Human Longevity and a New Vision of Aging Natalia S. Gavrilova, Ph.D. Leonid A. Gavrilov, Ph.D. Center on Aging NORC and The University of Chicago Chicago, USA

Myth: Aging problem is just a problem of old age Facts:  Aging problem is a problem of EVERYONE older than 10 years  Aging starts very early!  Death rates begin to increase with age after the 10 th birthday

Aging starts early – at age 10 Source: Swedish official life table, 2005

Myth: There are stages in human life, and old age is just one of them Fact:  Death rates are doubling every eight years of age, with negligible effect of menopause or retirement on this process

Smooth Increase of Risk of Death with Age U.S. population, 1999

Myth: Human beings are so complex that their aging is very special Fact:  We are not much different from worms and flies: There are general laws of aging and mortality, common for humans and many animals

Mortality of Humans and Fruit Flies

Myth: Those people who live longer are aging more slowly. Fact:  Actuarial aging rate is higher in low mortality populations with higher life expectancy. This is known as “compensation law of mortality.”

Compensation Law of Mortality Convergence of Mortality Rates with Age 1 – India, , males 2 – Turkey, , males 3 – Kenya, 1969, males 4 - Northern Ireland, , males 5 - England and Wales, , females 6 - Austria, , females 7 - Norway, , females Source: Gavrilov, Gavrilova, “The Biology of Life Span” 1991

Compensation Law of Mortality (Parental Longevity Effects) Mortality Kinetics for Progeny Born to Long-Lived (80+) vs Short-Lived Parents SonsDaughters

Common Myth: Biomedical war on aging will lead to catastrophic overpopulation.

Fact: Population changes are surprisingly small and slow in their response to a dramatic life extension.

Gavrilov, L., Gavrilova, N. Reliability theory of aging and longevity. In: Handbook of the Biology of Aging. Academic Press, 6 th edition (published recently).

High Initial Damage Load (HIDL) Idea "Adult organisms already have an exceptionally high load of initial damage, which is comparable with the amount of subsequent aging-related deterioration, accumulated during the rest of the entire adult life." Source: Gavrilov, L.A. & Gavrilova, N.S The Biology of Life Span: A Quantitative Approach. Harwood Academic Publisher, New York.

Practical implications from the HIDL hypothesis: "Even a small progress in optimizing the early-developmental processes can potentially result in a remarkable prevention of many diseases in later life, postponement of aging-related morbidity and mortality, and significant extension of healthy lifespan." Source: Gavrilov, L.A. & Gavrilova, N.S The Biology of Life Span: A Quantitative Approach. Harwood Academic Publisher, New York.

New Vision of Aging-Related Diseases

Life Expectancy at Age 80 and Month of Birth Data source: Social Security Death Master File Published in: Gavrilova, N.S., Gavrilov, L.A. Search for Predictors of Exceptional Human Longevity. In: “Living to 100 and Beyond” Monograph. The Society of Actuaries, Schaumburg, Illinois, USA, 2005, pp

Predictors of Exceptional Longevity

Approach To study “success stories” in long-term avoidance of fatal diseases (survival to 100 years) and factors correlated with this remarkable survival success Jeanne Calment ( )

Study 1 How centenarians are different from their shorter-lived sibling?

People Born in November Have Twice Higher Chances to Live to 100 Within-family study of 5,698 centenarians and their siblings survived to age 50

People Born to Young Mothers Have Twice Higher Chances to Live to 100 Within-family study of 2,153 centenarians and their siblings survived to age 50. Family size <9 children. p=0.003 p=0.007 p=0.032

Being born to Young Mother Helps Laboratory Mice to Live Longer Source: Tarin et al., Delayed Motherhood Decreases Life Expectancy of Mouse Offspring. Biology of Reproduction :

Possible explanation These findings are consistent with the 'best eggs are used first' hypothesis suggesting that earlier formed oocytes are of better quality, and go to fertilization cycles earlier in maternal life.

Study 2 How centenarians are different from their shorter-lived peers when compared at young adult age?

Physical Characteristics at Young Age and Survival to 100 A study of future centenarians when they were 30 years old using WWI civil draft registration cards

Body Build and Survival to 100

People Who Are Not ‘Stout’ Have 2.6 Times Higher Chances to Live to 100 Results of multivariate study VariableOdds Ratio P-value Medium height vs short and tall height Slender and medium build vs stout build 2.63*0.025 Farming2.20*0.016 Married vs unmarried Native born vs foreign b

Fathers With Many Children Have Higher Chances to Live to 100 Conditional (fixed-effects) logistic regression N=171. Reference level: no children VariableOdds ratio95% CIP-value 1-3 children children

Acknowledgments This study was made possible thanks to: generous support from the National Institute on Aging and the Society of Actuaries

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