Allostatic load as a marker of cumulative biological risk: MacArthur studies of successful aging

Allostatic load (AL) has been proposed as a new conceptualization of cumulative biological burden exacted on the body through attempts to adapt to life's demands. Using a multisystem summary measure of AL, we evaluated its capacity to predict four categories of health outcomes, 7 years after a baseline survey of 1,189 men and women age 70-79. Higher baseline AL scores were associated with significantly increased risk for 7-year mortality as well as declines in cognitive and physical functioning and were marginally associated with incident cardiovascular disease events, independent of standard socio-demographic characteristics and baseline health status. The summary AL measure was based on 10 parameters of biological functioning, four of which are primary mediators in the cascade from perceived challenges to downstream health outcomes. Six of the components are secondary mediators reflecting primarily components of the metabolic syndrome (syndrome X). AL was a better predictor of mortality and decline in physical functioning than either the syndrome X or primary mediator components alone. The findings support the concept of AL as a measure of cumulative biological burden.     

Increases in serum non-high-density lipoprotein cholesterol may be beneficial in some high-functioning older adults: MacArthur studies of successful aging

objectives: To examine the association between changes in serum non-high-density lipoprotein cholesterol (non-HDL-C) over a 2.5-year period and risk of adverse health outcomes in the following 4.5 years in high-functioning older adults. DESIGN: Prospective cohort, established in 1988, with a follow-up in 1991 and 1995. SETTING: Population-based, community-dwelling men and women. PARTICIPANTS: A random sample (n=267) from the MacArthur cohort (N=1,189). The cohort represented the highest-functioning tertile of 4,030 screened candidates aged 70 to 79. MEASUREMENTS: Change in non-HDL-C between 1988 and 1991 was measured as a predictor of health outcomes between 1991 and 1995, including all-cause mortality, and among survivors, incident heart attack or stroke, development of new disability in basic activities of daily living, and decline in performance on the Short Portable Mental Status Questionnaire. RESULTS: More-positive change in non-HDL-C between 1988 and 1991 was associated with fewer adverse outcomes between 1991 and 1995. In individuals whose total cholesterol at baseline was in the middle two quartiles (195-244 mg/dL), each 10-mg/dL increase in the 1988-to-1991 change in non-HDL-C was associated with an adjusted mortality odds ratio (OR) of 0.67 (95% confidence interval (CI)=0.51-0.88). In individuals without cardiovascular disease at baseline, the adjusted OR for new physical disability was 0.79 (95% CI=0.65-0.95) and for cognitive decline was 0.81 (95% CI=0.67-0.98). CONCLUSION: Increases in cholesterol over time have beneficial associations in some older adults. The role of cholesterol changes in the health of older individuals needs further exploration.     

Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons: MacArthur studies of successful aging

BACKGROUND: Chronic inflammation has been proposed as a biological mechanism underlying the decline in physical function that occurs with aging. The purpose of this investigation was to examine the cross-sectional and prospective relationships between markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), with several measures of physical performance in older persons aged 70 to 79 years. METHODS: Subjects were 880 high-functioning men and women participating in the MacArthur Study of Successful Aging (n = 1189), a subset of the Established Populations for Epidemiologic Studies of the Elderly (n = 4030). Plasma IL-6 and CRP levels were determined by enzyme-linked immunosorbent assay and log transformed to normalize the distributions. Physical function measures included handgrip strength, signature time, chair stands (time to complete five repetitions), and 6-m walk time. RESULTS: Women had lower (p < .05) IL-6 levels than men, but there was no significant difference between blacks and whites. IL-6 and CRP levels were higher (p < .05) in current smokers than in nonsmokers and in those with a greater body mass index (BMI). Hours per year undertaking moderate and strenuous physical activity were also related to inflammatory markers with higher (p < .001) IL-6 and CRP levels in less active individuals. After adjusting for age, sex, race, BMI, smoking status, use of nonsteroidal anti-inflammatory drugs, and prevalence of morbidity, those in the top two quartiles for walking speed had lower (p = .012) IL-6 levels than those in the bottom quartile. In addition, there was a trend (p = .038) for lower CRP levels in those with higher walking speed. CRP levels were also lower (p = .04) in individuals in the top quartile for grip strength. No significant differences were noted for chair stands or signature time performance. Repeat performance measures obtained on 405 subjects (67% of those eligible at baseline) obtained 7 years later had declined significantly (grip strength, 18%; signature time, 21%; walking speed, 31%; p < .001), except for the chair rise; however, baseline IL-6 and CRP were not associated with a change in performance. However, those who died or who were unable to undergo testing had higher baseline IL-6 and CRP levels (p < .01) and slower walking speed (p < .05). CONCLUSIONS: Although IL-6 has been shown to predict onset of disability in older persons and both IL-6 and CRP are associated with mortality risk, these markers of inflammation have only limited associations with physical performance, except for walking measures and grip strength at baseline, and do not predict change in performance 7 years later in a high-functioning subset of older adults.     

