Leonid and Natalia Gavrilov. Abstracts

Gerontological Society of America Annual Meeting

Gavrilova N., Gavrilov L., Evdokushkina G., Semyonova V.
Are long-lived women more prone to infertility?:
Testing the prediction of evolutionary theories of aging. [Meeting Abstract].
Gerontologist, 2003, 43 (Sp. issue): 9-9.

The purpose of this study is to test the prediction of evolutionary theory of aging that human longevity comes with the cost of impaired reproductive success (higher infertility rates, see Nature, 1998, 396: 743-746). The study is based on analysis of particularly reliable genealogical records for European aristocratic families. This dataset is appealing to use for two reasons: (1) it has high data accuracy and completeness; (2) confounding effects of socio-economic status are minimized in this socially elite group. The dataset comprised of 3,723 married women born in 1500-1875 and belonging to the upper European nobility. Every case of childlessness has been cross-checked using at least two different genealogical sources. Data analysis was based on logistic regression analyses using childlessness as a dependent variable (outcome), and woman lifespan, calendar years of birth, age at marriage, husband's age at marriage and husband's lifespan as dependent (predictor) variables. This study found that woman's high longevity have no effect on her chances to be infertile. It appears that the previous claims of high infertility among long-lived women (up to 50% of infertility rate, see Nature, 1998, 396: 743-746) are related to data incompleteness, caused by under-reporting of children in the dataset used in the earlier studies. Indeed, data cross-checking revealed that at least in 32% cases the "childleness" women did in fact had children. There is little doubt that the number of children can affect human longevity through complications of pregnancy and childbearing, through changes in socioeconomic status, etc. However, the concept of heavy infertility cost for human longevity is not supported by data, when these data are carefully cross-checked, cleaned and reanalyzed.

Gavrilov L., Gavrilova N., Semyonova V., Evdokushkina G.
Early-life seasonal programming of human longevity. [Meeting Abstract].
Gerontologist, 2003, 43 (Sp. issue): 582-582.

The purpose of this study is to explore the month-of-birth effects on adult lifespan (after age 30) -- a phenomenon found in our earlier studies (Gavrilov, Gavrilova, JAAM, 1999, 2: 365-366; and JAAM, 2001, 4: 13-30). We suggested that seasonal variation in nutrient deficiency (like vitamin deficiency in Spring), as well as seasonality of disease load, experienced in early life, may have long-lasting consequences for later-life health outcomes, including adult lifespan. In this study we addressed possible concerns that seasonal effects could be caused by statistical fluke. These concerns are addressed by analyzing more than 14,000 cross-checked lifespan records for the members of European aristocracy (1800-1880 birth cohorts). Concerns over omitted variable bias are addressed by multivariate analysis with more than 25 predictor variables (including calendar year of birth, nobility rank, ethnicity, birth order, parental lifespan, parental ages at person's birth, etc.). Concerns over inter-familial heterogeneity are addressed both by including familial predictor variables into analysis, and by taking into consideration an unobserved familial heterogeneity in multilevel models. With these significant improvements, we have validated our previous findings of strong M-shaped dependence for female lifespan on month-of-birth (with two peaks of lifespan in May and December, local minimum on August, and the deepest minimum in February, with seasonal amplitude above 2 years). The seasonal effects on hazard rate are particularly strong for ages below 50 years, which explains why other studies, focused on ages above 50 years, failed to find large season-of-birth effects. Supported in part by NIA grants.

2002

Population Association of America Annual Meeting

Biodemographic (reliability) theory of aging and longevity
Gavrilov L. A., Gavrilova N.S. Abstract published in: Population Association of America. 2002 Annual Meeting. Final Program and Abstracts, p.269.

The purpose of this study is to develop a comprehensive biodemographic theory of aging based on the systems approach (reliability theory) and our forthcoming publication on related topic (Gavrilov, Gavrilova, 2001, Journal of Theoretical Biology, 213, 4). Reliability theory is a general theory about systems failure. It allows researchers to predict the age-related failure kinetics for a system of given architecture (reliability structure) and given reliability of its components. Reliability theory predicts that even those systems that are entirely composed of non-aging elements (with a constant failure rate) will nevertheless deteriorate (fail more often) with age, if these systems are redundant in irreplaceable elements. Aging, therefore, is a direct consequence of systems redundancy. Reliability theory also predicts the late-life mortality deceleration with subsequent leveling-off, as well as the late-life mortality plateaus, as an inevitable consequence of redundancy exhaustion at extreme old ages. The theory explains why mortality rates increase exponentially with age (the Gompertz law) in many species, by taking into account the initial flaws (defects) in newly formed systems. It also explains why organisms 'prefer' to die according to the Gompertz law, while technical devices usually fail according to the Weibull (power) law. Theoretical conditions are specified when organisms die according to the Weibull law: organisms should be relatively free of initial flaws and defects. The theory makes it possible to find a general failure law applicable to all adult and extreme old ages, where the Gompertz and the Weibull laws are just special cases of this more general failure law. The theory explains why relative differences in mortality rates of compared populations (within a given species) vanish with age, and mortality convergence is observed due to the exhaustion of initial differences in redundancy levels. Overall, reliability theory has an amazing predictive and explanatory power with a few, very general and realistic assumptions. Therefore, reliability theory seems to be a promising approach for developing a comprehensive theory of aging and longevity integrating mathematical methods with specific biological knowledge.

