Age-associated Variations Research Articles

Association between age and the utilization of radiotherapy in Ontario

Purpose: The purpose of this study was to assess whether: (i) radiotherapy (RT) utilization varies with age in Ontario cancer patients; (ii) age-associated differences in the use of RT (if they exist) vary with cancer site and treatment intent; (iii) the age-associated variation in RT utilization is comparable to the decline in functional status in the general population; and (iv) the variation with age is due to differences in referral to a cancer center or to subsequent decisions. Methods and Materials: Details for several cancer sites diagnosed between 1984–1994 were obtained from the Ontario Cancer Registry (OCR). RT records from all treatment centers were linked to the OCR database. Information about the functional status of the Canadian population was obtained from the 1994 National Population Health Survey conducted by Statistics Canada. Results: The rate of RT use declined with age, particularly for adjuvant and palliative indications. The relative decline in RT with age exceeded the relative decline in functional status with age in the general population. Most of the decline in RT use was related to a decline in referral to cancer centers. Conclusions: The referral for, and use of, palliative and adjuvant RT decreases more with age than can be explained by age-associated decline in functional status observed in the general population.

Automated analysis of blood samples from thoroughbred horses with the abbott cell DYN 3500 (CD3500) haematology analyser

This paper reports an evaluation of the Abbott CD35OO instrument in the haematological analysis of blood samples from 277 thoroughbred horses and foals. The age range studied was 20 days to more than 4 years, and CD35OO data were compared to those obtained from both the Coulter S88O and manual determinations of the leucocyte differential. The results showed excellent agreement (p>0.965) between the CD35OO and the S880 instruments for haemoglobin concentration, red blood cell (RBC) count, mean cell volume (MCV) and haematocrit (Hct). For the RBC count and MCV, however, the CD35OO gave slightly lower values than the S880 in the lower range of values and higher counts in the higher range of values. Correlations between the two automated platelet counts were acceptable although there was poorer agreement for platelet counts at higher (>250×109/1) values. In addition, some equine samples showed a higher CD35OO optical (WOC) compared to impedance (WIC) white cell count. This was shown to be due to the presence of lyse-resistant red cells, and further studies confirmed that the CD3500 resistant red cell mode was appropriate for analysis in such circumstances. Correlations between the CD3500 automated and manual differentials were also very acceptable with good correlations being obtained for granulocytes and eosinophils. Absolute CD3500 lymphocyte and monocyte numbers were however respectively lower and higher than determined by the reference procedure even though the total mononuclear cell (lymphocytes plus monocytes) count compared very well. Examination of age-associated variation for the RBC indices in this series of equine samples showed that the red cell count tended to be lowest in the older horses. In addition, there was also a clear trend for increasing MCV and decreasing red blood cell distribution width (RDW) values with progressive age in horses aged one year or older, with the values of these two indices being inversely related. Interestingly, this relationship was reversed in foals whereby during the first part of life, horses showed a decreasing MCV and an increasing RDW with progressive ageing up one year. These results confirm that the CD3500 analyser is well-suited to the analysis of blood samples from both foals and adult thoroughbred horses, and that the automated determination of leucocyte differentials in particular represents a significant advance in veterinary laboratory haematology.

Sex Hormones and Age: A Cross-sectional Study of Testosterone and Estradiol and Their Bioavailable Fractions in Community-dwelling Men

The role of endogenous sex hormones in many diseases makes understanding factors that influence levels of these hormones increasingly important. This study examined age-associated variations in total and bioavailable testosterone and estradiol levels among community-dwelling Caucasian men in Rancho Bernardo, California. Plasma samples obtained from 810 men aged 24-90 years in 1984-1987 were analyzed in 1993 using radioimmunoassay. Analyses of age-hormone associations, adjusting for weight, body mass index, alcohol ingestion, smoking, physical activity, caffeine intake, specimen storage time, and disease status, were undertaken. Bioavailable testosterone and bioavailable estradiol levels decreased significantly with age independently of covariates. Total testosterone and estradiol levels decreased with age only when analyses were controlled for confounders. The importance of the age-associated decline in endogenous sex hormone levels, particularly levels of bioavailable testosterone and bioavailable estradiol, and their relation to disease and function in men deserve further research.

