial (20%)regression of fatigue (FISK score) peripheral edema pruritus and palmer erythema. As observed despite having stopped beta blockers, F1 esophageal varices disappeared (60%), whereas F2 decreased to F1. The Doppler ultrasound aspect of partial (40%) or total (20%) atrophy was either reduced (60%) or reverted to normal (20%), and the respiratory dynamics of the portal vein improved (80%) or normalized (20%), whereas gross scarring nodules disappeared in 40% of cases. These promising data pave the way for an innovative physiopathological approach with extensive clinical applications. [ABSTRACT FROM AUTHOR]

The purpose of this study is to test the prediction of the evolutionary theory of aging that human longevity comes with the cost of impaired reproductive success (higher infertility rates). Our validation study is based on the analysis of particularly reliable genealogical records for European aristocratic families using a logistic regression model with childlessness as a dependent (outcome) variable, and woman's life span, year of birth, age at marriage, husband's age at marriage, and husband's life span as independent (predictor) variables. We found that the woman's exceptional longevity did not increase her chances of being infertile. It appears that the previous reports by other authors of high infertility among long-lived women (up to 50% infertility) are related to incomplete data, that is, births of children not reported. Thus, the concept of the high cost of infertility for human longevity is not supported by the data when these data are carefully cross-checked, cleaned, and reanalyzed. [ABSTRACT FROM AUTHOR]

Little effort has been directed toward studying the relationship between morbidity and mortality at exceptional ages, perhaps for no better reason than it has been difficult to do given available data resources. Two study innovations/adjustments are required to adequately represent count data with reports of health from aged sample persons. These design features are oversampling of the exceptional group and linkage to detailed administrative reports. The National Long-Term Care Survey (NLTCS) has made it possible to study health and functioning in the context of exceptional longevity. [ABSTRACT FROM AUTHOR]

It is generally assumed that somatic mtDNA mutations are originally created in the cells where these mutations are currently found. Accumulating data indicate, however, that cells with a particular mtDNA mutation tend to "cluster," that is, occur repeatedly within a given sample, but not in the others. Clusters likely are clonal, which implies that mtDNA mutations do not originate in the cells that currently carry them, but rather in those cells' progenitors, such as stem or satellite cells, or even earlier in the development. Importantly, a majority of mtDNA mutations appear to belong to such clusters, and thus mutational events in progenitor cells may be one of the major sources of mtDNA mutations in healthy aging tissue. More research including the analysis of multiple samples per individual is needed to confirm the existence of clustering and to distinguish between the possible clustering mechanisms. [ABSTRACT FROM AUTHOR]

Heat shock protein (HSP) 47 is a specific chaperone of procollagen. This heat shock protein is responsible for the correct three-dimensional organization of procollagen and its control-quality prior secretion. The aim of the study is to evaluate the level of HSP 47 in aged, photoaged, and senescent fibroblasts and its modulation by a plant extract (Salix alba). The level of HSP 47 and/or procollagen expression in fibroblasts was measured by real-time RT-PCR (mRNA transcripts) and by flow cytometry (immunochemistry technique for measurement of arbitrary fluorescence intensity). Immunochemistry techniques and confocal microscopy were used to visualize the cellular localization of HSP 47 and procollagen. These parameters were compared with different age donors, nonsenescent, and senescent fibroblasts. Fibroblasts were irradiated by a noncytotoxic dose of UVA (6 J/cm²), and HSP 47 level was evaluated. S. alba extract was tested for its capacity to modulate HSP 47 expression. Colocalization of HSP 47 and procollagen was shown by confocal microscopy, indicating that HSP 47 could play a role of procollagen molecular chaperone in the cellular model. It was also shown that the HSP 47 level is decreased in old-donor cells, senescent, and irradiated cells. This decrease can be modulated by a S. alba extract (polyphenols rich) in a dose-dependent manner. The evaluation of HSP 47 expression in the experimental conditions can lead to a new approach of aging and photoaging, pointing out the implication of this chaperone in these pathophysiologic phenomena. Modulation of HSP 47 expression by this family of molecules could be of cosmetic and/or dermatologic interest. [ABSTRACT FROM AUTHOR]

Cytochemically evidenced cytochrome oxidase activity was morphometrically measured in the cerebellar cortex of adult and old rats. The ratio (R) between the area of the precipitate due to the cytochemical reaction and the overall area of each mitochondrion was calculated. While in adult rats an inverse correlation between mitochondrial size and R values (r = -.905) was envisaged, in old animals increasing values of R were paired by increases in mitochondrial area (r =.561). Paired-quartile comparisons of the R values from adult and old animals documented a marked age-related impairment of the mitochondrial metabolic competence in small (I quartile: -31.6%) and medium-sized (II quartile: -26.4; III quartile: -16.4) mitochondria, while large organelles showed the lowest age-related decrease (IV quartile: -3.0%). The present findings support that a marked dysfunction of small and medium-sized mitochondria contributes to the significant decay of energy metabolism currently reported in physiological aging. [ABSTRACT FROM AUTHOR]

We have proposed that normal food intake is geared toward optimizing the internal milieu for reproduction, despite some components of this milieu being detrimental to health. In dietary restriction, the animal is prevented from eating enough to attain or maintain reproductive capacity and this particular milieu does not materialize. Life extension occurs as a by-product. This idea provides a framework for exploring biomolecular changes in dietary restriction and their relevance to aging. Leptin is a case in point: here, a decrease in leptin level in dietary restriction is explored in the light of leptin's role in the complex signaling system of reproductive switch. [ABSTRACT FROM AUTHOR]

Information about several nutritional issues discussed at the conference "Foods for Health in the 21st Century: A Roadmap for the Future" at University of California, Davis is presented. The conference was hosted by scientist UC Davis. The conference was focused on future developments in nutrition and human health and addressed several health related issues including aging, cancer, immune responses, and allergies.

A preface for the April 2006 issue of the "Annals of the New York Academy of Sciences" is presented.