Being Born to Young Mother is Associated with Higher Chances of Living to 100

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Being Born to Young Mother is Associated with
Higher Chances of Living to 100

• Leonid A. Gavrilov, Ph.D.
• Natalia S. Gavrilova, Ph.D.
• Center on Aging
• NORC and The University of Chicago
• Chicago, USA

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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. 1991.
The Biology of Life Span A Quantitative
Approach. Harwood Academic Publisher, New York.
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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. 1991.
The Biology of Life Span A Quantitative
Approach. Harwood Academic Publisher, New York.
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Why should we expect high initial damage load in
biological systems?

• General argument--  biological systems are
  formed by self-assembly without helpful external
  quality control.
• Specific arguments

1. Most cell divisions responsible for  DNA
   copy-errors occur in early development leading to
   clonal expansion of mutations
2. Loss of telomeres is also particularly high in
   early-life
3. Cell cycle checkpoints are disabled in early
   development

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New Vision of Aging-Related Diseases
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Life Expectancy 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. 1-49.
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Approach

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

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How centenarians are different from their
shorter-lived sibling?
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Within-Family Study of Exceptional Longevity
Cases - 1,081 centenarians born in the U.S. in
1880-1889 with known information about parental
lifespan Controls 6,413 their own
siblings Method Conditional logistic
regression Advantage Allows researchers to
eliminate confounding effects of between-family
variation
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Design of the Study
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A typical image of centenarian family in 1900
census
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Multivariate AnalysisConditional logistic
regression

• For 11 matched study, the conditional likelihood
  is given by
• Where xi1 and xi0 are vectors representing the
  prognostic factors for the case and control,
  respectively, of the ith matched set.

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Siblings Born in November Have Twice Higher
Chances to Live to 100Within-family study of
5,698 centenarians and their siblings survived
to age 50
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Maternal age and odds to live to 100 for siblings
survived to age 50
Conditional (fixed-effects) logistic regression N5,778. Controlled for month of birth, paternal age and gender. Paternal and maternal lifespan gt50 years Conditional (fixed-effects) logistic regression N5,778. Controlled for month of birth, paternal age and gender. Paternal and maternal lifespan gt50 years Conditional (fixed-effects) logistic regression N5,778. Controlled for month of birth, paternal age and gender. Paternal and maternal lifespan gt50 years Conditional (fixed-effects) logistic regression N5,778. Controlled for month of birth, paternal age and gender. Paternal and maternal lifespan gt50 years
Maternal age Odds ratio 95 CI P-value
lt20 1.73 1.05-2.88 0.033
20-24 1.63 1.11-2.40 0.012
25-29 1.53 1.10-2.12 0.011
30-34 1.16 0.85-1.60 0.355
35-39 1.06 0.77-1.46 0.720
40 1.00 Reference
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Question

• Families were quite large in the past,
  particularly those covered by genealogical
  records (large family size bias).
• Is the "young mother effect" robust to the family
  size, and is it observed in smaller families too?
• Or is it confined to extremely large families
  only?
• Approach
• To split data in two equal parts by median family
  size (9 children) and re-analyze the data in each
  group separately.

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Results

• In smaller families (less than 9 children) the
  effect of young mother is even larger (for
  siblings survived to age 50 and maternal age
  20-24 years vs 40 years)
• Odds ratio 2.23, P0.013 95CI 1.18 4.21
• Compare to larger families (more than 9
  children)
• Odds ratio 1.39, P0.188 95CI 0.85 2.27
• Conclusion
• "Young mother effect" is not confined to
  extremely large family size

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People Born to Young Mothers Have Twice Higher
Chances to Live to 100Within-family study of
2,153 centenarians and their siblings survived to
age 50. Family size lt9 children.
p0.020
p0.013
p0.043
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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 2005 72 1336-1343.

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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.

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Acknowledgments

• This study was made possible thanks to
• generous support from the National Institute on
  Aging grant R01AG028620

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Final Conclusion

• The shortest conclusion was suggested in the
  title of the New York Times article about this
  study

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