Aging as a consequence of selection to reduce the environmental risk of dying

Each animal in the Darwinian theater is exposed to a number of abiotic and biotic risk factors causing mortality. Several of these risk factors are intimately associated with the act of energy acquisition as such and with the amount of reserve the organism has available from this acquisition for overcoming temporary distress. Because a considerable fraction of an individual’s lifetime energy acquisition is spent on somatic maintenance, there is a close link between energy expenditure on somatic maintenance and mortality risk. Here, we show, by simple life-history theory reasoning backed up by empirical cohort survivorship data, how reduction of mortality risk might be achieved by restraining allocation to somatic maintenance, which enhances lifetime fitness but results in aging. Our results predict the ubiquitous presence of senescent individuals in a highly diverse group of natural animal populations, which may display constant, increasing, or decreasing mortality with age. This suggests that allocation to somatic maintenance is primarily tuned to expected life span by stabilizing selection and is not necessarily traded against reproductive effort or other traits. Due to this ubiquitous strategy of modulating the somatic maintenance budget so as to increase fitness under natural conditions, it follows that individuals kept in protected environments with very low environmental mortality risk will have their expected life span primarily defined by somatic damage accumulation mechanisms laid down by natural selection in the wild.

There is substantial empirical support for the notion that animals on average live far longer in a properly designed protected environment than in their natural environment (1–4). This implies that ecological risk factors are major determinants of life expectancy in the wild (5, 6), irrespective of variation in mortality risk with age (7) and of variation in the degree of senescence in wild animals (8–12). Regardless of intraspecies genetic and phenotypic variation and the huge interspecies variability in the repertoires of abiotic and biotic risk factors causing mortality in the wild, all individuals are faced with the destiny that one day, they will draw the fatal ticket in the Darwinian lottery. This raises the question of whether there exists a ubiquitous life-history strategy response to this ominous fact that is favored by natural selection.The hypothesis we will examine is that there exists such a life-history strategy, independent of temporal mortality risk profiles, which is materialized through a universal physiological principle of tuning the allocation to somatic maintenance to expected life span so that lifetime fitness is enhanced. The rationale for this is that an intimate link exists between the energy acquisition needs of an individual and mortality risk. Because somatic maintenance accounts for a substantial part of the lifetime need of acquired energy (13), restraining allocation to somatic maintenance from early on might reduce mortality risk because it allows either reduced energy acquisition activity or alternative use of the freed energy. Restraining the allocation to somatic maintenance incurs costs in terms of increasing somatic damage. However, as long as the accrued somatic damage is controlled in such a way that the costs do not materialize until rather late in life, when an individual would most probably already be dead, the penalty in terms of fitness may be more than compensated for by increased earlier survival (14). A life-history analysis assessing the evolutionary relevance of this hypothesis by elucidating the link between energy acquisition, risk reduction, and somatic maintenance, which is also firmly linked to empirical data, has apparently not yet been articulated.Our assessment of the above hypothesis is based on a simple life-history model illustrated using cohort survivorship data from the same species, obtained both in a natural ecological setting and also in a properly designed protective environment. This allows comparison of different somatic maintenance strategies with regard to female lifetime reproductive success and the intrinsic rate of natural increase, without invoking complex and specific population dynamics models that would narrow the empirical reach of predictions in terms of range of life-history regimes. The life-history model predicts that natural selection will, independent of temporal mortality risk profiles, favor restrained allocation to maintenance, despite causing accumulation of somatic damage in later life.After we present our model and results illustrating its relevance for three real-life case studies, we will examine its implications and relationships with the main current theories of evolution of aging (mutation accumulation, antagonistic pleiotropy, and disposable soma theory) (14). Our hypothesis is conceptually closest to the disposable soma theory. In essence, the disposable soma theory proposes that natural selection should favor allocation to somatic maintenance only as much as is necessary to keep the organism in good functional condition for as long as it has a reasonable chance still to be alive, subject to the prevailing level of risk. Within this viewpoint, it is commonly suggested to be optimal to allocate surplus resources in other activities that enhance fitness, thereby predicting trade-offs between, for example, longevity and reproduction. In our model, however, the emphasis is specifically on how restraining the allocation to maintenance increases fitness in early and middle life by lessening the mortality risk as such, without being traded against any other trait before late in life. If the predicted intimate link between risk reduction and somatic maintenance can be established through further theoretical and experimental work, we anticipate that it will advance our understanding of the evolutionary basis of aging and of the nature of any trade-offs that might arise. We also expect that enhanced understanding of why aging occurs may contribute fresh insights to guide research on physiological causes of and possible interventions to improve the aging process, a matter of high biomedical importance.     

