Ageing Research Reviews 10 (2011) 115–123
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Ageing Research Reviews
journal homepage: www.elsevier.com/locate/arr
Review
Parental age and characteristics of the offspring
Yongsheng Liu ∗ , Mingxing Zhi, Xiuju Li ∗
Henan Institute of Science and Technology, Xinxiang, 453003, China
a r t i c l e
i n f o
Article history:
Received 2 June 2010
Received in revised form 8 August 2010
Accepted 16 September 2010
Key words:
Parental age
Characteristics of offspring
Intelligence
Health outcome
Longevity
Sex ratio
a b s t r a c t
The relations of an offspring to its parents are complex, and the ways in which a parent may influence the characteristics of its offspring are many. This review focuses on the relations of parental age
to intelligence, health outcomes, longevity and other characteristics of offspring. Many researchers have
demonstrated that children of older parents tend to be more intelligent than do children of younger parents, although there are also some negative findings. Either teenage or advanced parental age is associated
with risk of birth and health outcomes in offspring. Parental age at birth displays a negative association
with offspring longevity. Parental age can also influence dominant characters, sex ratio, personality and
development process of the offspring. To fully analyze the influence of parental age on the offspring is of
great significance in deciding the optimal age for parenthood.
© 2010 Elsevier B.V. All rights reserved.
1. Introduction
The relations of an offspring to its parents are complex, and
the ways in which a parent may influence the characteristics of
its offspring are many. The most interesting and general biological
problem is, of course, the relationship between parental age and the
characteristics of the offspring. Parental age has been shown to be
a major factor, if not the most important factor, in producing variability in offspring. It is well known that either teenage or advanced
parental age is associated with risk of birth and health outcomes
in offspring, and this topic has been exhaustively reviewed. Less
well known is that parental age may affect offspring’s intelligence,
longevity and many other characters.
In this paper, we try to review the relations of parental age to
eminence and intelligence, birth and health outcomes, longevity
and other characters of offspring, and discuss the mechanisms
which underlie these parental age effects. To fully analyze the influence of parental age on the offspring is obviously of interest to all
of us, and is of great significance in deciding when is the best time
to be a mother or father.
∗ Corresponding authors. Current address: Department of Biochemistry, Faculty
of Medicine, University of Alberta, Edmonton, AB, T6G 2H7, Canada.
Tel.: +1 780 435 9171; fax: +1 780 492 0886.
E-mail addresses: [email protected] (Y. Liu), [email protected] (X. Li).
1568-1637/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.arr.2010.09.004
2. The effect of parental age on eminence and intelligence
of offspring
2.1. Parental age effect on eminence of offspring
Francis Galton’s name is always associated with the dawn of
human genetics and eugenics. He believed that heredity, not just
the environment, played a role in shaping a person. He hypothesized that qualities such as intelligence were passed to each
generation through heredity. In 1869, Galton published his Heredity
Genius. This built the foundation of his work in eugenics, the term
he invented for his notion that human race could be improved upon
by selective breeding. Galton (1874) also noted the age of the parents at the birth of the eminent child, and showed that the average
age of the fathers of 100 British men of science was 36 years, and
the average age of the mothers was 30 years.
The positive relationship between parental age and eminence
of offspring was confirmed by other researchers. Redfield (1903)
listed 354 eminent men and found that only 11% of all births are
to fathers under 25, and 89% are to fathers over 25 years. Later,
Redfield (1917) found 860 eminent men whose names and birthranks (the age of the father) were recorded in the encyclopedias
because of their intellectual achievements. He noticed that the
average father was about 32 years of age when the average child
was born. But the average age of the 860 eminent persons was more
than 40 years. He considered it a law that the mental ability of the
offspring is dependent upon the age of the parent at the time of
production. To breed a race of high intellectual power early marriages should be discouraged and children should be procreated by
parents who have attained their best physical and mental develop-
116
Y. Liu et al. / Ageing Research Reviews 10 (2011) 115–123
Table 1
Age distribution of parents at birth of 299 eminent men (Ellis, 1926).
Age of range
<20
20–24
25–29
30–34
35–39
40–44
Number of fathers
Percentage of fathers
Number of mothers
Percentage of mothers
2
0.6%
1
1.1%
9
3%
14
16%
45
15%
22
25%
81
27%
23
26%
59
19%
13
15%
44
14%
11
12%
ment. Interestingly, Dufton (1932) also noticed that many eminent
men were begotten by fathers of ripe age. In order to determine
whether this can be substantiated, Dufton took the age distribution of the fathers at the birth of 1000 eminent persons from the
fourteenth edition of the “Encyclopædia Britannica”, and showed
that these ages are distinctly higher than the ages of the fathers of
100,000 children less than 1 year of age at the Census of Scotland
in 1921. Moreover, Ellis (1926) found a preponderance of elderly
fathers among the fathers of 299 eminent men (see Table 1). The
most frequent age of fatherhood is from 30 to 34. A prevalence of
elderly fathers seems indicated by the fact that the general average
falls later than this most frequent age, being 37.1 years. This reflects
the tendency for the fathers of men of genius to be elderly.
