Dear Colleagues,
We have developed research project under the title:
MECHANISMS OF LIFE SHORTENING IN HUMANS BORN BY OLD PARENTS.
and we would like to discuss it with those who might be interested
in it. Any comments and suggestions to the text printed below
would be greatly appreciated.
Thank you in advance.
Dr.Leonid A.Gavrilov, Ph.D.
Director, Center for Longevity Research
Moscow State University
Moscow, Russia
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MECHANISMS OF LIFE SHORTENING IN HUMANS BORN BY OLD PARENTS.
The general trend in modern societies is that more people now
postpone the birth of the child to older ages. People are too
busy by their business career, more people are surviving now
to the advanced ages and because of population aging there is
a shift to higher age at reproduction. Also, progress in medicine
made it technically possible to have children at very old ages.
What is the risk associated with these changes in human reproductive
age ? What will be the health and longevity of the children
born by old parents ? These are the problems that will be studied
in this research project.
The unique and novel feature of the project is that it is not restricted
by studies on relatively rare congenital malformations that become
more often for the offspring of old parents (and that is well-known),
but is mainly focused on the long-term effects of parental age on the
longevity of the major part of adult people who do not have obvious
congenital conditions.
The purpose of this study is to find out whether the paternal and
maternal age at reproduction has long-term effects on longevity
of their children. Our preliminary studies have demonstrated that
there is a specific life-shortening effect of paternal age at
reproduction on longevity of daughters only. Since only daughters
inherite paternal X chromosome, this observation indicates that
critical targets (genes) affected by age-related accumulation of
mutational load in paternal germ cells might be located in X chromosome.
These preliminary results were presented and discussed by the authors
of this project at the III European Congress of Gerontology in
Amsterdam (August-September, 1995) and published in more details in
Longevity Report (vol.10, No.54, pp.7-15, 1996). The purpose of this
project is to develop these preliminary studies further, to reconfirm
previous results and to investigate the effect of maternal age at
reproduction too, with special emphasis on the mechanisms of life
shortening in humans born by old parents.
Specifically, we shall collect and computerize the genealogical
longevity data of about 100,000 persons in addition to genealogical
longevity database for 10,000 persons we already have. This significant
increase in the sample size is of critical importance because this
is the only way to make statistically significant conclusions taking
into account great variation in life span and relatively small
proportion of progeny born by old parents in human population. Life span
for each particular person will be studied as a function of both
maternal and paternal age at reproduction controlling for other
confounding factors such as parental longevity, sex, ethnicity, social
status, geographical location, etc. In order to check the hypothesis
that critical targets (genes) for life shortening are located in
X chromosome, the specific effect of the age of the grandfather from
mother's side will be studied (since grandfather's X chromosome is
inherited from mother's side only).
The significance of the proposed research with regard to the
understanding of the biological basis of aging is determined by the
fact that this will be the first comprehensive study on the importance
of age-related accumulation of the mutational load in parental germ
cells for the longevity of the offspring in humans. In particular,
if the mitochondrial theory of aging (hypothesis that mitochondrial
DNA is a critical target in age-related oxidative damage during aging)
is correct, one can expect that high maternal age at reproduction is
associated with low offspring longevity (expected as a result of
age-related accumulation of oxidative damage to mitochondrial DNA
in maternal germ cells). Another prediction that will be tested in
this study is whether maternal longevity is more important predictor
for offspring longevity than paternal one (because of maternal
inheritance of mitochomdrial DNA).
The significance of the proposed research with regard to clinical
applications is determined by the fact that the population groups
at risk will be identified. For example, our preliminary studies
indicate that in the case of high paternal age at reproduction the
the risk group is restricted by daughters only born by fathers at
age higher than 50 years. These preliminary studies should be
reconfirmed on the samples of larger size and by taking into account
other confounding factors. The effect of mother's reproductive age
should be also studied in this research.
The results of this research project will have potential commercial
value for life insurance market and for improving life insurance
technology, since the detailed life tables will be constructed for
persons born by parents of different ages and the age-sex-specific
relative risks will be calculated as a function of parental age at
reproduction.
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