Biological aging and the etiology of aneuploidy

A prevalent hypothesis concerning the cause of the rise in aneuploid conceptions with maternal age is that the changes that accompany normal ovarian aging increase the rate of meiotic errors in the oocyte. Biological aging of the ovary is accompanied by a decline in both the total oocyte pool and the number of antral follicles maturing per cycle, as well as changes in the levels of circulating reproductive hormones. The biological aging hypothesis predicts that aneuploidy rates should be higher in women with a prematurely reduced oocyte pool, and that women with trisomic conceptions should show signs of earlier ovarian aging than women of the same chronological age without trisomic conceptions. Comprehensive studies of aneuploidy in groups of women with known causes of premature ovarian failure remain to be done, though anecdotal evidence does suggest increased rates of pregnancy loss and aneuploidy. Smoking, which is a well-documented cause of earlier ovarian aging, is not associated with an increase in aneuploid conceptions. Evidence from women with unilateral ovariectomies is inconsistent. Support for the biological aging hypothesis was provided by one study showing that menopause occurred about a year earlier in women with a trisomic spontaneous abortion compared to women with chromosomally normal conceptions. Associations between high FSH and pregnancies with Down syndrome and chromosomally abnormal spontaneous abortions have also been reported. However, the most direct test of the hypothesis, which compared antral follicle counts and hormonal levels in women with trisomic pregnancies and those with chromosomally normal pregnancies, failed to find a difference in the expected direction. A prospective study of FSH levels in women with subfertility also failed to find an association with the rate of pregnancy loss. The bulk of evidence thus suggests that, if the processes of biological aging are indeed related to aneuploidy, they probably involve factors other than those measured by oocyte or antral follicle pool size and reproductive hormone levels.     

Compositional changes of the aortic valve similar to the artery with aging

To elucidate compositional changes of the cardiac valves with aging, the authors investigated the relationships among element contents in the aortic valves, in which the accumulation of calcium and phosphorus was the highest. The subjects consisted of 10 men and 14 women, ranging in age from 65 to 102 yr. Extremely significant direct correlations were found among the contents of calcium, phosphorus, magnesium, sodium, and zinc in the aortic valves. In contrast, significant inverse correlations were found between the contents of sulfur and the other elements, such as calcium, phosphorus, magnesium, and sodium. It should be noted that these correlations present in the aortic valves were very similar to those in the arteries, especially those in the thoracic aortas. The changes of the mass ratios of Mg/Ca and Mg/P in the aortic valves were similar to those in the thoracic aortas. As calcium and phosphorus increased in the aortic valve, the mass ratios Mg/Ca and Mg/P decreased reversely in the aortic valve. These results suggest that the compositional change of the aortic valve is very similar to that of the thoracic aorta.     

Ultrastructural changes in the dendrites during aging

Dendrite ultrastructure was studied in different brain areas of old rats, aged 28-30 months. Different ultrastructural forms of the reactive and destructive processes in the dendrites, irregularity of their pathomorphological changes with ageing and greater destruction of large dendrites, as compared to small ones are demonstrated.     

Architectural changes in the thymus of aging mice

Age-associated thymic involution is one of the most dramatic and ubiquitous changes in the immune system, although the precise mechanisms involved still remain obscured. Several hypotheses have been proposed incorporating extrinsic and intrinsic factors, however, changes in the thymic microenvironment itself is one of the least investigated. We therefore decided to undertake a detailed histological examination of the aging thymus in order to elucidate possible mechanisms of thymic atrophy. This investigation provides insight into the changes within the murine thymus with age, demonstrating a new approach to quantify protein expressional differences while preserving the thymic architecture. There is a decline in expression of thymic epithelial cell-specific makers and an increase in fibroblast content in the aging mouse thymus. This is concurrent with a disorganization of the thymic compartments, a morphological transformation within the epithelial cells and alterations of their archetypal staining patterns. Furthermore, this is linked to a rise in apoptotic cells and the novel finding of increased senescence in the thymus of older mice that appears to be colocalized in the epithelial compartment. These changes within the thymic epithelial cells may be in part accountable for thymic atrophy and responsible for the decline in T-cell output.     

The tolerance of the maxilla to blunt impact

This study reports the results of 38 infraorbital maxilla impacts performed on male cadavers. Impacts were performed using an unpadded, cylindrical impactor (3.2 kg) at velocities between 1 and 5 m/s. The peak force and acoustic emission data were used to develop a statistical relationship of fracture risk as a function of impact force. Acoustic emission sensors were used to provide a noncensored measure of the maxilla tolerance and were essential due to the increase in impactor force after fracture onset. Parametric and nonparametric techniques were used to estimate the risk of fracture tolerance. The nonparametric technique produced an estimated 50% risk of fracture between 970 and 1223 N. The results obtained from the parametric and nonparametric techniques were in good agreement. Peak force values achieved in this study were similar to those of previous work and were unaffected by impactor velocity. The results of this study suggest that an impact to the infraorbital maxilla is a load-limited event due to compromise of structural integrity.     

