SummaryThe search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity.
The authors examined the effects of Hurricanes Katrina and Rita (HKR) on cognitive and psychosocial functioning in a lifespan sample of adults 6 to 14 months after the storms. Participants were recruited from the Louisiana Healthy Aging Study (LHAS). Most were assessed during the immediate impact period and retested for this study. Analyses of pre-and post-disaster cognitive data confirmed that storm-related decrements in working memory for middle-aged and older adults observed in the immediate impact period had returned to pre-hurricane levels in the post-disaster recovery period. Middle-aged adults reported more storm-related stressors and greater levels of stress than the two older groups at both waves of testing. These results are consistent with a burden perspective on post-disaster psychological reactions.
Diuretics use and overactive bladder syndrome are common in older adults. However, the relationship between the two has not been well studied. Data were collected by self-administered questionnaires including the Urge Urinary Distress Inventory (Urge-UDI) and the Urge Incontinence Impact Questionnaire (Urge-IIQ), and by outpatient chart abstraction. Patients (n = 172) had a mean age of 79 ± 7.5 (± S.D.), 76% were women, and 48% were African Americans; 76% had hypertension, 32% had heart failure, and 66% were receiving diuretics (57% loop diuretics). Overall, 72%, 68%, and 73% of patients respectively reported urinary frequency, urgency and urge incontinence. Diuretic use was associated with increased frequency (81% versus 55% non-diuretic; odds ratio = OR = 3.48; 95% confidence interval = CI = 1.73–7.03) and urgency (74% versus 57% non-diuretic; OR = 2.17; 95% CI = 1.11–4.24) but not with incontinence (OR = 1.74; 95% CI = 0.87–3.50). When adjusted for propensity scores, diuretic use had independent associations with frequency (adjusted OR = 3.09; 95% CI = 1.20–7.97) and urgency (adjusted OR = 2.50; 95% CI = 1.00–6.27). In addition to frequency and urgency, loop diuretic use was also associated with incontinence (OR = 2.54; 95% CI = 1.09–5.91), which lost significance after propensity adjustment (adjusted OR = 1.88; 95% CI = 0.57–6.17). Overall summary mean Urge-IIQ score was 1.83 ± 0.85 (±S.D.) with 1.75 ± 0.86, 1.68 ± 0.76, and 2.03 ± 0.88, respectively for no-diuretic, non-loop, and loop-diuretic patients (one-way ANOVA p = 0.063). Overactive bladder symptoms were common among ambulatory older adults and were associated with diuretic use, and had stronger associations with loop diuretic use.
We examined health-related quality of life in adults in the Louisiana Healthy Aging Study (LHAS) after Hurricanes Katrina and Rita that made landfall on the United States Gulf Coast region in 2005. Analyses of pre- and post-disaster SF-36 scores yielded declines in physical function and bodily pain. Mental health scores were lower for women than men. Gender differences were observed in religious beliefs and religious coping, favoring women. Religious beliefs and religious coping were negatively correlated with physical function, implying that stronger reliance on religiosity as a coping mechanism may be more likely among those who are less physically capable.
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