In order to test the previous studies, we investigated 100 eminent scientists (see Table 2) whose parental age at their birth could
be found in the literature and whose name appears in three books:
100 Scientists Who Shaped World History (Tiner, 2000), A Ranking of
the most Influential Scientists, Past and Present (Simmons, 2000) and
Science: 100 Scientists who Changed the World (Balchin, 2003).
Our results showed that 97% of the fathers at the birth of the
eminent scientists were over 25, and 81% of the fathers were over
30 (see Table 3). It will be noticed that the average age of the fathers
in Galton’s, Yoder’s, Ellis’ and our investigation are 36, 37.8, 37.1 and
37.4, and the average age of mothers are 30, 29.8, 31.2 and 30.1 (see
Table 4). It may well be that this is not a casual coincidence.
2.2. Parental age effect on intelligence of offspring
There is more direct evidence of a positive relationship between
parental age and intelligence (or between birth order and intelligence, since parental age and birth order are at present inextricably
interwoven) of offspring. In a study of children examined at the Illinois Institute for Juvenile Research there was found to be a definite
tendency for later-born children to exceed their earlier born siblings in intelligence quotient (Thurstone and Jenkins, 1931). This
finding was confirmed by Steckel (1931), who reported an investigation into the relationship between age of parent and intelligence
of offspring in a study of nearly 7000 children in the school system
of Sioux City, Iowa, concluded that “children born of very young
parents are less intelligent than children born of more mature parents. Below the age of 26–28 for mothers and 30–32 for fathers,
the younger the parent the less favorable is the prognosis for the
intelligence of the offspring”. Later, Punke (1939) also reported that
children of older parents tended to be more intelligent than did
children of younger parents.
Zybert et al. (1978) examined effects of maternal age on intelligence test scores in a series of over 1500 young men from the
Netherlands. A significant positive correlation between maternal
age at birth of child and test score at age 19 was found for both
birth orders in the Non-manual social class and for firstborn in the
Manual social class. Sons of older mothers had higher test scores
whether they were firstborn or secondborn, providing presumptive
evidence that effects of maternal age are present within particular birth orders. Although many studies have found that children
born to young mothers face handicaps in their educational career,
considerable debate exists as to whether these effects are real age
effects. Cohen et al. (1980) showed that the overall effect of mater-
45–49
30
10%
1
1.1%
50–54
13
4%
1
1.1%
55–59
8
2%
0
0%
60 and over
8
2%
0
0%
nal age, while very small and positive, is primarily direct, that is,
not mediated by any of the social or economic conditions included
in their model. Kalmijn and Kraaykamp (2005) examined this problem by comparing siblings who were born at different ages of their
mother. When effects of maternal age remain in sibling comparisons, they can be attributed to characteristics that change with
the age of the parents, thus they are more directly supportive of
a possible causal effect of parental age. Using data on 11742 siblings in the Netherlands born between 1918 and 1974, Kalmijn and
Kraaykamp (2005) demonstrated that there is a significant positive
effect of maternal age on children’s schooling.
It should be noted that there are some recent reports which are
not consistent with the previous studies. Malaspina et al. (2005)
found a significant inverted U-shaped relationship between paternal age and IQ scores, which was independent from a similar
association of IQ scores with maternal age. IQ scores increased from
the youngest parents to maximal scores for maternal age 25–39
years and for paternal age 25–44 years. A paternal age above 45 is
indeed associated with reduced IQ in the child. The independent
effects of maternal and paternal age on offspring cognitive capacity remained significant after correction for the effects of multiple
potentially confounding demographic and clinical factors. Recently,
Saha et al. (2009) have shown remarkable contrasting effects of
paternal and maternal age on the cognitive abilities of the offspring.
Increasing maternal age is associated with superior performance
on intelligence tests in a linear fashion whereas increasing paternal age is associated with significantly poorer performance on five
out of six of the measures tested. The reason is probably that it
is not easy to define intelligence. There are several types of intelligence and accomplishment in life does not necessarily reflect
intelligence by IQ. An eminent person (or genius) is usually defined
as the development of an individual to a high degree of competency and superiority in an occupational field. This is postulated to
be due to several factors, including (1) a certain degree of innate,
biologically determined characters (principally intelligence); (2)
individual development of the capacities; and (3) training and educational advancement leading to (4) accomplishment (Eisenstadt,
1978). It has been demonstrated that specific personality traits
such as conscientiousness and openness to experience are up to 10
times more important than IQ (Sulloway, 1996). Obviously, being
an eminent person might be a result of much more than intelligence. While the necessity of superior intelligence has historically
been equated with eminence, empirical evidence has not supported
this assumption. The degree of intelligence necessary for eminence
may be dependent on field of endeavor, but it is estimated to be
above average, and in some rare instances extremely high. Current information regarding studies of eminence and its relationship
to intelligence suggests that potential genius will most likely be
found among those high in two particular areas of ability—creative
thinking and intelligence (Rekdal, 1979).
