Biomedical subjects

Bradley J Willcox

Publications and source records attributed to Bradley J Willcox.

8 recordsLinked to original sources

PubMed2006

Midlife risk factors and healthy survival in men.

CONTEXT: Healthy survival has no clear phenotypic definition, and little is known about its attributes, particularly in men. OBJECTIVE: To test whether midlife biological, lifestyle, and sociodemographic risk factors are associated with overall survival and exceptional survival (free of a set of major diseases and impairments). DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study within the Honolulu Heart Program/Honolulu Asia Aging Study. A total of 5820 Japanese American middle-aged men (mean age, 54 [range, 45-68] years) free of morbidity and functional impairments were followed for up to 40 years (1965-2005) to assess overall and exceptional survival. Exceptional survival was defined as survival to a specified age (75, 80, 85, or 90 years) without incidence of 6 major chronic diseases and without physical and cognitive impairment. MAIN OUTCOME MEASURE: Overall survival and exceptional survival. RESULTS: Of 5820 original participants, 2451 participants (42%) survived to age 85 years and 655 participants (11%) met the criteria for exceptional survival to age 85 years. High grip strength and avoidance of overweight, hyperglycemia, hypertension, smoking, and excessive alcohol consumption were associated with both overall and exceptional survival. In addition, high education and avoidance of hypertriglyceridemia were associated with exceptional survival, and lack of a marital partner was associated with mortality before age 85 years. Risk factor models based on cumulative risk factors (survival risk score) suggest that the probability of survival to oldest age is as high as 69% with no risk factors and as low as 22% with 6 or more risk factors. The probability of exceptional survival to age 85 years was 55% with no risk factors but decreased to 9% with 6 or more risk factors. CONCLUSION: These data suggest that avoidance of certain risk factors in midlife is associated with the probability of a long and healthy life among men.

Aged↗

PubMed2006

Caloric restriction and human longevity: what can we learn from the Okinawans?

Caloric (or dietary) restriction (CR) extends lifespan and lowers risk for age associated diseases in a phylogenetically diverse group of species. Whether prolonged CR increases average or maximum lifespan or promotes a more youthful physiology in humans at advanced ages is not yet known. However, available epidemiological evidence indicates that CR may already have contributed to an extension of average and maximum life span in one human population and appears to have lowered risk for age associated chronic diseases in other human populations. We review the human studies in the context of a special human population, older Okinawans, who appear to have undergone a mild form of prolonged CR for about half their adult lives.

Aging↗

PubMed2006

Siblings of Okinawan centenarians share lifelong mortality advantages.

Okinawa, an isolated island prefecture of Japan, has among the highest prevalence of exceptionally long-lived individuals in the world; therefore, we hypothesized that, within this population, genes that confer a familial survival advantage might have clustered. We analyzed the pedigrees of 348 centenarian families with 1142 siblings and compared sibling survival with that of the 1890 Okinawan general population cohort. Both male and female centenarian siblings experienced approximately half the mortality of their birth cohort-matched counterparts. This mortality advantage was sustained and did not diminish with age in contrast to many environmentally based mortality gradients, such as education and income. Cumulative survival advantages for this centenarian sibling cohort increased over the life span such that female centenarian siblings had a 2.58-fold likelihood, and male siblings a 5.43-fold likelihood, versus their birth cohorts, of reaching the age of 90 years. These data support a significant familial component to exceptional human longevity.

Aged, 80 and over↗

PubMed2006

Disability and depression: investigating a complex relation using physical performance measures.

OBJECTIVE: The objective of this study was to examine the relation of physical performance measures with depressive symptoms in older men. METHOD: A cross-sectional, multivariate comparison of several measures of upper- and lower-extremity performance and their relation with depressive symptoms was performed in 2,856 older Japanese American men, aged 71-93 years, who participated in the fourth examination of the Honolulu Heart Program. Depressive symptoms were measured using an 11-item version of Center for Epidemiologic Studies Depression (CES-D) Scale. A score of at least 9 (from a maximum score of 33) is considered clinically significant. Timed functional performance tests, including walking and repeated chair stands, were used to assess lower-extremity performance; handgrip strength was used as an indicator of upper-extremity performance. RESULTS: Two hundred eighty-three participants (9.9%) had a score of 9 or greater on the 11-question CES-D Scale and were considered to be at high risk for depression. Time to walk 10 feet and time to complete five chair stands were significantly longer in those with depressive symptoms, whereas handgrip strength was significantly lower. Only the association of gait speed (time to walk 10 feet) and depressive symptoms remained significant when all physical performance measures were simultaneously included in a multivariate analysis. CONCLUSION: These results demonstrate physical performance measures, particularly gait speed, may be important potential correlates of depression in community-dwelling older men.