Lipofuscin as a record of "rate of living" in an aquatic poikilotherm.

As an integral of oxidative metabolism and physiological age index, lipofuscin accumulation was used to evaluate assumptions underlying previous rejection of the rate of living theory of aging. Lipofuscin in the olfactory lobe cell mass of crayfish, Cherax quadricarinatus, was measured throughout life under a wide range of temperature regimes, using image analysis of fluorescence micrographs of brain sections. The relationship between temperature, chronological age, and rate of living, as indicated by lipofuscin accumulation rate, had a complex nonlinear three-dimensional structure, suggesting a thermal optimum, thermal mid-range metabolic compensation, and age-associated variation. The particular experimental window through which this response surface is viewed will have a profound effect on the outcome of life span experiments such as those previously used to test the rate of living theory. The results of this study further challenge assumptions leading to previous rejection of this theory.

Variations in Activity of the Human Natural Anti-Gal Antibody in Young and Elderly Populations

Anti-Gal is a natural antibody which constitutes approximately 1% of circulating IgG in humans and which interacts specifically with the mammalian carbohydrate epitope Gal alpha 1-3Gal beta 1-4GlcNAc-R (termed the alpha-galactosyl epitope). The purpose of this study was to determine whether there are age-associated changes in the affinity of anti-Gal in elderly individuals. The age-associated variations in affinity of anti-Gal were determined by the extent of this antibody binding to solid-phase alpha-galactosyl epitopes (mouse laminin) in ELISA, performed at various serum dilutions with serum samples from 140 elderly and 127 young individuals. The data were expressed as the mean of optical density (O.D.) values measured at serum dilutions of 1:40, 1:80, and 1:160, and correlated with the affinity of anti-Gal as measured in equilibrium dialysis. The proportion of individuals with low-affinity anti-Gal is sixfold higher in the elderly than in the young population. Whereas low-affinity binding of anti-Gal (mean O.D. value < or = 1.0) was observed in only 6% of the young population, as many as 35% of the elderly population displayed such low-affinity anti-Gal. Anti-Gal affinity in ELISA assay correlated with the affinity of this antibody as measured in equilibrium dialysis. The proportion of individuals with low affinity anti-Gal increases in the elderly population in comparison with the young population. The possible molecular mechanisms which may result in the age-associated decrease in the antibody affinity are discussed.

Modified Greulich-Pyle, Tanner-Whitehouse, and Roche-Wainer-Thissen (knee) methods for skeletal age assessment in a group of Italian children and adolescents

Modified Greulich-Pyle (GP), Tanner et al. 2, radius, ulna and short bones (TW2-RUS), TW2-20-bone and Roche-Wainer-Thissen RWT (knee) skeletal age assessments were made in an Italian population sample of 128 males and 93 females aged 4.1-16.9 years. All the scales appear to be well-suited to the Italian population despite minor differences. A very high correlation was found between the assessment of knee skeletal ages by the RWT method and that of the hand-wrist by the GP and TW2 systems in the same subject without sex and age-associated variations.

Differential Expression of Type IV Procollagen and Laminin Genes by Fetal vs Adult Skin Fibroblasts in Culture: Determination of Subunit mRNA Steady-State Levels