The effects of serum beta-carotene concentration and burden of inflammation on all-cause mortality risk in high-functioning older persons: MacArthur studies of successful aging

BACKGROUND: It remains unclear to what extent the associations between low serum beta-carotene concentration and increased risk for cardiovascular disease and cancers are attributable to inflammation. The objective of this study was to evaluate simultaneously the effects of serum beta-carotene concentration and inflammation on the subsequent all-cause mortality risk in high-functioning older persons. METHODS: The authors conducted a prospective cohort study using information from 672 participants from the MacArthur Studies of Successful Aging. Baseline information was obtained for serum concentrations of beta-carotene, C-reactive protein, interleukin-6, cholesterols, and albumin; body mass index; waist:hip ratio; prevalent medical conditions; health behaviors; and medications. Sex-specific univariate and multivariate logistic regression analyses were used to study the effects of low beta-carotene, high inflammation burden, or both on 7-year all-cause mortality rates while adjusting for other confounders. RESULTS: The serum beta-carotene concentration was inversely associated with C-reactive protein and interleukin-6 levels. After adjustment for inflammation markers and other covariates, the relative risks for low beta-carotene for the 7-year all-cause mortality risk were 2.30 (95% confidence interval [CI], 1.23 to 4.31) in men and 0.85 (95% CI, 0.42 to 1.75) in women. Compared with men with high beta-carotene levels and low inflammation, the multiply adjusted relative risk for low beta-carotene and high inflammation burden was 3.78 (95% CI, 1.69 to 8.47) in men. CONCLUSIONS: Low levels of serum beta-carotene are independently associated with an increased all-cause mortality risk in older men, even after adjustment for the effects of inflammation and other risk factors. In men, but not women, a synergistic effect occurs between low beta-carotene concentration and high inflammation burden in predicting higher mortality rates.     

Association between serum beta-carotene levels and decline of cognitive function in high-functioning older persons with or without apolipoprotein E 4 alleles: MacArthur studies of successful aging

BACKGROUND: Growing evidence from animal studies suggests an interaction between antioxidants and apolipoprotein E (APOE) alleles on cognitive functioning. We used data from a 7-year cohort study of high-functioning older persons to explore whether the associations between serum beta-carotene level and subsequent decline of cognitive function differed by APOE 4 genotype. METHODS: Baseline information on sociodemographic characteristics, serum beta-carotene level, inflammation markers, APOE genotype, and cognitive functioning measured by a 9-item Short Portable Mental Status Questionnaire (SPMSQ) was obtained in 455 survivors. Multivariable logistic regression analyses were used to examine the relation between high serum beta-carotene level and risk of SPMSQ score decline in participants with or without APOE 4 alleles, while adjusting for age, sex, race, baseline SPMSQ score, and other covariates. RESULTS: Nine (2%) study participants had homozygous and 97 (21%) had heterozygous APOE 4 alleles. Two hundred forty-nine (55%) had decline of SPMSQ scores during the follow-up. The presence of an APOE 4 allele was associated with higher risk and larger magnitude of SPMSQ score decline. The adjusted odds ratio of high beta-carotene level for cognitive decline was 0.11 (95% confidence interval, 0.02-0.57) in participants with at least one APOE 4 allele and 0.89 (95% confidence interval, 0.54-1.47) among those who were APOE 4 negative. CONCLUSION: Among high-functioning older persons, antioxidants and beta-carotene in particular may offer protection from cognitive decline in persons with greater genetic susceptibility as evidenced by the presence of the APOE 4 allele.     