Epidemiology of erectile dysfunction

Following the landmark Massachusetts Male Aging Study (MMAS) that provided the first relatively unbiased study of the epidemiology of erectile dysfunction (ED), a number of additional studies were carried out in the U.S. and around the world. The studies vary in quality because they used different definitions of ED, different assessment instruments, different and sometimes biased sources of populations, inadequate response rates to questionnaires and interviews, cultural disparities in willingness to discuss sexual issues, and differing interpretations of the results. Nevertheless, the studies demonstrated similar levels of ED by age and an exponential rise with age. They also generally confirmed the conditions that correlated with ED in the MMAS, namely, diabetes, hypertension, coronary artery disease, prostate cancer therapy, and depression. These were exacerbated by cigaret smoking.     

Age-dependent changes of K-elastin stimulated effector functions of human phagocytic cells: Relevance for atherogenesis

Effector functions of the elastin receptor on human phagocytic cells from young and older individuals were studied. In cells of young healthy subjects the elastin peptides, the agonists of receptor, stimulated both superoxide anion release from PMNs and phagocytosis of coated human red cells by monocytes. Elastin appeared to inhibit the cholesterol synthesis in monocytes, measured by the incorporation of ¹⁴C-acetate. In comparison with phagocytic cells of young (≤25 ± 6 years) subjects, PMNs of elderly donors (≥75 ±10 years) bore a similar number of binding sites for soluble elastin peptides, and the affinity of the elastin receptor was unchanged as shown by Scatchard analysis. The phagocytosis of coated human red cells stimulated by elastin peptides was also similar in the two age groups. However, several differences were found between phagocytic cells of young and elderly donors 1) PMNs of elderly released increased amounts of elastase from both resting and elastin peptide stimulated cells, and 2) monocytes of elderly showed a lack of inhibition of cholesterol synthesis by elastin peptides when maintained in cholesterol-free medium. These changes in effector functions of phagocytic cells from elderly donors might contribute to the age-dependent increase of susceptibility to the development of atherosclerotic lesions.     

Changes in cognitive function associated with sleep disordered breathing in older people

OBJECTIVES: Sleep disordered breathing (SDB) is very common in older people and is known to be associated with complaints of impaired daily functioning, including excessive daytime sleepiness and cognitive impairments. As part of a larger study on SDB and aging, it became possible to examine the relationship between SDB and cognition in older men and women. DESIGN: A population-based longitudinal study. SETTING: In-home interviews and home sleep recordings in the greater San Diego area. PARTICIPANTS: Community-dwelling people age 65 and older with high risk for SDB were originally studied from 1981 through 1985 and then followed every 2 years. Data from the 46 subjects who completed Visit 3 and Visit 4 are presented. MEASUREMENTS: Subjects were interviewed in the home about their sleep and medical condition before each visit. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Daytime sleepiness was based on self-report. Objective sleep was recorded in the home and scored for sleep, apneas and hypopneas, and oximetry variables. RESULTS: Increases in respiratory disturbance index (RDI) (P= .036) and increases in daytime sleepiness (P= .002) were associated with decreases in cognitive performance (i.e., increases in cognitive impairment). Increases in RDI were also associated with increases in daytime sleepiness (P= .012). Change in MMSE scores was therefore regressed onto changes in RDI, daytime sleepiness, age, and education, resulting in decreases in MMSE scores being associated with increases in daytime sleepiness (P= .019) but not with changes in RDI (P= .515). There was no significant relationship between changes in oxygen saturation levels and changes in MMSE. CONCLUSIONS: The results of this study suggest that declining cognitive function is associated primarily with increases in daytime sleepiness. Although cognitive decline was also associated with increases in RDI, this association did not hold in the more inclusive model which also included variable of SDB, oximetry, sleep and subjective report. One theoretical model could suggest that any relationship between SDB and cognitive function may be mediated by the effect of SDB on daytime sleepiness. These results suggest that older patients suffering from mild to moderate SDB may benefit from the treatment of SDB, even if they are not markedly hypoxemic.     