Passage-dependent changes in baboon endothelial cells--relevance to in vitro aging

In vitro cell culture system is a useful model for aging-related changes in a wide spectrum of biomedical research. In this study, we explored the passage and donor age-dependent changes in baboon macrovascular endothelial cells that are relevant to both in vitro cell culture aging models and experiments using cell culture techniques. We collected baboon femoral arterial samples from nine baboons ranging in age from 6 months to 30 years (equivalent to humans approximately 18 months to 90 years of age). We then cultured baboon femoral artery endothelial cells (BFAECs) in standard DMEM medium with 20% fetal calf serum with 1:3 split for subculture. Endothelial functions were documented by morphology, Dil-LDL uptake and expression of eNOS, MCP-1, vWF, VCAM-1, ICAM-1, and E-Selectin with or without cytokine stimulation. Most of the cells became nonmitotic after 30 population doublings, or 10 passages, when they became flattened, enlarged, and senescent. While it took approximately 3 days to reach confluence from three-dilution seeding at early passages (<6), confluence was not achieved even after 7 days of culture for cells after the 9th or 10th passage. There was a linear decline in eNOS expression with passage. However, this decline was significantly less in endothelial cells from a young baboon (6 months) than those from an old baboon (30 years). While basal expression of adhesion molecules was not changed with passaging, responses to cytokine stimulation appeared to be increased in later passaged cells. Our study has provided evidence for passage-related changes in key endothelial functions. The donor age-related differences in this in vitro aging process suggests that in vitro endothelial culture can serve as a biomarker for in vivo aging. Nonhuman primates can provide a model for investigating such aging-related biological characteristics.     

Biomarkers of aging in women and the rate of longitudinal changes

The purposes of this study were (1) to estimate biological age score (BAS) in Japanese healthy women based on the 4-7 years longitudinal data for physiological, hematological and biochemical examinations and (2) to examine the rate of aging changes in adult women based on the estimated BAS. The samples consisted of cross-sectional (n=981) and longitudinal (n=110) groups. Out of 31 variables examined, five variables (forced expiratory volume in 1.0 s, systolic blood pressure, mean corpuscular hemoglobin, glucose, albumin/globulin ratio) that met the following criteria: 1) significant cross-sectional correlation with age; 2) significant longitudinal change in the same direction as the cross-sectional correlation; and (3) assessment of redundancy, were selected as candidate biomarkers of aging. This variable set was then submitted into a principal component analysis, and the first principal component obtained from this analysis was used as an equation for assessing one's BAS. Individual BAS showed a high longitudinal stability of age-related changes, suggesting high predictive validity of our newly developed aging measurement equation. However, changes in the aging rate based on the estimated BAS were not constant. The mean slopes of the regression lines of BAS for the three age groups (age<45, 45相似文献   

Histological changes of the dopaminergic nigrostriatal system in aging

Although the maximum human lifespan has not increased in recent history, average life expectancy has risen dramatically since the beginning of the last century. Lengthening of lifespan has little merit if the quality of life is not preserved. In the elderly, the decline in memory and cognitive abilities is of great concern, as is motor weakening, which increases with age. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. Therefore, the aging of this system has both clinical and vocational aspects. This review includes studies quantitating age-related changes of the nigrostriatal system, with emphasis on the use of stereological methods, and provides tables of stereological studies performed in the nigrostriatal system.We acknowledge the Danish Parkinson Foundation and the Foundation of Stockbroker Henry Hansen and wife for financial support     

Compositional changes of the xiphoid process and costal cartilage with aging

Because zinc attenuates endothelial cell dysfunction that proceeds atherosclerosis, depressed zinc status may be involved in the initiation of endothelial dysfunction. However, before recommending a zinc-enriched diet to reduce the risks for atherosclerosis, the effect of excess zinc on endothelial cell functions in normozincemic status should be known. Therefore, in this study, the effect of dietary zinc on normal endothelial cell functions in animals subjected to a diet containing 334±58 ppm zinc for 30 d was studied to see whether supplemented zinc has an effect on endothelial cells. Despite a slight increase in blood zinc, unaltered aortic and kidney zinc contents were associated with unchanged blood pressure in rats subjected to a zinc-enriched diet. Increased basal nitric oxide and prostacyclin were accompanied by a normal response to phenylephrine. Dietary zinc influenced neither endothelial-dependent nor endothelial-independent relaxations significantly. However, it elevated the share of M1-type cholinoceptor response as well as dilator prostaglandin release, which seems to be nitric oxide dependent. There was a strong correlation (r=0.826, p<0.05) between M1-type cholinoceptor response and prostacyclin release in zinc-treated rings. These results suggested that zinc ions increases M1-mediated prostacyclin release in normal endothelial cells without altering intracellular pathways.     

Morphological changes in locus ceruleus of albino rats in relation to aging

Comparative studies were carried out under light, fluorescence- and electron-microscopic observations between young, adult and aged groups of albino rats with the following results: the neuronal packing density of locus ceruleus decreases with advanced age. In addition to the senescent loss of nerve cells, the surviving ones showed some shrinkage of perikarya and reduction or loss of Nissl substance. Some of them presented pyknosis, chromatolysis and loss of RNA in cytoplasm. Glial cells proliferated around the degenerating cells. Senescent cells showed an increase of heterochromatin and decrease of euchromatin. Changes in cytoplasmic organelles included the decrease of ribosomes, alterations in mitochondria and increase of lipofuscins. These senescent changes were thought to affect the absorption of nutrition, message exchange, protein synthesis, supply of energy and transport of materials by the nerve cells.