Self-efficacy as a mediator between fear of falling and functional ability in the elderly

OBJECTIVES: This study examined falls self-efficacy and fear of falling to determine whether self-efficacy acts as a mediator between fear of falling and functional ability. METHODS. Using the Survey of Activities and Fear of Falling in the Elderly as a fear-of-falling measure and the Activities-Specific Balance Confidence Scale for falls self-efficacy, structural relationships among fear of falling, self-efficacy, functional balance, and physical functioning outcomes were tested with older adults (N = 256, M age = 77.5). RESULTS. Lower levels of fear of falling were significantly related to higher levels of falls self-efficacy, which was in turn associated with better functional outcomes. Moreover, falls self-efficacy mediated the effects of fear of falling on functional outcomes. DISCUSSION. Results substantiate the hypothesized mediational role of falls self-efficacy in fear of falling and underscore the need to consider ways of enhancing falls self-efficacy in interventions aimed at reducing falls and fear of falling.     

Self-efficacy beliefs as predictors of loneliness and psychological distress in older adults

Sociodemographic variables, social support, and physical health have been used previously in a few predictor models of loneliness and psychological distress in late life. The present study, however, was designed to test the hypothesis that self-efficacy beliefs of elderly persons are significantly stronger predictors of loneliness and psychological distress than are demographics, social support, and physical health variables used in earlier predictor models. A sample of 141 women and 101 men, aged 65 to 86, reporting awide range of health status from "poor" to "excellent" was drawn from the region of Southern Alberta. Standard self-report measures were used to assess perceived self-efficacy in eight different domains. Findings from a series of hierarchical regression analyses that were conducted separately for men, women, and the combined sample supported the hypothesis concerning the superiority of the self-efficacy variables as predictors of loneliness and psychological distress. Gender-specific variations revealed that women's stronger self-efficacy domains in the interpersonal, social, and emotional realms, and men's stronger self-efficacy beliefs in the instrumental, financial, and physical realms predicted less loneliness and psychological distress. Spiritual self-efficacy emerged as being the most potent predictor, accounting for the largest percentage of explained variance in loneliness and psychological distress in the women's and combined sample. Implications of the findings are discussed for geriatric practitioners and clinicians.     

Hypercoagulability in centenarians: the paradox of successful aging

With advancing age, an increasing number of healthy individuals have laboratory signs of heightened coagulation enzyme activity. Such biochemical hypercoagulability might be the basis of either the increased thrombotic tendency occurring with age or a harmless manifestation of this process. To see whether these alterations are also present in the very elderly who had aged successfully, 25 healthy centenarians were studied and results of coagulation and fibrinolysis measurements were compared with those obtained in two control groups of healthy adults, 25 ranging in age from 18 to 50 years and 25 from 51 to 69 years. Older controls had, in general, slightly higher values of several coagulation and fibrinolysis measurements than younger controls. Centenarians had striking signs of heightened coagulation enzyme activity, as assessed directly by measuring activated factor VII in plasma (P < .01, compared with either control group) or indirectly by measuring the plasma levels of the activation peptides of prothrombin, factor IX, factor X, and thrombin-antithrombin complexes (all P < .001). Heightened coagulation enzyme activity was accompanied by signs of enhanced formation of fibrin (high fibrinopeptide A, P < .001) and secondary hyperfibrinolysis (high D-dimer and plasmin- antiplasmin complex, P < .001). Plasma concentrations of fibrinogen and factor VIII were higher than in controls, whereas other coagulation factors were not elevated. In conclusion, this study shows the very elderly do not escape the state of hypercoagulability associated with aging, but that this phenomenon is compatible with health and longevity. Hence, high plasma levels of the coagulation activation markers in older populations do not necessarily mirror a high risk of arterial or venous thrombosis.     

