Calcium homeostasis and human evolution.

The maintenance of calcium homeostasis is critical to survival. The systems dependent upon the availability of calcium include the musculoskeletal, nervous, and immune systems, all of which utilize the ionic properties of divalent calcium to perform critical functions. The widespread utilization of calcium in essential biological processes across a wide range of phyla argues strongly for its adoption early in the evolution of life. In the broad context of evolution, the use of calcium in the structure of the skeleton is a relatively late, or derived trait. It is not surprising, therefore, that when conditions demand the resorption of bone to sustain normal blood calcium levels, resorption can lead to serious impairment of function. Nowhere is the force of natural selection greater than when traits essential to successful reproduction are directly involved. Thus, when the requirements of pregnancy and lactation demand it, major shifts in the endocrine regulation of calcium turnover occur. While beneficial to reproductive success, elements of these changes can have deleterious effects later in life. However, selective pressure on such traits diminishes with the years of remaining reproductive life. The genetic determinants of traits that only manifest their deleterious aspects after reproduction has ceased altogether are thus able to remain and even increase in frequency in the population's gene pool. Such traits have been designated antagonistic pleiotropies. The following discussion explores the possibilities of Type I osteoporosis, a condition experienced by many postmenopausal women being an example of antagonistic pleiotropy.

Fat or lean tissue mass: which one is the major determinant of bone mineral mass in healthy postmenopausal women?

The relative importance of fat and lean tissue mass in determining bone mineral mass among postmenopausal women was examined in this 1-year longitudinal study. Fifty postmenopausal Caucasian women entered the study; 45 of them completed a 1-year follow-up. Dual-energy X-ray absorptiometry was employed for measuring total and regional bone mineral density (BMD) and bone mineral content (BMC), fat tissue mass (FTM), lean tissue mass (LTM), and body weight. Results from linear regression analysis using the cross-sectional data (n = 50) of the study indicated that LTM explained a larger percentage of variation in bone mineral mass than did FTM. FTM and LTM were found to be moderately correlated (r = 0.55); when FTM was entered in the same predicting regression models, LTM was a significant predictor (p < 0.05) of the total and regional BMC, but not BMD. The percent FTM (and inversely %LTM) was correlated with BMD and BMC, but significant correlation was primarily found only for total body BMD (or BMC). Weight was the best predictor of total body BMD and BMC. Longitudinally (n = 45), annual changes in both FTM and weight were significantly associated with annual changes in regional BMD after adjustment for initial bone mineral values (p < 0.05). We conclude that bone mineral mass is more closely related to LTM than to FTM, while annual changes in regional BMD are more closely correlated with changes in FTM in healthy postmenopausal women. Meanwhile, increased body weight is significantly associated with increased bone mineral mass.

Trait shyness in the elderly: evidence for an association with Parkinson's disease in family members and biochemical correlates.

The emergence of potential treatments to slow the progression of idiopathic Parkinson's disease (PD) has increased the need for early identification of persons at risk. Although considered controversial, some prior studies indicate that PD patients may have premorbid histories of greater trait introversion or shyness as well as increased rates of disorders associated with shyness (e.g., anxiety, affective disorders, and irritable bowel syndrome). Essential features of trait shyness include (a) inhibited and avoidant behaviors and (b) physiological hyperreactivity to the novel or unfamiliar. In parallel, (a) depression in PD patients is associated with increased harm avoidance (a possible serotonergic function), and (b) PD patients have premorbid and comorbid decreases in novelty-seeking (a possible dopaminergic function). Taken together, previous research suggests the following hypotheses: (1) given evidence for marked heritability of shyness, shy elderly should report higher rates of PD in their family members than would nonshy elderly; and (2) shy elderly without PD should exhibit psychological and biologic characteristics similar to those reported in PD. Two groups, representing the top 27% (n = 37) and bottom 31% (n = 43) of scores on a standardized shyness scale, were drawn from a larger cohort of 138 older adults (ages 50-90) living in an active retirement community. Seventeen percent of the shy versus 2% of the nonshy reported PD in a family member or self (P < .05). Shy elderly were significantly more anxious (P < .01) and depressed (P < .05) than were the nonshy.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitization to early life stress and response to chemical odors in older adults.

