Measuring/Estimating Length by Quantitative Real-Time PCR. Genomic was extracted from blood samples and stored at −80°C. The average triplicate) telomere length in leukocytes was estimated using a PCR (qPCR) method (48). This approach provides relative average lengths in genomic DNA by determining the T/S ratio in experimental ples relative to a reference sample. Briefly, standard curves were for telomere lengths and for the single-gene copy amplification from a reference DNA sample that was serially diluted with water by 1.68-fold per dilution to produce 5 concentrations of DNA from 7.7 to 61 ng/μL. For analysis of subjects’ DNA, triplicate PCR

lotypes were constructed using the PHASE algorithm (50). The haplotype trend regression analysis for logistical (case-control), linear (telomere length), and proportional hazard with telomere length was performed using JMP genomics 4 (SAS Inc., Cary, NC).

parameter is set to 0 with the model in which the parameter is estimated. In addition, we compared telomere length between offspring and controls using a hierarchical linear regression model to account for clustering within families. The regression equation adjusted for age and gender included an indicator variable distinguishing offspring from controls and an offspring vs. controls × age interaction term. We tested the hypotheses that offspring have higher mean telomere length than controls and that the age-related decline in telomere length is less in offspring than in controls. To determine the effect of lipid profile on telomere length, a general linear model ad- justed for group, gender, and age at recruitment was used. Correlations of telomere length and lipid profile adjusted for group, gender, and age at recruitment were evaluated using Spearman rank correlation coefficients. Heritability of telomere length was assessed in two ways: First, it was com- puted in the ASSOC module of SAGE (v6.0.1) (http://darwin.cwru.edu/sage/). Second, narrow sense heritability was estimated from the slope of the linear regression of the traits of each parent on the mean value of the offspring group (16). Data are expressed as mean (SE) as appropriate. Statistical

ACKNOWLEDGMENTS. We are indebted to all participants and their families for their dedication and enthusiasm to enroll in the longevity study. We are also grateful to the Hebrew Home for the Aging (Riverdale, NY), Kittay House (Bronx, NY), Hebrew Home Hospital (West Hartford, CT), and Jewish Home for the Aged (New Haven, CT), all under the aegis of the association for the Jewish Aging Services (Washington, DC). This work was supported by grants from the Paul Beeson Physician Faculty Scholar in Aging Award, Ellison Medical Foundation Senior Scholar Award, Glenn Award for Research in Biological Mechanisms of Aging, and theResnick Gerontology Center, and by National Institutes of Health Grants RO1 AG- 18728-01A1, RO1 AG024391, PO1 AG027734, PO1 AG17242 and RO1 AG7992, General Clinical Research Center Grant MO1-RR12248, and Dia- betes Research and Training Center Grant DK 20541 at the Albert Einstein College of Medicine. Some of the results of this paper were obtained by using the program package S.A.G.E., which is supported by a U.S. Public Health Service Resource Grant (RR03655) from the National Center for Research Resources.

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