Determinants of successful aging in Switzerland

The research, upon which this article is based is part of a program on "Social Integration" sponsored by the Swiss National Science Foundation. A sample of 4500 persons aged more than 59 years were interviewed in 1978. The theoretical approach was to identify the elements of successful aging under the conditions of swiss society, which are: the quality and degrees of independence and self determination of personality, continuity of the manner of living and adequate handling of the changing conditions of life in the third age including physical, mental, communicational and economic mutations. To reach this goal the survey measured the socio-economic conditions of the investigated population, their psycho-physical ability, how old people compensate deficits: the conditions essential for life, integration in leisure, private contacts, public opinions and political participation. The results show that a great majority is satisfied with the conditions of dwelling, occupation and economic conditions. But in all dimensions of life we also found minorities oppressed, threatened or deprived. Psycho-physical fitness proved to be in good state for a great majority and only a few percent were in a physical or mental condition which did not grant them independence and self-determination. This diagnosis was assisted by the results of two newly developed tests for meaning ability.     

Hypothalamic secretion of thyrotropin releasing hormone declines in aging rats

Young and aged male rats were used in experiments to investigate a possible decline in hypothalamic secretion of thyrotropin releasing hormone (TRH) to the anterior pituitary of aging mammals. We observed a 66% decrease in basal TRH release by incubated rat hypothalami with aging. Thyroid hormone-responsive hepatic alpha-glycerophosphate dehydrogenase (GPD) and malic enzyme (ME) levels in aged rats did not differ from 5-month-old controls in spite of a significant fall in serum thyroxine (T4) levels with aging. Other results suggest that these particular indicators of thyroidal status should not change in the aging rat because serum T3 is maintained in the normal range. Serum thyrotropin (TSH) levels, which normally rise when serum T4 levels decline, did not change with aging. These data suggest that gradual loss of the essential TRH stimulation of TSH release with aging may be compensated for by a decline in T4 inhibition of TSH release at the pituitary.     

Self-efficacy, social support, and depression in aging: a longitudinal analysis

This study examines the relationship of self-efficacy and social support to adjustment in aging. Fifty-two community residents participated in an initial structured interview and a follow-up interview one year later. Measures of depression and self-efficacy relating to social support were included in the initial interview, with measures of depression and actual social support included at follow-up. Results showed that initial self-efficacy was related to social support one year later. A path analysis showed that self-efficacy functions directly as well as indirectly through its effect on social support in preventing depression. A partial correlational analysis showed that the relationships between initial self-efficacy and depression one year later and between social support and depression at follow-up hold when ongoing depression is controlled.     

Self-perception of aging and perceived medical discrimination

Background

Individuals who perceive medical discrimination often face adverse consequences. How individuals perceive their own aging experiences may influence perceived medical discrimination due to age by generating expectations that they will receive poor treatment from clinicians, which may be amplified for individuals who also perceive discrimination because of race. This study explored the relationship between self-perceptions of aging (SPA) and perceived medical discrimination due to age, race, and other reasons.

Methods

We used three waves (2008, 2012, 2016) from the nationally representative Health and Retirement Study (HRS) data. Our sample included 10,188 community-residing individuals aged 51 and over. SPA were measured by two domains: positive SPA and negative SPA. Multinomial logistic regression that adjusted for demographic, health characteristics, and year-fixed effects was conducted to estimate the relationship between SPA and categories of perceived medical discrimination (age, race, age and race, and other).

Results

Approximately 11% of the population perceived discrimination because of age or race in the medical setting from 2008 to 2016. Older adults who had a positive SPA were 15% [Adjusted relative risk ratio (ARR): 0.85, 95% CI: 0.79–0.91], 13% [ARRR: 0.87, 95% CI: 0.76–1.00], and 20% [ARRR: 0.80, 95% CI: 0.74–0.88] less likely to experience perceived medical discrimination due to age, race, and the intersection of age and race, respectively, than those who did not, holding other factors constant. Those who held a negative SPA were 38% [ARRR: 1.38, 95% CI: 1.28–1.48] more likely to report perceived medical discrimination due to age and 12% [ARRR: 1.12, 95% CI: 1.03–1.21] more likely to report perceived medical discrimination due to other reasons.