Continuous subcutaneous insulin infusion: A long-term study

Summary The authors report data obtained from a 3-year study of CSII and humanized insulin (semi-synthetic human insulin) administered to 18 insulin-dependent subjects in the outpatient clinic. The aim of this study was to evaluate the validity of insulin pumps in long-term treatment. Metabolic parameters were significantly improved (p<0.001) in the first month and remained so with only slight alterations throughout treatment. The authors underline some metabolic problems (ketosis) caused by malfunctioning of the insulin pumps, by the difficulties with the infusion sytem or by nodular skin lesions at the infusion site. Only these lesions called for treatment to be discontinued in 4 patients. The highest incidence of nodular skin lesions was seen after one year’s uninterrupted treatment and they seem connected to the duration of treatment rather than to the patients’ negligence (inadequate hygiene, delayed needle substitution). The authors conclude that CSII treatment is valid over short-term periods, whereas it presents drawbacks over long-term administration.     

Primary cutaneous mucormycosis in a lung transplant recipient: case report and concise review of the literature

Abstract: Mucormycosis (zygomycosis) is an invasive, opportunistic fungal infection caused by organisms of the class Zygomycetes. Immunocompromised individuals, including both solid organ and hematopoietic stem cell transplant recipients, are preferentially affected. Among solid organ transplant (SOT) recipients, the sinuses, with or without involvement of the orbits and cerebrum, are the most common sites of disease, although the pulmonary allograft appears to be targeted following lung transplantation. Here, we describe the unique case of a lung transplant recipient who developed multifocal cutaneous mucormycosis without involvement of the pulmonary allograft, and review the published literature regarding incidence, treatment, and prognosis of primary cutaneous mucormycosis following SOT.     

Obesity increases the risk of development of atherosclerosis in elderly type 2 diabetic patients*

Background: Obesity has been suggested to have no effect on the rates of mortality from cerebro‐ and cardiovascular diseases in the elderly. The purpose of the present study was to determine whether obesity influences atherosclerotic risk factors in elderly diabetic patients. Methods: The relationships between body mass index (BMI) and representative atherosclerotic risk factors were investigated using data from patients with type 2 diabetes who were aged from 65 to 91 years (mean ± standard deviation, 72.3 ± 5.2 years). Results: BMI significantly correlated with systolic and diastolic arterial pressures and serum triglyceride, uric acid and sialic acid levels. BMI also showed significant negative correlations with duration of diabetes and serum HDL cholesterol levels. Multiple regression analysis using BMI as a target variable and age, sex, duration of diabetes, mean arterial pressure, serum uric acid and triglyceride as explanatory variables showed that BMI significantly correlated with arterial pressure and serum triglyceride level (R = 0.459). After adjustment for history of drug therapy for each disease (hypertension, dyslipidemia or hyperuricemia), BMI also significantly correlated with arterial pressure, serum triglyceride, HDL cholesterol and uric acid levels. In the subjects with BMI of 25 or over, the mean levels of systolic and diastolic arterial pressures, serum triglyceride and sialic acid were higher and the mean level of serum HDL cholesterol was lower, after adjustment for age and sex, than those in the subjects with BMI below 22. Conclusion: These results suggest that obesity is related to arterial pressure, blood lipid and uric acid levels and increases the risk of development of atheroclerosis in elderly diabetic patients.     