2.3. Different explanations for the parental age effects
With regard to the mechanisms underlying the effect of parental
age on eminence and intelligence of offspring, there are several explanations. The association between parental age and SES
(socioeconomic status) is of great importance. Because parents’
Y. Liu et al. / Ageing Research Reviews 10 (2011) 115–123
117
Table 2
Parental age at the birth of 100 eminent scientists.
Names (year of birth and death)
Known for
Father’s age
Mother’s age
Agassiz, Louis (1807–1873)
Alvarez, Luis Walter (1911–1988)
Aristotle (384 BC-322BC)
Bacon, Francis (1561–1626)
Banting, Frederick (1891–1941)
Bardeen, John (1908–1991)
Becquerel, Antoine Henri (1852–1908)
Bell, Alexander Graham (1847–1922)
Bernoulli, Daniel (1700–1782)
Boas, Franz (1858–1962)
Bohr, Neils (1885–1962)
Born, Max (1882–1970)
Boyle, Robert (1627–1691)
Brahe, Tycho (1546–1601)
Burbank, Luther (1849–1926)
Byron, Augusta Ada (1815–1852)
Cavendish, Henry (1731–1810)
Compton, Arthur Holly (1892–1962)
Copernicus, Nicolaus (1473–1543)
Crick, Francis (1916–2004)
Curie, Marie (1867–1934)
Cuvier, Georges (1769–1832)
Da Gama, Vasco (1469–1524)
Daguerre, Louis (1787–1851)
Dalton, John (1766–1844)
Darwin, Charles (1809–1882)
De Broglie, Louis Victor (1892–1987)
Delbruck, Max (1906–1981)
Dirac, Paul (1902–1984)
Edison, Thomas (1847–1931)
Einstein, Albert (1879–1955)
Euler, Leonhard (1707–1783)
Faraday, Michael (1791–1867)
Fermi, Enrico (1901–1954)
Fleming, Alexander (1881–1955)
Ford, Henry (1863–1947)
Franklin, Benjamin (1706–1790)
Franklin, Rosalind Elsie (1920–1958)
Freud, Sigmund (1856–1939)
Galilei, Galileo (1564–1642)
Galton, Francis (1822–1811)
Gauss, Carl (1777–1855)
Goddard, Robert (1882–1945)
Gutenberg, Johann (1398–1468)
Harvey, William (1578–1657)
Heisenberg, Werner (1901–1976)
Herschel, William (1738–1822)
Hertz, Heinrich Rudolf (1857–1894)
Hubble, Edwin Powell (1889–1953)
Huygens, Christiaan (1629–1695)
Jenner, Edward (1749–1823)
Joliot-Curie, Irene (1897–1956)
Joule, James Prescott (1818–1868)
Kepler, Johannes (1571–1630)
Kinsey, Alfred (1894–1956)
Lamarck, Jean Baptiste (1744–1829)
Landsteiner, Karl (1868–1943)
Lavoisier, Antoine Laurent (1743–1794)
Lee, Tsung-Dao (1926–)
Lister, Joseph (1827–1912)
Lorenz, Konrad (1903–1989)
Lyell, Charles (1797–1875)
Malthus, Thomas (1766–1834)
Marconi, Guglielmo (1874–1937)
Maxwell, James Clerk (1831–1879)
Mayr, Ernst (1904–2005)
McClintock, Barbara (1902–1992)
Mead. Margaret (1901–1978)
Meitner, Lise (1878–1968)
Mendel, Gregor (1822–1884)
Mendeleev, Dmitri (1834–1907)
Montgolfier, Joseph (1740–1810)
Morgan, Thomas Hunt (1866–1945)
Moseley, Henry (1887–1915)
Newton, Isaac (1643–1727)
Nobel, Alfred (1833–1896)
Zoologist, glaciologist and geologist
Physicist and inventor
Greek Philosopher
Philosopher
Discovery of insulin
Superconductivity
Radioactivity
Invention of the telephone
Fluid mechanics
Anthropologist
The atom
Quantum mechanics
Physical properties of gases
The new astronomy
Plant breeder
Analytical engine
Discovery of hydrogen
Compton effect
The heliocentric universe
Molecular biology
Radioactivity
French naturalist and zoologist
Explorer
French artist and chemist
The theory of the atom
Evolution
Wave/particle duality
The bacteriophage
Quantum electrodynamics
Inventor of light bulb, photograph, etc.