Conclusions

Holding a positive perception of aging may help reduce perceived medical discrimination because of age and race, which may in turn improve communication and lead to timely and appropriate treatment.     

Genes and environment in successful and unsuccessful aging

Only about one quarter of human longevity is heritable; the rest of the variance is attributable to environment and to stochastic events. The environment includes 'segmental gerontogens' (e.g. tobacco smoke) that affect multiple senescent phenotypes, as well as 'unimodal gerontogens' (e.g. UV) that affect aging of a single tissue. Research on both 'gerontogens' and 'gerontogenes' will help us understand the differences between successful and unsuccessful human aging.
Nature fails to eliminate gene variants with bad late life actions and also fails to select novel alleles with good late life actions. A classification of such gene actions predicts roles for numerous genes. ^1,2 But there is evidence that single gene mutations and a single environmental manipulation (caloric restriction) can enhance longevity. These interventions impact upon ancient genetic programs ('diapauses') that couple environmental changes that threaten reproductive success with transient withdrawals from reproduction. Such a 'reprieve' ('shikko-yuyo'), however, cannot escape the dominating mechanisms predicted by the evolutionary theory of aging which, despite recent challenges, still provides the best explanation for why we age. The identification of multiple genes and environmental agents, both good and bad, that contribute to successful or unsuccessful aging in various settings should help elucidate basic mechanisms of biological aging.     

Sustained personal autonomy: a measure of successful aging

OBJECTIVES. This study addresses the following question: What characteristics of urban, noninstitutionalized elders predict which individuals are most likely to remain independent of personal assistance during a 2-year observation period? METHODS. A population-based sample of 602 noninstitutionalized urban residents aged 70 and older was followed for 2 years. RESULTS. Ninety-eight of the 487 survivors remained independent. Factors associated with sustained independence were relatively younger age, male gender, fewer medical conditions, good physical function, and nonsmoking. The attitudes "favors family or self over agency assistance" and "does not expect filial obligation" were also independently associated. DISCUSSION. The results are consistent with previous studies of successful aging and show that attitudes expressed at baseline favoring personal independence are associated with sustained autonomy during a period of at least 2 years.     

Psychological principles of successful aging technologies: a mini-review

Based on resource-oriented conceptions of successful lifespan development, we propose three principles for evaluating assistive technology: (a) net resource release; (b) person specificity, and (c) proximal versus distal frames of evaluation. We discuss how these general principles can aid the design and evaluation of assistive technology in adulthood and old age, and propose two technological strategies, one targeting sensorimotor and the other cognitive functioning. The sensorimotor strategy aims at releasing cognitive resources such as attention and working memory by reducing the cognitive demands of sensory or sensorimotor aspects of performance. The cognitive strategy attempts to provide adaptive and individualized cuing structures orienting the individual in time and space by providing prompts that connect properties of the environment to the individual's action goals. We argue that intelligent assistive technology continuously adjusts the balance between 'environmental support' and 'self-initiated processing' in person-specific and aging-sensitive ways, leading to enhanced allocation of cognitive resources. Furthermore, intelligent assistive technology may foster the generation of formerly latent cognitive resources by activating developmental reserves (plasticity). We conclude that 'lifespan technology', if co-constructed by behavioral scientists, engineers, and aging individuals, offers great promise for improving both the transition from middle adulthood to old age and the degree of autonomy in old age in present and future generations.     

Exercise and hormesis: oxidative stress-related adaptation for successful aging

The hormesis theory purports that biological systems respond with a bell-shaped curve to exposure to chemicals, toxins, and radiation. Here we extend the hormesis theory to include reactive oxygen species (ROS). We further suggest that the beneficial effects of regular exercise are partly based on the ROS generating capability of exercise, which is in the stimulation range of ROS production. Therefore, we suggest that exercise-induced ROS production plays a role in the induction of antioxidants, DNA repair and protein degrading enzymes, resulting in decreases in the incidence of oxidative stress-related diseases and retardation of the aging process.