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Five healthy aging phenotypes were developed in the Long Life Family Study to uncover longevity pathways and determine if healthy aging across multiple systems clustered in a subset of long-lived families. Using blood pressure, memory, pulmonary function, grip strength, and metabolic measures (body mass index, waist circumference and fasting levels of glucose, insulin, triglycerides, lipids, and inflammatory markers), offspring were ranked according to relative health using gender-, age-, and relevant confounder-adjusted z-scores. Based on our prior work, families met a healthy aging phenotype if ≥ 2 and ≥ 50% of their offspring were exceptionally healthy for that respective phenotype. Among 426 families, only two families met criteria for three healthy aging phenotypes and none met criteria for four or more healthy aging phenotypes. Using Spearman correlation, the proportion of offspring within families with exceptionally healthy pulmonary function was correlated with the proportion of offspring within families with exceptional strength (r = 0.19, p = 0.002). The proportion of offspring within families meeting the healthy blood pressure and metabolic phenotypes were also correlated (r = 0.14, p = 0.006), and more families were classified as meeting healthy blood pressure and metabolic phenotypes (Kappa = 0.10, p = 0.02), as well as the healthy pulmonary and blood pressure phenotypes than expected by chance (Kappa = 0.09, p = 0.03). Other phenotypes were weakly correlated (|r| ≤ 0.07) with low pairwise agreement (Kappa ≤ 0.06). Among these families selected for familial longevity, correspondence between healthy aging phenotypes was weak, supporting the heterogeneous nature of longevity and suggesting biological underpinnings of each individual phenotype should be examined separately to determine their shared and unique determinants.

One method by which to identify fundamental biological processes that may contribute to age-related disease and disability, instead of disease-specific processes, is to construct endophenotypes comprising linear combinations of physiological measures. Applying factor analyses methods to phenotypic data (2006-2009) on 28 traits representing 5 domains (cognitive, cardiovascular, metabolic, physical, and pulmonary) from 4,472 US and Danish individuals in 574 pedigrees from the Long Life Family Study (United States and Denmark), we constructed endophenotypes and assessed their relationship with mortality. The most dominant endophenotype primarily reflected the physical activity and pulmonary domains, was heritable, was significantly associated with mortality, and attenuated the association of age with mortality by 24.1%. Using data (1997-1998) on 1,794 Health, Aging and Body Composition Study participants from Memphis, Tennessee, and Pittsburgh, Pennsylvania, we obtained strikingly similar endophenotypes and relationships to mortality. We also reproduced the endophenotype constructs, especially the dominant physical activity and pulmonary endophenotype, within demographic subpopulations of these 2 cohorts. Thus, this endophenotype construct may represent an underlying phenotype related to aging. Additional genetic studies of this endophenotype may help identify genetic variants or networks that contribute to the aging process., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study investigated the association between maternal age at birth of last child and likelihood of survival to advanced age., Methods: This was a nested case-control study using Long Life Family Study data. Three hundred eleven women who survived past the oldest 5th percentile of survival (according to birth cohort-matched life tables) were identified as cases, and 151 women who died at ages younger than the top 5th percentile of survival were identified as controls. A Bayesian mixed-effect logistic regression model was used to estimate the association between maternal age at birth of last child and exceptional longevity among these 462 women., Results: We found a significant association for older maternal age, whereby women who had their last child beyond age 33 years had twice the odds for survival to the top 5th percentile of survival for their birth cohorts compared with women who had their last child by age 29 years (age between 33 and 37 y: odds ratio, 2.08; 95% CI, 1.13 to 3.92; older age: odds ratio, 1.92; 95% CI, 1.03 to 3.68)., Conclusions: This study supports findings from other studies demonstrating a positive association between older maternal age and greater odds for surviving to an unusually old age.