Physicist
Eighteen-Century Mathematics
The classical field theory
Atomic physics
Penicillin
Automobie
Noted polymath
Structure of coal and grahite
Psychology of the unconscious
Astronomer
Eugenics
Mathematical genius
Liquid-fueled rocketry
Inventor and printer
Circulation of the blood
Quantum theory
The discovery of Uranus
Electromagnetic radiation
Hubble’s law
The wave theory of light
Smallpox vaccine
Transmutation of elements
First law of thermodynamics
Astronomer
Human sexuality
The foundations of biology
The blood groups
Father of modern chemistry
Physicist
Surgical sterile technique
Ethology
Modern geology
Economist
Radiotelegraph system
The electromagnetic field
Evolutionary theory
Geneticist
American cultural anthropologist
Nuclear fission
The laws of inheritance
The periodic table of elements
Hot air balloon
The chromosomal theory of heredity
Atomic number
The Newtonian revolution
Nobel prizes
31
26
60
52
42
37
32
28
33
35
30
32
61
29
54
27
27
35
33
38
39
52
39
26
33
43
46
58
36
43
32
53
30
44
65
37
49
26
41
44
39
39
23
48
29
36
31
30
29
33
49
38
34
24
23
42
50
28
30
41
49
30
36
48
44
37
26
27
40
33
51
40
27
43
36
32
24
26
33
37
35
38
27
30
27
26
45
20
36
23
34
23
37
25
32
29
21
44
41
33
24
37
21
28
30
33
24
39
26
21
29
39
26
18
23
23
22
25
29
40
30
30
24
25
22
35
41
33
31
40
34
27
30
28
28
41
39
26
20
28
118
Y. Liu et al. / Ageing Research Reviews 10 (2011) 115–123
Table 2 (Continued)
Names (year of birth and death)
Known for
Father’s age
Mother’s age
Onnes, Heike Kamerlingh (1853–1926)
Oppenheimer, J. Robert (1904–1967)
Pauling, Linus (1901–1994)
Pascal, Blaise (1623–1662)
Pasteur, Louis (1822–)
Pavlov, Ivan Petrovich (1849–1936)
Perkin, William Henry (1838–1907)
Piaget, Jean (1896–1980)
Planck, Max (1858–1947)
Priestley, Joseph (1733–1804)
Rontgen, Wilhelm Conrad (1845–1923)
Sherrington, Charles (1857–1952)
Smith, Adam (1723–1790)
Tesla, nikola (1856–1943)
Turing, Alan (1912–1954)
Van Leeuwenhoek, Antonie (1632–1723)
Virchow, Rudolf (1821–1902)
Von Neumann, John (1903–1957)
Von Helmholtz, Hermann (1821–1894)
Watson, James Dewey (1928–)
Watt, James (1736–1819)
Wright,Orville (1871–1948)
Wright, Wilbur (1867–1912)
Wundt, Wilhelm (1832–1920)
Superconductivity
The atomic era
Chemist
Pascal’s law
Causes and prevention of disease
Classical conditioning
Mauveine and Perkin triangle
Child development
Physicist
British theologian and natural philosopher
X-rays
Neurophysiology
Economist
Famous inventor
Turing machine and turing test
Father of microbiology
Cell biologist
The modern computer
The rise of German science
The structure of DNA
Steam engine
Inventor of airplane
Inventor of airplane
The founding of psychology
34
33
25
35
31
26
36
31
41
33
44
49
44
37
39
36
36
33
29
31
38
39
43
45
24
35
20
27
29
23
37.4
30.1
Average age
24
37
29
40
29
34
38
36
22
24
29
35
36
40
35
Table 3
Age distribution of parents at birth of 100 eminent scientists.
Age range
<20
20–24
25–29
30–34
35–39
Number of fathers
Percentage of fathers
Number of mothers
Percentage of mothers
0
0%
1
1.2%
3
3%
21
24.7%
16
16%
23
27.1%
24
24%
14
16.5%
23
23%
17
20.0%
education, employment, and economic wealth improve with age,
parental age influences children’s environments. As a result, children born to older parents enjoy significantly higher levels of
educational and occupational achievement than children born to
younger parents (Mare and Tzeng, 1989). As the age of parent
rises, so too does the transmission of economic, social and cultural
resources to adolescent offspring, thus parents who have children
at a later age offer more resources than do their peers who have
their children at an earlier age (Powell et al., 2006). Advancing
age may also be linked to readiness for parenthood, preferences
and tastes, energy, networks, self-efficacy and competence, and life
experiences, which in turn boost investments in children (Walter,
1986).
In 1996, Sulloway published a book entitled Born to Rebel: Birth
Order, Family Dynamics and Creative Lives, in which he assembled
a large, detailed database relating birth order to various aspects
of personality using historical records and expert raters. He found
that 23 of the 28 most radical scientific innovations (e.g., Einstein’s
theory of relativity) were supported significantly more strongly by
laterborns as compared with firstborns. For example, of scientists
prominent in the controversy over Darwinism between 1859 and
1875, laterborns were 4.6 times more likely than firstborns to be
supporters rather than opponents of Darwinism. Thus he suggested
that laterborns were more open to new ideas, rebellious and uncon-
40–44
45–49
16
16%
8
9.4%
8
8%
1
1.2%
50–54
6
6%
0
0%
55 and over
4
4%
0
0%
ventional, while firstborns were more conforming, traditional, and
identifying with parents. Sulloway’s prediction has been supported
in many recent studies (Davis, 1997; Paulhus et al., 1999; Saad et
al., 2005; Healey and Ellis, 2007).