ABC-ELISA检测血清粉尘螨特异性IgE

目的　应用ABC -ELISA法检测粉尘螨特异性IgE。 方法　按常规ABC -ELISA法操作 ,以阳性血清光密度值1 0时所需要的条件为最适条件 ,经预实验选择最适抗原包被浓度、血清稀释度和酶结合物浓度 ,并经特异性抑制试验验证。用ABC -ELISA法对 76例哮喘患者和 30例正常人进行粉尘螨特异性IgE检测 ,并与皮肤挑刺试验结果比较。 结果　ABC -ELISA法检测粉尘螨特异性IgE最适抗原包被浓度为 10 μg/ml,血清稀释倍数为 1∶4 0 ,Avidin -HRP为 1∶6 0 0 ,粉尘螨浸液和鼠抗人IgE均能抑制阳性反应。支气管哮喘患者和正常人粉尘螨特异性IgE校正OD值分别为 2 4 1± 1 13和 1 2 5± 0 5 6 ,差异具显著性 (χ2 =5 36 ,P <0 0 1)。粉尘螨浸液皮试与螨特异性IgE测定的符合率为 93 4 0 % (99/10 6 )。 结论　ABC -ELISA法检测粉尘螨特异性IgE耗时短 ,且具有较好的抗原特异性 ,建议临床推广应用。     

Coimpairments as predictors of severe walking disability in older women

OBJECTIVE: Severe disabilities are common among older people who have impairments in a range of physiologic systems. It is not known, however, whether the presence of multiple impairments, or coimpairments, is associated with increased risk of developing new disability. The aim of this study was to determine the combined effects of two impairments, decreased knee-extension strength and poor standing balance, on the risk of developing severe walking disability among older, moderately-to-severely disabled women who did not have severe walking disability at baseline. DESIGN: The Women's Health and Aging Study is a 3-year prospective study with 6 semi-annual follow-up data-collection rounds following the baseline. SETTING: At baseline, knee-extension strength and standing balance tests took place in the participants' homes. PARTICIPANTS: 758 women who were not severely walking disabled at baseline. MEASUREMENTS: Severe walking disability was defined as customary walking speed of < 0.4 meters/second and inability to walk one quarter of a mile, or being unable to walk. RESULTS: Over the course of the study, 173 women became severely disabled in walking. The cumulative incidence of severe walking disability from the first to the sixth follow-up was: 7.8%, 12.0%, 15.1% 19.5% 21.2%, and 22.8%. In Cox proportional hazards models, both strength and balance were significant predictors of new walking disability. In the best balance category, the rates of developing severe walking disability expressed per 100 person years were 3.1, 6.1, and 5.3 in the highest- to lowest-strength tertiles. In the middle balance category, the rates were 9.6, 13.2, and 14.7, and in the poorest balance category 21.6, 12.7, and 37.1, correspondingly. The relative risk (RR) of onset of severe walking disability adjusted for age, height, weight, and race was more than five times greater in the group with poorest balance and strength (RR 5.12, 95% confidence limit [95% CI] 2.68-9.80) compared with the group with best balance and strength (the reference group). Among those who had poorest balance and best strength, the RR of severe walking disability was 3.08 (95% CI 1.33-7.14). Among those with best balance and poorest strength, the RR was 0.97 (95% CI 0.49-1.93), as compared with the reference group. CONCLUSION: The presence of coimpairments is a powerful predictor of new, severe walking disability, an underlying cause of dependence in older people. Substantial reduction in the risk of walking disability could be achieved even if interventions were successful in correcting only one of the impairments because a deficit in only one physiologic system may be compensated for by good capacity in another system.