This study examined the hypothesis that older persons who currently report illness from environmental chemical odors (cacosmia) may have experienced higher levels of stress early in life than did noncacosmic controls. The hypothesis derives from a time-dependent sensitization (TDS) model for cacosmia (Bell et al 1992) that predicts a relative interchangeability of stress and chemicals in inducing and eliciting sensitized responses in vulnerable individuals. Subjects were selected from those in the top 24% (cacosmic) and bottom 27% (noncacosmic) of a sample of 192 older adults (mean age 73.8 years) for self-reported frequency of illness form the odors of pesticide, car exhaust, paint, perfume, and new carpet. As in previous investigations, cacosmics were younger, more depressed, and more shy; cacosmics also included a higher proportion of women (83% versus 61%). As predicted, cacosmics rated themselves higher in stress for the first four decades of their lives, but not the recent past or present, even after controlling for depression, anxiety, hostility, shyness, age, and gender. Cacosmics reported increased prevalence of physician-diagnosed nasal allergies, breast cysts, hypothyroidism, sinusitis, food sensitivities, irritable bowel, and migraine headache. Only 4% of the overall sample (including 9% of the cacosmics) acknowledged the controversial physician diagnosis of "chemical sensitivity." The replicated observation of greater shyness in cacosmics is consistent with the ability of hyperreactivity to novelty to predict enhanced susceptibility to TDS from low levels of pharmacological agents in animals. The findings support a TDS model for cacosmia and suggest that cacosmia as a symptom identifies a large subset of the nonindustrial population with significant psychophysiological health problems that merit further objective examination.

Aging, bone loss, and the body mass index in Arizona retirees.

In order to identify relationships between changes in the body mass index (BMI) and those occurring in bone density with age, data from a sample of 2,075 Arizona retirees aged 60-90 years were compared by age and sex. Remodeling of the diaphysis of the radius follows a pattern that results in an increased diameter of the cortex and medullary cavity in both sexes. However, the resultant decrease in percentage cortical area (PCA) was greater in women than in men. The positive relationship between BMI and PCA is more pronounced in women, who begin to lose bone density earlier than men, and also lose it more rapidly. Despite the fact that average age at menopause is about 50 years and it is generally believed that bone loss slows within 5-10 years after menopause, average PCA values decline from 44% in 60-70 year old women to 37% in 80-90 year old Sun City women and to 36% in Tucson women. The decline in average PCA ranges from 45% in Sun City men and 46% in Tucson for 60-70 year old men to 43% and 42%, respectively, in 80-90 year olds. When the PCA values of women in four BMI categories are compared, cortical area increases with BMI, while medullary cavity values are similar across BMI categories. This relationship between BMI and PCA is much weaker in men. This pattern suggests more vigorous subperiosteal apposition in women with higher BMIs. Endosteal resorption does not seem to be as much affected by the BMI. An additional observation is that the BMIs of Sun City women are lower than those of Tucson women, although the decline in average values with age is very similar in the two populations, with a sharper decline from the 70-80 year group to the 80-90 year group than seen between the 60-70 year group and the 70-80 year group. Average BMIs of males are consistently higher than those of females in all age groups in the Sun City sample, but means for the sexes are very similar in the Tucsonans beyond 70 years. Sun City males of more advanced age are heavier than Tucson males, but the situation is reversed when women are similarly compared. © 1994 Wiley-Liss, Inc.

Possible time-dependent sensitization to xenobiotics: self-reported illness from chemical odors, foods, and opiate drugs in an older adult population.

The present paper summarizes key features of time-dependent sensitization (TDS) in neuropharmacology (progressive amplification of behavioral, neuronal, endocrine, and/or immune responses to repeated intermittent exposures to an environmental agent or cross-sensitizing agents) as a possible model for cacosmia (subjective sense of feeling ill from low levels of environmental chemical odors) in nonindustrial and industrial populations; and extends previous cacosmia research in nonpatient populations to an elderly sample. This study examined the symptom and psychological profiles of 263 older adults (aged 60-90 y, 71% women, 29% men); 57% reported that at least one chemical and 17% reported that at least four of five chemicals (pesticide, automobile exhaust, paint, new carpet, perfume) made them feel ill. Cacosmia ratings correlated weakly and negatively with age (r = -0.19, p = .001) over the whole sample. Cacosmia correlated significantly with self-reported illness from foods that may mobilize or generate opioid peptides (wheat, dairy, eggs) (r = 0.32, p < .0001) and with illness from opiate drugs (r = 0.23, p < .0001). When the sample was divided into four cells on the basis of above-versus below-median total chemical-induced illness score (CI) and total food-induced illness score (FI), the high CI and high FI, high CI only, and high FI only groups had more frequent indigestion, and the high CI group had more frequent difficulty concentrating than the groups below median for illness from both chemicals and foods (NOILL), even after covarying for age and anxiety. The most cacosmic subjects noted higher prevalence of physician-diagnosed allergies and irritable bowel than did noncacosmic subjects. In contrast with previous young adult cohort studies, the older illness groups did not differ with regard to sex distribution, depression, shyness, or repressive defensiveness. When considered with prior surveys of young adults, the present findings are consistent with the presence of previously established, time-dependent sensitization to multiple xenobiotic agents in susceptible individuals for whom psychological variables do not explain the symptom of cacosmia. If cacosmia is a symptom of TDS, then the neuropharmacology literature suggests the possibility of excitatory amino acid, hypothalamic-pituitary-adrenal axis, dopaminergic, and/or opioid involvement. Prospective studies with objective measures testing the possible induction of TDS to specific chemicals are indicated.