The quality of sperm may also play a significant role. Auroux et
al. (1989) investigated the distribution of scores obtained in psychometric tests by 18-year-old male subjects, according to their
father’s age at the time of their birth. They demonstrated that the
curve of such scores produced an inverted U-shape, with maximum scores obtained when the father was at 30–34 years of age.
This result is consistent with what is observed for qualitative characteristics of spermatozoa, e.g. the proportion of normal forms and
motility, which attain their maximum values in man at 30–35 years
of age (Schwartz et al., 1981; Auroux, 1992; Levitas et al., 2007). This
observation may well explain the unusual number of the fathers of
the eminent persons were between 30 and 34 years at the time of
their birth in the investigation by Galton, Ellis, Yoder and ourselves.
However, the above several hypotheses could not explain the
phenomena that the increase in the age of the father at birth
of the son increases the son’s chances of becoming eminent, as
Dufton (1932) revealed. The parental age effects on intelligence
and eminence of offspring, according to Redfield (1903), can also
be accounted for on the ground that children inherit the mental
power which their parents have acquired. Since older parents have
Table 4
The average age of parents at the birth of eminent persons in different studies.
Object of study
Cases investigated
Father’s age
Mother’s age
Researchers
Britain Scientists
Eminent men
Eminent men
Eminent scientists
100
50
299
100
36
37.8
37.1
37.4
30
29.8
31.2
30.1
Galton (1874)
Yoder (1894)
Ellis (1926)
Our study
Y. Liu et al. / Ageing Research Reviews 10 (2011) 115–123
reached a higher degree of intellectual development than younger
parents their children, it is held, will consequently tend to be of
superior mental ability. Dufton (1932) suggested that capability
may be in some degree an acquired character, and that the old
the father the greater the chance of it being acquired. Recently,
there is increasing evidence for the inheritance of acquired characters (Liu, 2007; Jablonka and Raz, 2009). Our current understanding
of epigenetics could partly explain this Lamarckian inheritance. In
recent investigations, epigenetic changes were found to be inherited across multiple generations in chicken and mice (Arai et al.,
2009; Natt et al., 2009). Increased paternal age has an influence
on DNA integrity of sperm, increases telomere length in spermatozoa and is suggested to have epigenetic effects (Sartorius and
Nieschlag, 2010). In a recent issue of Science, Gregg et al. (2010)
provide new findings that influence current thinking about the
scale and complexity of genomic imprinting and place parental
influences on gene expression as a major player in the epigenetic
regulation of brain function. Thus it is not unreasonable to postulate
epigenetic mechanisms that could plausibly result in the parental
age effects on intelligence and eminence of offspring. This topic
also raises several other questions. For example, how do the environmental factors (such as social or economic factors) affect the
parental age effect and how large the environmental effects are?
What gene-environmental effects could be thought of?
3. The effect of parental age on birth and health outcomes
of offspring
It has been shown that very young parental age and advanced
parental age are associated with birth defects and health problems.
There is a higher miscarriage, stillbirth and infant mortality for the
children of very old and very young mothers than for the intermediate group. The age range which is optimum seems to be from
25 to 35 years (Thurstone and Jenkins, 1931). A national U.S. study
finds mortality rates lowest for infants whose mother were around
age 32 at the time of birth (Misra and Ananth, 2002). Increasing
paternal age is significantly associated with spontaneous abortion,
independent of maternal age and multiple other factors (Kleinhaus
et al., 2006). By using a large set of data from the Danish Epidemiology Science Centre, Andersen et al. (2000) found that older age
strongly increases a woman’s chances of stillbirth, miscarriage and
ectopic pregnancy. In addition, pregnant women aged 35 years or
older are at increased risk of complications in pregnancy compared
with younger women (Jolly et al., 2000). Holmes (1921) reported
that the younger mothers tend to bear the smallest children and
there is a slight increase of height and weight as the age of mother
increases. The 6-year-old children of very young mothers (20 or
less) are shorter and lighter than the children of mothers a few
years older. Now it has been well documented that teenage pregnancies are at increased risk for low birth weight (Gortzak-Uzan
et al., 2001; Chen et al., 2007, 2008) and small-for-gestational-age
births (Fraser et al., 1995; Gortzak-Uzan et al., 2001). In addition,
infants fathered by teenagers (<20 years old) also had an increased
risk of adverse birth outcomes (Reichman and Teitler, 2006; Chen
et al., 2007).
