HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging.

The 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.

Depression and nursing home admission among hospitalized older adults with coronary artery disease: a propensity score analysis.

Admission to a nursing home is considered a poor outcome for community-dwelling older adults. The objective of this study was to determine whether depression increased the risk of nursing home admission. Using the National Hospital Discharge Survey 2001-2003 datasets, the authors identified 28,172 community-dwelling older adults, 65 years and older, discharged alive with a primary discharge diagnosis of coronary artery disease. The objective of this study was to determine the association between depression and subsequent nursing home admissions in these patients. Propensity scores for depression, calculated for each patient using a multivariable logistic regression model, were used to match 686 depressed patients with 2058 nondepressed patients who had similar propensity scores. Logistic regression analyses were used to determine the association between depression and nursing home admission. Patients had a mean age +/- SD of 77+/-8 years, and 61% were women. Compared with 9% of nondepressed patients, 13% of depressed patients were admitted to nursing homes (relative risk, 1.42; 95% confidence interval, 1.12-1.78). When adjusted for various demographic, clinical, and care-related covariates, the association became somewhat stronger (adjusted relative risk, 1.55; 95% confidence interval, 1.21-1.99). In ambulatory older adults hospitalized with coronary artery disease, a secondary diagnosis of depression was associated with a significantly increased risk of nursing home admission.

Geriatric heart failure, depression, and nursing home admission: an observational study using propensity score analysis.

OBJECTIVE: Heart failure (HF) and depression are both common in older adults, and the presence of depression is known to worsen HF outcomes. For community-dwelling older adults, admission to a nursing home (NH) is associated with loss of independent living and poor outcomes. The objective of this study was to examine the effect of depression on NH admission for older adults with HF. METHODS: Using the 2001-2003 National Hospital Discharge Survey datasets, the authors identified all community-dwelling older adults who were discharged alive with a primary discharge diagnosis of HF. The authors then identified those with a secondary diagnosis of depression. Using a multivariable logistic regression model, the authors then determined probability or propensity to have depression for each patient. The authors used propensity scores for depression to match all 680 depressed patients with 2,040 nondepressed patients. Finally, the authors estimated the association between depression and NH admission using bivariate and multivariable logistic regression analyses. RESULTS: Patients had a mean (+/- standard deviation) age of 79 (+/- 8) years, 72% were women, and 9% were blacks. Compared with 17% nondepressed patients, 25% depressed patients were discharged to a NH. Depression was associated with 50% increased risk of NH admission (unadjusted relative risk [RR]: 1.50; 95% confidence interval [CI]: 1.28-1.74). The association became somewhat stronger after multivariable adjustment for various demographic and care covariates (adjusted RR: 1.60; 95% CI: 1.35-1.68). CONCLUSION: In ambulatory older adults hospitalized with HF, a secondary diagnosis of depression was associated with a significant increased risk of NH admission.