Body composition and longevity: is there a longevous morphotype?

Life expectancies are increasing in populations throughout the world. As infectious diseases decline as causes of mortality, certain degenerative diseases including cardiovascular disease and cancer account for an increasing percentage of deaths. As more people survive into old age, the intrinsic limits on the human life span will be reached. It is clear that genetic factors have a strong influence on the life span. It is not clear, however, that there are identifiable longevous body types (morphotypes). For the first time in human history, large numbers of people 80 years old and older are available for study. If there is an association between body form and composition and superior longevity, it should be possible to identify its major aspects. Monitoring changes in body composition throughout the life cycle and the retention of reserves to be drawn upon when disease or trauma threaten life may provide the basis for prediction of the course of life threatening diseases. The unusually high survival of morphotypes classifiable as "moderately obese" casts doubt on standards recommending "ideal weights for height" if the criterion in question is survival.

Stature loss among an older United States population and its relation to bone mineral status.

Age-related statural loss has been recorded but incompletely assessed in modern populations. In this study, data collected on stature during annual bone mineral assessments are analyzed for 1,024 Caucasian individuals from southern Arizona. Continued stabilization in reported maximum heights is seen in this population. With advancing age there is a gradual decrease in height apparently beginning in the mid-40s. Thereafter, there is a relatively rapid decrease in measured height. This contrasts to the much slower rates predicted from earlier populations (Trotter and Gleser: American Journal of Physical Anthropology 9:311-324, 1951). The rate of stature loss is associated with diminution of bone mineral density as well as with maximum height. Since there are suggestions of a secular trend toward greater reductions in bone mineral density, this study suggests there may be a secular trend toward an increase in statural loss with age.

Effects of aerobic training on exercise tolerance and echocardiographic dimensions in untrained postmenopausal women.

The cardiovascular effects of physical training were evaluated in a controlled trial involving 32 healthy, untrained, postmenopausal women. The subjects were randomly assigned to an aerobic exercise training program or a control group. The exercise group participated in at least three 40-minute supervised sessions per week for 8 months. Twenty-five subjects completed the study: eight in the control group and 17 in the training group. The training group had a significant increase over the training period in maximal oxygen consumption (27.3 +/- 4.6 ml/kg/min vs 30.8 +/- 5.4 ml/kg/min, p less than 0.05) and maximal treadmill exercise duration (9.8 +/- 2.6 minutes vs 11.3 +/- 2.2 minutes; p less than 0.05). The control group had no significant change in maximal treadmill exercise duration (9.0 +/- 1.2 minutes vs 9.2 +/- 1.4 minutes) but had a slight increase in maximal oxygen consumption (23.7 +/- 3.4 ml/kg/min vs 24.4 +/- 4.1 ml/kg/min, p less than 0.05). The training group had significant increases in M-mode echocardiographic left ventricular end-diastolic dimension (4.6 +/- 0.6 cm vs 4.8 +/- 0.4 cm, p less than 0.05) and calculated left ventricular ejection fraction (0.66 +/- 0.14 vs 0.74 +/- 0.12, p less than 0.05). M-mode echocardiograms demonstrated no significant change in left ventricular dimensions or wall thickness in the control group. In this group of untrained postmenopausal women, a training effect was associated with enhanced resting left ventricular ejection fraction and increased resting left ventricular end-diastolic dimension.

Association of early growth patterns with the process of aging.

In recent years, significant increases in life expectancy have occurred. This increase has been most pronounced among females. As a result, there were 156 women for every 100 men over age 75 years in the United States in 1970. The sexual disparity of life expectancies has increased throughout this century. The reasons for this trend are unknown. Males experience higher mortality rates in both infectious and degenerative diseases. The prognosis for a male patient is generally poorer no matter what the stage of the disease at the time of diagnosis or the course of treatment. It has been shown that the early stages of male growth and development are more susceptible to external perturbations. Thus, growth-maximizing diets have their greatest impact on male children. The connection between male responsiveness to environmental influences during early growth and vulnerability in the later years is significant to the understanding of the aging process.