It has been shown that advanced parental age is associated
with diseases of complex aetiology and with autosomal dominant
disorders in offspring (Bray et al., 2006; Kuhnert and Nieschlag,
2004). Down syndrome is among the most common genetic diseases in humans and was already found to be strongly associated
with advanced maternal age (Cohen and Lilienfeld, 1970). The risk
of having a Down syndrome offspring increases with maternal age
from 1 in 2300 at age 20 to 1 in 45 after age 45 (Collman and Stoller,
1962). There are more conclusive data pertaining to schizophrenia: all studies identified an increased risk of schizophrenia with
119
paternal age (Bertranpetit and Fananas, 1993; Malaspina et al.,
2001, 2005; Tsuchiya et al., 2005; Perrin et al., 2007). For example,
Malaspina et al. (2001) conducted a large population-based study
(birth cohort of nearly 88,000 individuals) and identified a number of 658 schizophrenia patients. They showed that the incidence
of schizophrenia increased progressively with increasing paternal
age, the risk being 2-fold and 3-fold for offspring of fathers aged
45–49 and 50 or more years, compared with those of fathers aged
less than 25 years. There was also a significant association between
advancing paternal age and risk of autism. Reichenberg et al. (2006)
showed that offspring of men 40 years or older were 5.75 times
more likely to have autism than offspring of men younger than
30 years, after controlling for year of birth, socioeconomic status
and maternal age. There is also evidence that advanced maternal and paternal ages are independently associated with autism
(Croen et al., 2007; Durkin et al., 2008). In addition, some other
human genetic diseases were reported to be related to increased
paternal age. These disorders included bipolar disorder (Frans et
al., 2008), epilepsy (Vestergaard et al., 2005), achondroplasia, the
Apert syndrome, the Marfan syndrome and fibrodysplasia ossificans progresiva (Kram and Schneider, 1978).
A positive paternal age effect was found in some reports concerning acute lymphoblastic leukaemia (Dockerty et al., 2001;
Murray et al., 2002). According to the analysis of the Swedish Family – Cancer Database, Hemminki et al. (1999) found a parental age
effect for both leukemia and brain cancer, with the former (of about
50% excess in those over 35 years) being mediated by maternal age
and the latter (of about 25% excess) by paternal age. Zhang et al.
(1999) found an association between paternal age and the son’s
risk of prostate cancer, and demonstrated that the risk of prostate
cancer was 1.7-fold higher when the paternal age at time of birth
was above 37 years compared with fathers under 27 years, and the
association of paternal age with early onset prostate cancer (<65
years) was greater than that with late onset. By investigating about
4.3 million children with their parents, Yip et al. (2006) showed
that paternal age was significantly associated with leukaemia and
maternal age were associated with elevated risk of retinoblastoma
and leukaemia.
Some malformations are clearly associated with advanced
parental age. Bille et al. (2005) reported that both high maternal age
and high paternal age were associated cleft lip with or without cleft
palate. In a retrospective analysis of 4110 cases, an increasing risk
with paternal age was found for ventricular septal defects, atrial
septal defects and patent ductus arteriosus (Olshan et al., 1994).
Advanced paternal age was also associated with increased risk of
preauricular cyst, nasal aplasia, cleft palate, hydrocephalus, pulmonic stenosis, urethral stenosis, and hemangioma (Savitz et al.,
1991).
It has been proposed that accumulation of chromosomal aberrations and mutations during the maturation of germ cells are
responsible for increasing risks of certain diseases in offspring with
advancing parental age (Hemminki et al., 1999; Bray et al., 2006). To
investigate the association between male age and the frequency of
sperm with de novo structural chromosomal abnormalities, Sloter
et al. (2007) analyzed semen specimens collected from two groups
of 10 healthy, nonsmoking men, aged 22–28 and 65–80 years. They
detected significant increases in the frequency of sperm carrying
breaks and segmental duplications and deletions of chromosome
1 among older men compared with younger men. Older men carried twice the frequency of sperm with segmental duplications and
deletions of chromosome 1. Crow (1999) proposed that there is
a higher frequency of point mutations in males, the frequency of
which increases with age. New mutations that cause dominantly
inherited diseases are known to be more common in the children of
older fathers, and even polygenic conditions tend to increase with
paternal age. For example, the risk of schizophrenia increases with
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Y. Liu et al. / Ageing Research Reviews 10 (2011) 115–123
increased paternal age, presumably as a result of new mutations
(El-Saadi et al., 2004). According to Friedman (1981), the absolute
incidence of dominant autosomal syndromes due to mutation in
the gametes of men aged >40 years may approach 0.3–0.5%. Singh
et al. (2003) examined the relationship between age and sperm
DNA damage among men. They demonstrated that the percentage
of sperm with damaged DNA was significantly higher in men aged
36–57 years than in those aged 20–35 years. It has been suggested
that this increased DNA “fragility” in older men may contribute to
an increased risk of genetic abnormalities in the offspring. In addition, dysregulation of epigenetic processes may be an important
mechanism underlying the association between paternal age and
schizophrenia (Perrin et al., 2007).
4. Parental age and the longevity of offspring
It is well known that longer lived parents tend to have longer
lived children. Less well known is that parental age at reproduction
displayed a negative association with offspring longevity (KemkesGrottenthaler, 2004). Beeton and Pearson (1901) investigated the
age at death of over 1000 pairs of sisters and brothers and found
that the earlier born had on the average a longer life. The average
longevity of elder sisters was 59.924 and younger sisters 55.667.
