Is There a TradeOff Between the Costs of Reproduction and Longevity

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Is There a Trade-Off Between the Costs of
Reproduction and Longevity?

• Natalia S. Gavrilova
• Leonid A. Gavrilov
• Center on Aging, NORC/University of Chicago, 1155
  East 60th Street, Chicago, IL 60637

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Do longevous women have impaired fertility ?Why
is this question so important and interesting

• Scientific Significance. This is a testable
  prediction of some evolutionary theories of aging
  (disposable soma theory of aging, Westendorp,
  Kirkwood, 1998)
• Practical Importance. Do we really wish to live
  a long life at the cost of infertility? Based
  these concerns a suggestion was made
• "... increasing longevity through genetic
  manipulation of the mechanisms of aging raises
  deep biological and moral questions. These
  questions should give us pause before we embark
  on the enterprise of extending our lives
• Walter Glennon "Extending the Human Life
  Span", Journal of Medicine and Philosophy, 2002,
  Vol. 27, No. 3, pp. 339-354
• Educational Significance. Do we teach our
  students right? Impaired fertility of longevous
  women is often presented in scientific literature
  and mass media as already established fact
  (Kirkwood, 2002 Westendorp, 2002 Glennon,
  2002 Perls et al., 2002 etc.) Is it a fact or
  artifact ?

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General Methodological Principle

• Before making strong conclusions, consider all
  other possible explanations, including potential
  flaws in data quality and analysis
• Previous analysis by Westendorp and Kirkwood was
  made on the assumption of data completenessNumbe
  r of children born Number of children
  recorded
• Potential concerns data incompleteness,
  under-reporting of short-lived children, women
  (because of patrilineal structure of genealogical
  records), persons who did not marry or did not
  have children.Number of children born   gtgt
  Number of children recorded

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Test for Data Completeness

• Direct Test Cross-checking of the initial
  dataset with other data sources
• We examined 335 claims of childlessness in
  the dataset used by Westendorp and Kirkwood.
  When we cross-checked these claims with other
  professional sources of data, we  found that at
  least 107 allegedly childless women (32) did
  have children!
• At least 32 of childlessness claims proved to
  be wrong ("false negative claims") !
• Some illustrative examples
• Henrietta Kerr (16531741) was apparently
  childless in the dataset used by Westendorp and
  Kirkwood and lived 88 years. Our cross-checking
  revealed that she did have at least one child,
  Sir William Scott (2nd Baronet of Thirlstane,
  died on October 8, 1725).
•  Charlotte Primrose (17761864) was also
  considered childless in the initial dataset and
  lived 88 years. Our cross-checking of the data
  revealed that in fact she had as many as five
  children Charlotte (18031886), Henry
  (18061889), Charles (18071882), Arabella
  (1809-1884), and William (18151881).
• Wilhelmina Louise von Anhalt-Bernburg
  (17991882), apparently childless, lived 83
  years. In reality, however, she had at least
  two children, Alexander (18201896) and Georg
  (18261902).

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Test for Data Completeness (II)

• If data incompleteness exists then it should be
  particularly high among obscure families (with
  low nobility ranks).
• Prediction The percentage of  alleged
  childlessness  claims should decrease with
  increasing data quality/completeness (proxy --
  high nobility rank)
• Results We sorted the dataset used by
  Westendorp and Kirkwood in order to determine
  exactly who are these childless long-lived
  women.
• We found that most of these claims belong
  to obscure, poorly studied branches of
  genealogical trees rather than to well-documented
  families (kings, princes, counts, and earls).
• The percentage of childlessness among
  long-lived women (lifespan above 80 years, born
  before 1800) dropped from 43 in poorly
  documented families to 23 in better-studied
  families (where husbands belonged to nobility
  ranks higher than barons and baronets).
•  Conclusion At least half of the "childless"
  claims are probably false in families with lower
  nobility rank.

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Test for Data Completeness (III)

• If data incompleteness for the number of children
  exists then it should be particularly high among
  poorly documented families (with many missing
  dates).
• Prediction The percentage of  alleged
  childlessness  claims should decrease with
  increasing data quality/completeness (proxy --
  availability of  birth dates, death dates for
  spouses and marriage dates)
• Results A sample of nonagenarian women (90
  years) was split according to data completeness
• 47.5 of women were "childless" in particularly
  incomplete sample (28 of total 59 cases with some
  missing dates for spouses including marriage
  dates)
• 44.3 of women were "childless" in initial
  unsorted sample (39 of total 88 cases)
• 37.9 of women were "childless" in more complete
  sample (11 of total 29 cases with available dates
  for spouses and marriage dates)
• 25.0 of women were "childless" in the most
  complete sample (3 of total 12 cases with
  available dates for spouses and for maternal
  grand parents)

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Antoinette de Bourbon(1493-1583)

• Lived almost 90 years
• She was claimed to have only one child in the
  dataset used by Westendorp and Kirkwood Marie
  (1515-1560), who became a mother of famous Queen
  of Scotland, Mary Stuart.
• Our data cross-checking revealed that in fact
  Antoinette had 12 children!
• Marie 1515-1560
• Francois Ier 1519-1563
• Louise 1521-1542
• Renee 1522-1602
• Charles 1524-1574
• Claude 1526-1573
• Louis 1527-1579
• Philippe 1529-1529
• Pierre 1529
• Antoinette 1531-1561
• Francois 1534-1563
• Rene 1536-1566

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Point estimates of progeny number for married
aristocratic women from different birth cohorts
as a function of age at death. The estimates of
progeny number are adjusted for trends over
calendar time using multiple regression.