Basement membrane zone gene expression by fibroblast cultures, established from individuals varying in age from 14 fetal weeks to 61 years, was examined by molecular hybridizations with human sequence specific cDNAs corresponding to type IV procollagen and laminin subunit polypeptides. Northern transfer analysis with poly(A)+RNA revealed the presence of specific mRNA transcripts for alpha 1(IV) and alpha 2(IV) chains of type IV procollagen as well as B1 and B2 chains of laminin. Laminin A chain mRNAs were not detected using the same RNA preparations. Quantitative estimates of the steady-state levels of type IV procollagen and laminin mRNAs indicated that they were of relatively low abundance, as compared with mRNA to type I procollagen. The expression of alpha 1(IV) and alpha 2(IV) collagen genes was high in fetal fibroblasts but was reduced to low, yet detectable, levels in cultures established from 3-d to 61-year-old individuals. In contrast, the laminin B1 and B2 chain mRNA levels showed little age-associated variation within the cultures examined. These results provide evidence for differential regulation of the expression of different basement membrane zone macromolecules during chronologic aging.

T cell populations in the lacrimal gland during aging.

The present study examined the influence of age and gender on T cell populations in the lacrimal gland. Lacrimal (exorbital) glands were obtained from male and female rats at 19 days (pre-puberty), 9 weeks (adult) and 14 months (mid-life) of age and tissues were processed for T cell subset identification. In females, the density of total (W3/13+ and OX 19+), helper/inducer (W3/25+) and suppressor/cytotoxic (OX 8+) T cells underwent a significant increase in tissues from before, to after puberty. Following this rise, the density of all T cell populations decreased in glands from young adult to midlife females. This pattern of accumulation contrasted with the T cell profile presented by glands from males: T cell densities appeared unaffected from 19 days to 9 weeks of age, and then either declined (OX 19+, W3/25) or remained unchanged (W3/13+, OX 8+) in tissues of 14 month rats. An influence of gender on the distribution of T cells was also apparent if results were corrected for age-associated variations in lacrimal gland weight. Thus, the absolute number of all T cell populations rose dramatically in glands of both sexes from pre- to post-puberty. However, from 9 weeks to 14 months of age, the total content of W3/13+, OX 19+, W3/25+ and OX 8+ lymphocytes decreased 2-fold in glands of females, but did not vary in tissues of males. Of interest, the number of W3/25+ and OX 8+ cells was analagous in all age groups examined. Moreover, the combined total of W3/25+ and OX 8+ cells was greater than that of W3/13+ or OX 19+ cells at every age.(ABSTRACT TRUNCATED AT 250 WORDS)

Ageing studies in rat liver I. Complexity of RNA from two to ten months of age

A highly sensitive nucleic acid hybridization assay was used to compare the extent of nonrepetitive DNA transcription in rat liver between the ages of two and ten months. The basic approach consisted of initially purifying the DNA expressed in liver at these ages and then using it in reactions with homologous and heterologous RNAs. Such experiments failed to reveal any differences in nonrepetitive DNA transcription as a function of age. The possibility was also explored that there might be an age-associated variation in the proportion of the total RNA complexity attributable to poly(A+) RNA. These experiments, too, were negative in that the poly(A+) RNA was found in all cases to account for approximately 50% of the total sequence diversity. Overall, these data strongly suggest that ageing is not accompanied by a steady, progressive change in the regions of the genome transcribed, either quantitatively or qualitatively.

Morphometric differences between Australian wild rabbit populations

Morphometric distances, based on 20 skull measurements, were determined between eight localized Australian wild rabbit populations and a sample from the British Isles. To minimize the influence of age-associated variation in the Australian series, only animals estimated to be at least 12 months old (based on epiphyseal and dry eye-lens aging techniques) were included. Sexes were pooled after univariate and multivariate testing for sexual dimorphism and eliminating bizygomatic breadth. By means of univariate statistics, Mahalanobis generalized distance and canonical analysis, the various Australian and British Isles samples were shown to differ appreciably, morphometric distance increasing clinally in eastern Australia with geographic distance from the point of introduction (Geelong, Vic.). Based on a plot of first and second canonical variates, differences between three Canberra area samples were comparable in magnitude to those between certain populations separated by much greater geographic distances. These findings are consistent with results of studies of blood protein variations in Australian wild rabbit populations.