The average longevity of elder brothers was 58.560 and younger
brothers 54.575. In a study of 1051 pairs of brothers and 733 pairs
of sisters where it was possible to ascertain the interval between
the births it was found that the greater the interval the less is the
expectation of life of the younger member of a pair. “A brother
born 10 years before another brother has probably 7 years greater
duration of life; a sister born 10 years before another sister has
about 6 years longer duration of life”.
In 1916, in an article entitled “the long-lived first-born” the editor of Journal of Heredity, presented a study of longevity according
to birth rank 802 cases most of whom were over 90 and all of whom
were over 80 years of age (Anon, 1916). A relatively large number,
217 out of 802, or 27.05% of first born children live to be aged; a
small percentage of aged occur in the second born, 118 out of 786,
or 15.01% and a still smaller percentage of aged occur in the third
born, 104 out of 765, or 13.59%, the succeeding birth ranks showing
only a slight further decrease. Bell (1918) examined the influence of
maternal age on the life expectancy of children. From the genealogical records of 8797 descendants of a colonial American family,
he found that children from older mothers had 45% shorter lives
than children from younger mothers. Paternal age may influence
life expectancy of the female offspring in human. A retrospective
analysis in >8500 persons from aristocratic families showed that
daughters of fathers aged >50 years died 4.4 years earlier compared
to daughters of younger fathers aged 20–29 years (Gavrilov et al.,
1997). The authors speculated that genes responsible for longevity
are located on the X chromosome and may acquire more mutations
during longer paternal life.
Over the past several decades, convincing evidence has accumulated for parental age and the longevity of offspring in animals.
Lansing (1947, 1954) was the first to investigate the effect of
parental age on life span systematically. In rotifers, the life span of
successive generations from old mothers progressively decreased,
while that of successive generations from young mothers progressively increased. The effect was reversible, however, suggesting
that no increase in deleterious mutations, but rather a nongenetic
aging factor transmitted through the maternal cytoplasm. Later,
many studies have found that older mothers have shorter lived
offspring in rotifers, duckweed, house flies, stink bugs, fruit flies,
flour beetles, mealworms and yeast. This pattern is referred to as
the “Lansing effect”, after Lansing’s widely cited work on rotifers
(Parsons, 1964; Lints and Hoste, 1977; Priest et al., 2002). Recently,
Priest et al. (2002) carried out large-scale demographic experiments to examine the direct effect of maternal age and paternal
age on offspring aging in inbred and outbred strains of the fruit fly
Drosophila melanogaster. They found that the age of mothers and,
to a lesser extent, the age of fathers can have a large influence on
both offspring longevity and the shape of the age-specific mortality
trajectory. In two independent experiments they found that older
mothers generally produced shorter lived offspring, although the
exact effect of maternal age on offspring longevity differed among
strains, suggesting that maternal age effects on progeny aging may
influence the evolution of aging.
Lansing effects are transmissible and cumulative parental age
effects. Thus the question arises as to how physiological and morphological alterations of an organism will be transmitted to the next
generation because of its parental age. In other words, one needs
to understand how the information linked to parental age is transmitted from one generation to the other and how it is accumulated
during several generations (Lints, 1978). The mechanism underlying the Lansing effect remains poorly understood. Lansing (1954)
considered aging to be the result of a factor that was transmitted
from mother to offspring via the eggs. He proposed that this factor influences longevity and also alters the pattern of reproduction.
Members of short-lived lines derived from old parents reproduced
earlier and at higher rates in succeeding generations. In contrast,
members of long-lived lines derived from young parents delayed
initial reproduction to later age classes in succeeding generations.
Lints (1978) proposed that the “information” related to parental
age effects must be transmitted from one generation to the other
through the ovule and must be different as a function of parental
age. In other words, some constituents of the successively laid eggs
may vary in a linear or cyclic way as a function of ageing; differentiation and ageing being sequential and coordinated, the original
constitution of an egg may influence the development and life-span
of the individual which will emerge from it as well as the precocious or late apparition of molecules in the eggs that this individual
will produce.
Manestar-Blazic (2004) proposed a hypothesis on transmission
of longevity based on telomere length and state of integrity. It
suggests that the longevity of the offspring is proportional to the
telomere length and inversely proportional to the telomere state
of integrity in the sperm cell and oocyte at conception. These two
characteristics of telomeres depend on the parental age. Telomeres become longer in gametes during the life course, but at the
same time mutations accumulate and cause a fast loss of repetitive sequences. Because of these two opposing aspects, there could
exist an ideal age of the parents for the transmission of maximal
longevity. Priest et al. (2002) point out that maternal age has a
greater effect than paternal age on offspring longevity because the
mother contributes most of the mRNA, lipid, carbohydrate, and
protein molecules in the zygote cytoplasm.
