Introduction 1986 1999 2001 2004 2006b 1998 2003 1987 1994 1995 1987 1995 1996 1997 1999 2002 1993 1999 2003 2003 2002 2004 1993 1996 2000 2002 2004 2005) 2004 The aim of our study was to investigate the extent and mode of inheritance of a skeletal biomarker of biological aging (OSS) in a large sample of ethnically homogeneous pedigrees. Materials and methods Sample The population sampled consisted of native Chuvashians residing in numerous small villages in the Chuvashia and Bashkartostan Autonomies of the Russian Federation. The data were gathered in three field studies during August/September of 1994 (555 individuals), May/June of 1999 (715 individuals), and September 2002 (240 individuals) by investigators from the Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University (Israel), and the Institute of Anthropology, Moscow University (Russia). The expeditions were part of a Chuvashia Skeletal Aging Study (ChuSAS) project whose main aim was to investigate the different aspects of skeletal aging within the Chuvashia population. All information collected and measurements taken during all expeditions were done by the same team of investigators. The investigated cohort comprised 359 families and included 787 men aged 18–89 years (mean 46.9) and 723 women aged 18–90 years (mean 48.5). 2003 2006 2006 2007 2007b Hand radiographs 1996 OSS evaluation 1995 1997 2005 2007b k P P 2007b 1 1986 Fig. 1 Mean OSS values and standard deviations (SD) in age groups of 5 years for men and women  Statistical and genetic analysis Prior to any other evaluations, the descriptive statistics reflecting the basic characteristics of the studied sample were computed in the whole sample and within age groups of 5 years. At the first stage we computed familial (spouses, parent-offspring and sib-sib) correlations between the corresponding TOSS levels to examine the potential genetic effect on the skeletal biomarker of BA. 2003 2 P –6 P 1974 1981 1983 1997 1999 1 gs g s (g 1 1 1 2,  2 2 2 g g g g 1  1999 2003 1995 t 0 q t 0 B 2000 Results 1 1 2 2 1 1995 3 Table 1 Familial correlations of TOSS Relatives R N P Spouses 0.08 333 0.15 Parent-offspring 0.12 755 0.002 Sib pairs 0.31 189 0.0008 Table 2 Segregation analysis for TOSS (OSS standardized in age groups of 5 years for each sex) Parameter Main models Restricted models General Mendelian Equal τ-s Arbitrary τ-s Mendelian most parsimonious Equal τ-s 1 2 3 4 5 6 P 0.600 0.628 0.252 0.558 0.598 ± 0.033 0.563 1 −0.727 −0.724 −1.080 −0.758 −0.729 ± 0.057 −0.702 2 0.481 0.525 −0.329 0.380 0.429 ± 0.061 0.362 3 0.362 0.385 0.383 0.380! 0.429! 0.362! 1 2 0.299 0.325 0.074 0.255 0.303 ± 0.045 0.289 2 2 1.074 0.988 0.504 1.165 1.067 ± 0.103  1.181 3 2 0.205 0.232 1.049 0.255! 0.303! 0.289! ρ 0.085 0.104 0.099 [0.000] [0.000] [0.000] β 0.006 −0.029 0.033 [0.000] [0.000] [0.000] ε 0.325 0.228 0.311 0.327 0.249 ± 0.067 0.327 1 0.910 [1.000] 0.272 0.916 [1.000] 0.614 2 0.632 [0.500] 0.272! 0.618 [0.500] 0.614! 3 0.001 [0.000] 0.272! 0.020 [0.000] 0.614! Log LH −1425.66 −1428.27 −1435.91 −1427.29 −1429.61 −1440.51 2 − NS 20.5** (1) NS NS 26.44** (4) P P 2 Constraints denotation: [ ]— parameter is fixed to shown value; !— parameter is constrained to be equal to the parameter above in the table Table 3 Parameters of stochastic aging models estimated for OSS data without grouping (1) and grouped according to predicted genotype (2), sex (3), or both sex and predicted genotype (4)  Parameter All 1 1 1 2 2 2 All 0 21.223 ± 0.933 21.705 ± 0.884 22.225 ± 1.179 q 0.118 ± 0.015 0.077 ± 0.010 0.217 ± 0.044 B 0.552 ± 0.004 0.518 ± 0.004 0.600 ± 0.004 TM 29.689 34.619 26.838  Model 1 (3 d.f.) Model 2 (6 d.f.) R 2 R 2 Log LH=−3476.8 Log LH=−3065.5 – 2 Men 0 20.524 ± 1.231 21.573 ± 1.142 21.886 ± 1.683 q 0.127 ± 0.024 0.098 ± 0.014 0.233 ± 0.071 B 0.501 ± 0.005 0.449 ± 0.005 0.556 ± 0.005 TM 28.400 31.740 26.182 Women 0 22.078 ± 1.342 21.840 ± 1.169 22.623 ± 1.601 q 0.107 ± 0.019 0.057 ± 0.000 0.187 ± 0.046 B 0.617 ± 0.007 0.629 ± 0.008 0.657 ± 0.007 TM 31.400 39.373 27.979  Model 3 (6 d.f.) Model 4 (12 d.f.) R 2 R 2 Log LH=−3443.3 Log LH=−3000.7 2 2 1 1 t 0 q t 0 B P −6 2 1 1  P 1 2 2 2 1 1  P Fig. 2 1 1 1 2 2 2  2004 1996 2004 Discussion In the present study, we evaluated the extent and mode of inheritance of a skeletal biomarker of BA. We constructed this biomarker (TOSS) to be maximally fitted according to the BA definition; it reflects the intensity of an individual’s skeletal changes in relation to its coevals of the same sex, and the range of the index does not depend on the age cohort. 2006b P 2005 1996 1995 2002 1994 2004 2004 2004 3 1995 t t i t i  t 0,  q B). t 0,  q 1 1  1 1 B 1 1  P 1 2 2 2 1 1  P 2005 2006 2004 2006 2004 2004 2005 1997 2005 2005 2006 2002 2000