Early Life Conditions and Later Sex Differences in Adult Lifespan
Natalia S. Gavrilova, Leonid A. Gavrilov, Galina N. Evdokushkina, and Victoria G. Semyonova. Abstract published in: Population Association of America. 2002 Annual Meeting. Final Program and Abstracts, p.288.

In this study we tested our hypothesis (and preliminary observations) that early-life conditions may determine in part the later sex differences in adult lifespan. We found that such variables as (1) father's age at person's conception, (2) parental lifespan, and (3) month of birth, have larger effects on adult lifespan (life expectancy at age 30) in females rather than males. Daughters born to particularly young fathers (below 25 years) or old fathers (above 45 years) live shorter lives, while sons are less affected by paternal age at conception. The response of progeny lifespan to exceptional parental longevity (lifespan above age 90) is particularly strong for female sex of the progeny. Women born in May or December live longer compared to those born in February, while male lifespan is less affected by the season of birth. Large family size (11+ siblings) increases daughter’s lifespan, but decreases son’s lifespan, thereby increasing the gender lifespan gap. These findings are confirmed through multivariate analysis of lifespan and hazard rates taking into account more than 20 predictor variables (including simultaneous consideration of such closely related variables as birth order, sibship size, parental ages at person’s birth) as well as observed interfamilial differences and unobserved familial heterogeneity (through multilevel modeling).

Gavrilova N.S., Gavrilov L.A.
Consanguinity And Human Longevity:
Findings From The International Centenarian Study
Gerontologist, 2001, 41: 87-87, Sp.issue

Gavrilov L.A., Gavrilova N.S.
The Effects Of Early-Life Events On Adult Lifespan Are Sex-Specific
Gerontologist, 2001, 41: 163-163, Sp.issue

In this study we explored the effects of early-life conditions on adult lifespan of 12,000 persons using methodology of follow-up study of extinct birth cohorts and the multivariate regression with nominal variables. We found that sex differences in adult life span are modulated by early-life events and conditions. Specifically, we found that such variables as (1) father's age at person's conception, (2) maternal lifespan, (3) month of birth, (4) birth order (first-born status) have a profound effects on adult lifespan (life expectancy at age 30) in females, but not in males. Daughters born to young fathers (below 30 years) or old fathers (above 50 years) live significantly shorter lives, while sons are less affected by paternal age at conception. The dependence of progeny lifespan on parental lifespan is non-linear with particularly steep slope for long-lived parents (above 90 years) and female sex of the progeny. Women born in May or December live longer compared to those born in February or August, while male lifespan is less affected by the season of birth. Supported in part by NIA grants.

Parental Age Effects on Human Longevity
L. A. Gavrilov, N. S. Gavrilova, (Center on Aging, NORC/University of Chicago, Chicago, IL, USA), G. N. Evdokushkina, V. G. Semyonova (Institute of Public Health, Moscow, Russia). Gerontology, 2001, 47(Suppl.1): 611-611.

This study is focused on the following scientific problem: does the parental age at child conception affect progeny lifespan? Our previous studies found that daughters conceived to older fathers (above age 45) live shorter lives (Gavrilov, Gavrilova, 1997, Science, 277: 17), and more research is required for understanding the mechanisms of parental age effects. These studies are also of practical importance, because persons conceived to older fathers are at higher risk of prostate cancer (Zhang et al., 1999) and Alzheimer's disease (Bertram et al., 1998).

In this study we used high-quality genealogical data for European aristocratic families where the exact lifespan and parental ages at conception are known for each person. The methodology of historical prospective study of extinct birth cohorts (born in 1800-80) was applied to individual lifespan (more than 6,000 cases per each sex) as a dependent variable in multivariate regression analysis with nominal variables. The following additional predictor variables are also taken into consideration: parental and spousal lifespan, year and month of person's birth, ethnicity and birth order.

We found that daughters conceived to older fathers live shorter lives, while sons are not affected. Maternal age effects on lifespan of adult progeny are negligible compared to effects of paternal age. Conception to old father is not dangerous when father lives more than 80 years. Surprisingly, children conceived to particularly young fathers also live shorter lives, especially in the case of long-lived fathers. This study was supported in part by grants from the National Institute on Aging.

Study of the Inheritance of Human Longevity
N. S. Gavrilova, L. A. Gavrilov (Center on Aging, NORC/University of Chicago, Chicago, IL, USA), V. G. Semyonova, G. N. Evdokushkina (Institute of Public Health, Moscow, Russia). Gerontology, 2001, 47(Suppl.1): 611-611.