5. Parental age and dominant character of offspring
In genetics, Mendel’s laws are well known. Less well known is
Yarrell’s law. This law was named for William Yarrell, a British naturalist and animal breeder. It maintains that a parent of an older
breed will have more influence on the character of the offspring
than a parent of a young breed (Darwin, 1987). This law was later
supported by Michurin, who found that old varieties of fruit plants
possess a stronger capacity for transmitting their characters than
young varieties (Michurin, 1949). In D. melanogaster, the heritability of sternopleural chaeta number is influenced by the age of the
parents such that estimates based upon parents of 14 days and
more are significantly greater than those from 3-day-old parents
(Beardmore et al., 1975). Lizana and Prado (1994) compared the
Y. Liu et al. / Ageing Research Reviews 10 (2011) 115–123
offspring from crosses between heterozygous individuals of different ages, and observed an association between adult age and allele
frequencies of the offspring. The offspring of the older parents have
a greater frequency of the Adf-F allele compared to the offspring of
younger parents.
Yarrell’s law was of great interest to Darwin, as he was trying
to understand why certain breeds seemed to have a greater ability to “impress” their characters on the offspring. He believed that
“Yarrell’s law must be partly true” (Darwin, 1987). In his Pangenesis (developmental theory of heredity), Darwin (1868) proposed
that all cells of the body throw off gemmules (the embryonic form
of our modern genes) at various developmental stages and these
gemmules circulate throughout the organism and enter the sex
cells. The transmission of characteristics from parent to offspring
was explained as a consequence of the incorporation of the gemmules into gametes, and their development in the offspring. Cases
in which the characteristics of one parent dominate he believed to
be a consequence of that parent’s gemmules having some advantage in number, affinity, or vigour over those derived from the
other parent. The more gemmules there were from one parent,
the more that parent’s specific characters would predominate—and
that, it seemed, explained the dominance associated with Yarrell’s
law. It has been suggested Darwin’s so-called gemmules could
include RNAs (particularly mRNA and small RNAs), circulating DNA,
mobile elements, prions or as yet unknown molecules (Liu, 2006).
Now it is well known that circulating nucleic acids occur ubiquitously and are bioactive in living organisms. Apoptosis is the most
common form of cell death, continuing throughout life from early
stages of embryogenesis to death (Lichtenstein et al., 2001). It has
been shown that there is an enhanced apoptosis with increasing
age (Higami and Shimokawa, 2000). With the establishment that
apoptosis is the most common form of cell death and there is an
enhanced apoptosis with increasing age, the ability of circulating
nucleic acids to be incorporated into gametes and expressed in the
progeny, mechanism exists for Yarrell’s law (Liu, 2009).
6. Parental age and sex ratio of offspring
Over the past several decades, the number of male births has
shown a steady decline in developed countries. It has been suggested that the decline in the male birth rate is due to a shift
in demographics including parents’ age. For example, from the
Japanese vital statistics, Takahashi (1954) showed that, when the
mother are under 20 the sex ratio (boys to 100 girls) is higher and
then the ratio decreases gradually until the mother are about 40–49.
Matsuo et al. (2009) showed that offspring sex ratio for parental
ages over 40 were significantly smaller than ages 30–34 (0.52 vs
1.17, p = 0.029). It is proposed that levels of steroid hormones of
both parents around the time of conception are positively associated with offspring sex ratio of mammals including man (James,
2006). However, previous studies also yielded conflicting results.
Ein-Mor et al. (2010) have shown that the male-to-female sex ratio
of all the newborns was 1.05 and this ratio did not change significantly with either maternal or paternal age, indicating that sex ratio
at birth is remarkably constant.
7. Parental age and other characters of the offspring
According to Marro (1912), among the parents of 456 criminals
it was found that both young and old parents produced more criminals than were born from people of maturity (20–40 years). Thieves
predominate among the children of young parents while swindlers
and those guilty of crimes of violence were more common among
the children of parents of over 40 years.
121
In mammals, where early development takes place in an environment of maternal tissues, changing physiological conditions of
the mother constitute a changing environment which can affect
the outcome of a development process in the offspring, within the
range of variation permitted by the hereditary constitution. For
example, the age of the mother has been shown to be a major factor
in producing non-genetic variability in two different cases of inherited characters: spotting of coat and polydactyly in the guinea pig
(Wright, 1926).
8. Conclusion
Current knowledge suggests that parental age has many influences on the offspring. It is found that advanced parental age has
been associated with an increase in intelligence of offspring. It is
also shown that parental age at conception may affect the risk
of some inherited diseases, longevity and other characters in offspring. Thus the parental age may be a double-edged sword and
has both positive and negative effects on the offspring. All these
parental age effects should be taken into consideration in deciding when is the best time to be a mother or father. The need for
a better understanding of the mechanisms which underlie these
parental age effects should also be stressed.
Acknowledgements
We are deeply indebted to the reviewers and editors for their
valuable comments and suggestions.
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