• Source Westendorp, R. G. J., Kirkwood, T. B. L.
  Human longevity at the cost of reproductive
  success. Nature, 1998, 396, pp 743-746

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Point estimates of progeny number for married
aristocratic women from different birth cohorts
as a function of age at death. The estimates of
progeny number are adjusted for trends over
calendar time using multiple regression.

• Source Westendorp, R. G. J., Kirkwood, T. B. L.
  Human longevity at the cost of reproductive
  success. Nature, 1998, 396, pp 743-746

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Who are these 7 remarkable longevous women with
impaired fertility?

• Antoinette de Bourbon (1493-1583), allegedly
  having one child only. However after data
  cross-checking we found that she had in fact 12
  children!
• Sophia v.Braunschweig (1541-1631), allegedly
  childless. However her husband, Poppo XVIII of
  Henneburg (1513-1574), was already 49 years old
  by the time of their marriage in 1562 ! Should
  we blame this lady for her infertility?
• In all remaining five cases there were no even
  reliable birthdates for "longevous" ladies, just
  "ABOUT" guesses!
• Anne Stanhope , born ABOUT 1497. She allegedly
  had 5 children (Henry, Anne, Mary, Elizabeth,
  Edward). Our cross-checking revealed that in
  fact she had at least 8 children! They are
  Ann, Edward, Henry, Mary, Elizabeth, Margaret,
  Catherine, Jane.
• Annabel Benn, born ABOUT 1607, allegedly had one
  child only (Elizabeth). She married at age 37
  years, assuming that the guess for her birth-date
  is correct. Also her husband Henry Grey
  (1594-1651) was already 50 years old by the time
  of their marriage in 1644 ! Should we be puzzled
  by low fertility of this couple? Moreover, our
  cross-checking revealed at least one more child
  (Anthony). Helen Hope, born ABOUT 1677. When
  we cross-checked her records, we found that she
  had not just 2 children (Charles and John), but
  at least 2 more children (Margaret and Christian)
• Dorothy North, born ABOUT 1605, allegedly
  childless. Her first husband, Richard Lennard
  (1596-1630) died just 5 years after their
  marriage in 1624/25.
• Then she spend 20 years alone as widow until she
  finally married the second husband, Challoner
  Chute in 1650. By that time she was already 45
  years old, assuming that the guess for her
  birth-date is correct.Yet, our cross-checking
  revealed that she had at least one child in the
  first marriage (Richard, died 1696)
• Margaret Dalrymple, born ABOUT 1677, had at
  least one child
• Final comment
• How is it possible to make any claims about links
  between infertility (childlessness) and longevity
  with such kind of data ?

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it is not a matter of reduced fertility, but a
case of 'to have or have not'.
Source Toon Ligtenberg Henk Brand. Longevity
does family size matter? Nature, 1998, 396, pp
743-746
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Characteristics of Our Data Sample

• 3,723 married women born in 1500-1875 and
  belonging to the upper European nobility.
• Women with two or more marriages (5) were
  excluded from the analysis in order to facilitate
  the interpretation of results (continuity of
  exposure to childbearing).
• Every case of childlessness has been checked
  using at least two different genealogical
  sources.

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Number of progeny and age at first childbirth
dependent on the age at death of married
aristocratic women

• Source Westendorp, R. G. J., Kirkwood, T. B. L.
  Human longevity at the cost of reproductive
  success. Nature, 1998, 396, pp 743-746

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• Source Westendorp, R. G. J., Kirkwood, T. B. L.
  Human longevity at the cost of reproductive
  success. Nature, 1998, 396, pp 743-746

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Conclusions

• We performed a validation study of the earlier
  findings by Westendorp and Kirkwood published in
  Nature (1998, Vol. 396, pp. 743 -746) that human
  longevity comes with a high cost of infertility
  (almost a half of longevous women were reported
  to be childless).
• We have found that high rate of childlessness
  among long-lived women is an artifact of data
  incompleteness, caused by under-reporting of
  children. After data cleaning, cross-checking and
  supplementation the association between
  exceptional longevity and childlessness has
  disappeared.
• Thus, it is important now to revise a highly
  publicized scientific concept of heavy
  reproductive costs for human longevity and to
  make corrections in related teaching curriculums
  for students.
• It is also important to disavow the doubts and
  concerns over further extension of human
  lifespan, that were recently cast in biomedical
  ethics because of gullible acceptance of the idea
  of harmful side effects of lifespan extension,
  including infertility (Glannon, 2002).
• There is little doubt that the number of children
  can affect human longevity through complications
  of pregnancies and childbearing, as well as
  through changes in socioeconomic status,  etc. 
  However,  the concept of heavy infertility cost
  of human longevity is not supported by data, when
  these data are carefully reanalyzed.

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Acknowledgments

• This study was made possible thanks to
• generous support from the National Institute on
  Aging (NIH, USA),
• and
• stimulating working environment at the Center on
  Aging, NORC/University of Chicago