Aged↗

PubMed2004

Growth-associated proteins and regeneration-induced gene expression in the aging neuron.

Axonal elongation and sprouting during regeneration are retarded with aging but the etiology of this is unclear. We investigated whether this age-associated decline is related to a decline in expression of three different growth-associated proteins (GAPs): alpha(1)-tubulin, neurofilament (NF) light subunit (NF-L) and GAP-43. Northern analysis was performed on L4-L5 dorsal root ganglia (DRG) of young (3 months) and aged (23 months) rats following a sciatic nerve crush and compared to their age-matched controls. The results show that initial mRNA levels of alpha(1)-tubulin and NF-L in the control aged rat DRG were half those of the control young adults, whereas expression of GAP-43 was unchanged. Two weeks after axotomy, the expression of alpha(1)-tubulin and GAP-43 in the aged DRG was induced to the same levels as in the axotomized young adult, and the expression of NF-L decreased proportionately in both age groups. These results indicate that certain neuronal mRNAs, such as alpha(1)-tubulin and NF-L may be maintained at lower levels in aging DRG neurons, whereas others, such as GAP-43 appear to be unaltered. However, during regeneration, the aging DRG neuron appears capable of inducing alpha(1)-tubulin, NF-L and GAP-43 as well as the young adult.

Aging↗

PubMed2004

First autopsy study of an Okinawan centenarian: absence of many age-related diseases.

Consistent with the compression-of-morbidity hypothesis, several studies have reported that a significant proportion of centenarians delay or escape age-related diseases. Of those who live with such diseases for a long time, many appear to do so with better functional status than do younger persons who do not achieve extreme old age. The authors describe the first autopsy in an Okinawan-Japanese centenarian who escaped many age-related illnesses and delayed frailty toward the end of her very long life. Her late-life morbidity pattern is contrasted with that of white centenarians.

Aged↗

PubMed2004

How much should we eat? The association between energy intake and mortality in a 36-year follow-up study of Japanese-American men.

Energy restriction extends life span and lowers mortality from age-related diseases in many species, but the effects in humans are unknown. We prospectively examined this relationship in a large epidemiological study of Japanese-American men. We followed 1915 healthy nonsmokers, aged 45-68 years at study onset, for 36 years. Twenty-four-hour recall of diet was recorded at baseline, and follow-up was for all-cause mortality. After adjustment for age and other confounders, there was a trend toward lower mortality in the second quintile of energy intake, suggesting that men who consumed 15% below the group mean were at the lowest risk for all-cause mortality. Increased mortality was seen with intakes below 50% of group mean. Thus, we observed trends between low energy intake and reduced risk for all-cause mortality in humans until energy intake fell to less than half the group mean, consistent with previous findings in other species.

Aged↗

PubMed2004

C-reactive protein, cardiovascular disease and stroke: new roles for an old biomarker.

Stroke is a leading cause of death and disability worldwide. A new and exciting development in cardiovascular disease is the recognition of the role of inflammation in atherosclerosis. C-reactive protein, an acute phase reactant, appears to be a promising biomarker for cardiovascular disease, possibly more predictive than cholesterol and also may play an etiological role. C-reactive protein also appears to be predictive of stroke risk, although less so in the elderly. Although the number of studies on stroke (apart from cardiovascular disease) is limited, there is a significant graded increase in stroke risk within the low-to-high normal range of C-reactive protein. C-reactive protein is readily amenable to treatment with anti-inflammatory drugs, such as aspirin and statins. New and increasingly available high-sensitivity assays may make C-reactive protein a standard screening tool for cardiovascular disease.

Biomarkers↗