Understanding the mechanisms of familial transmission of human longevity is an important, still unresolved scientific problem. Our preliminary studies found very unusual non-linear (accelerating) pattern for the dependence of offspring lifespan on parental lifespan in humans, suggesting increased genetic heterogeneity among longer-lived parents (Gavrilova et al., 1998, Human Biology, 70: 799). The purpose of this study is to validate these findings on a larger dataset (more than 12,000 cases) and to consider possible alternative explanations by controlling for the effects of other important predictors of human longevity.

In this study we collected, computerized and analyzed particularly accurate and reliable genealogical data for European aristocratic families (taken from professional data sources), where the destiny (lifespan) of each person (born in 1800-80) was traced in history. The methodology of historical prospective study of extinct birth cohorts was applied to individual lifespan as a dependent variable in multivariate regression analysis with nominal variables. To control for possible confounding effects of socio-cultural differences between families, the spousal lifespan was included into analysis as an additional predictor variable.

We found strong non-linear, accelerating pattern for the dependence of progeny lifespan on parental lifespan, even after adjusting for the effects of other predictor variables: spousal lifespan, parental ages at person's conception, year and month of person's birth, ethnicity and birth order. Daughters demonstrated particularly sharp, non-linear pattern of lifespan inheritance.

Our findings support genetic explanation for exceptional human longevity. This study was supported in part by grants from the National Institute on Aging.

Population Association of America Annual Meeting

GENDER SPECIFIC EFFECTS OF EARLY-LIFE EVENTS ON ADULT LIFESPAN
Leonid A. Gavrilov, Natalia S. Gavrilova, Galina N. Evdokushkina, and Victoria G. Semyonova.
Abstract published in: Population Association of America. 2001 Annual Meeting. Final Program and Abstracts. p.233.

In this study we found that sex differences in adult life span are modulated by early-life events and conditions. Specifically, we found that such variables as (1) father's age at person's conception, (2) parental lifespan (3) month of birth, (4) birth order (first-born status) have a profound effects on adult lifespan (life expectancy at age 30) in females, but not in males. Daughters born to particularly young fathers (below 25 years) or old fathers (above 45 years) live significantly shorter lives, while sons are less affected by paternal age at conception. The dependence of progeny lifespan on parental lifespan is non-linear with particularly steep slope for long-lived parents (above 80 years) and female sex of the progeny. Women born in May or December live longer compared to those born in February or August, while male lifespan is less affected by the season of birth. Supported in part by NIA grants.

2000

Population Association of America Annual Meeting

BIODEMOGRAPHIC STUDY OF THE BOUNDARIES FOR HUMAN LONGEVITY
Leonid A. Gavrilov, Natalia S. Gavrilova, Galina N. Evdokushkina, Victoria G. Semyonova .
Abstract published in: Population Association of America. 2000 Annual Meeting. Final Program and Abstracts. p.187.

In this study we found that the dependence of daughters' lifespan on maternal lifespan is essentially non-linear, with very weak resemblance before maternal lifespan of 85 years (regression slope of daughters lifespan on maternal lifespan, b = 0.05 ± 0.01, n = 5,117 cases) and very high additive heritability for longer lived mothers (b = 0.38 ± 0.19, n = 613). This indicates that maternal age of 85 years could be considered as a demarcation line for women's longevity. A similar study of familial transmission of human longevity from father to daughter revealed a demarcation point at 80 years. The familial transmission of human longevity from father to daughter is also non-linear with very weak resemblance before paternal lifespan of 80 years (b = 0.04 ± 0.02, n = 4,793) and very high additive heritability for longer lived fathers (b = 0.30 ± 0.14, n = 937). Supported by NIA grants AG12857, AG13698‑01 and AG16138-01A1.

HERITABILITY OF HUMAN LIFESPAN IS AFFECTED BY PARENTAL AGE AT CHILDBIRTH
Natalia S. Gavrilova, Leonid A. Gavrilov, Victoria G. Semyonova, Galina N. Evdokushkina. Abstract published in: Population Association of America. 2000 Annual Meeting. Final Program and Abstracts. p.220.

In this study we found that familial resemblance in lifespan between mothers and their children is affected by maternal age at childbirth. Specifically, both daughters and sons born to older mothers (above age 35) do not demonstrate any inheritance of maternal lifespan. The regression slope (b) of SONS' lifespan on maternal lifespan is highly significant (b = 0.11 ± 0.05; n = 3,753 cases) when the mother is young (15-34 years), but is negligible for older mothers (b = -0.01 ± 0.11, n = 792). The regression slope (b) of DAUGHTERS' lifespan on maternal lifespan is also highly significant (b = 0.21 ± 0.08, n = 1,784 cases) when the mother is young (15-34 years), but is negligible for older mothers (b = -0.01 ± 0.15, n = 351). These estimates were calculated for the range for maternal lifespan of 75-95 years. Supported by NIA grants AG12857, AG13698-01 and AG16138-01A1.

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