Pioneering investigations have thrown the first scientific light on the highly unusual case of Brooke
Greenberg, a child from Baltimore, Maryland, who is 16 years old, but whose size and development
corresponds to that of an infant of 11 months.
The hope is that the investigation will throw up new clues to ageing. But the researchers involved say that
Brooke's condition is not a reversed version of conditions that lead to premature ageing.
"It's not the reciprocal," says Richard Walker of the University of South Florida College of Medicine in
Tampa, Florida, and head of the group which this week published an analysis of Brooke's condition.
Varied growth
When Walker and his colleagues sequenced Brooke's DNA, they found that the genes associated with the
premature-ageing diseases were normal, unlike the mutated versions in patients with Werner's Syndrome
and progeria. "That was the first thing we looked at," he said.
Nor does the analysis support the idea that Brooke is somehow "frozen-in-time", in perpetual infanthood.
Instead, Walker and colleagues found that different parts of her body and anatomy are maturing at different
rates.
"I think she has differential growth of her body," says Walker. "It's not growing like a unified organism, but in
fragmented parts."
Her brain, for example, is scarcely more mature than that of a newborn infant. Although she can recognise
her mother and make gestures and noises to articulate her wishes, she can't talk.
Yet her bones – although still abnormally short – are around 10 years old, as determined by the maturity of
the cells and structures. And despite being a teenager, she still has her baby teeth, with an estimated
developmental age of about eight years.
Master gene?
Investigations also trace some of her many medical problems, such as inability to swallow naturally without
choking, to staggered growth of body systems that normally grow in unison and work together. Because
Brooke's respiratory and gastrointestinal systems don't coordinate, and because her food pipe is
abnormally small, she can't swallow properly and continues to be fed through a tube to her stomach.
Walker thinks that Brooke is the first recorded case of what he describes as "developmental
disorganization". His hypothesis is that the cause is disruption of an as-yet unidentified gene, or genes, that
hold the key to ageing by orchestrating how an organism matures to adulthood, reproduces, then gradually
ages and dies.
Walker believes that Brooke lacks this "regulator" of development – first proposed in 1932 by British marine
biologist, George Parker Bidder. Like Bidder, Walker believes that the regulator guides organisms through
to adulthood, but also works beyond then to orchestrate ageing and, eventually, death.
'Important leads'
Walker says that Brooke's condition is the first that could give important leads to the identity of this master
regulator. He hopes that by investigating her condition further, and perhaps finding other cases, he may
find additional clues and leads.
The elusive regulator must be very different to the genes that cause progeria and Werner's syndrome,
Walker says. The symptoms of these diseases arise not because a master gene controlling ageing is
damaged, but because of mutations that give the appearance and manifestation of ageing through damage
to genes governing function of specific biological structures.
In progeria, for example, the decisive damage is to a gene that makes lamin A, a protein located just under
the nuclear membrane of a cell. People with progeria have a mutated version of the gene which produces
progerin, an abnormal and malfunctioning version of lamin A. This results in the symptoms of premature
ageing.
Wider search
Maria Eriksson of the Karolinska Institute in Sweden, who discovered the progeria mutation in 2003, also
thinks it unlikely that Brooke's condition relates to progeria, or to damage to the lamin A gene.
"But if you assume she has a phenomenon of slowed development, or ceased ageing, it could be worth
examining other genes related to increased life span," she says. "The klotho gene is an example of a gene,
in mice, that when mutated leads to some symptoms of premature ageing, but when it's overactive, it
extends lifespan," she says.
Other researchers have identified IGF-1 as a gene linked with prolonged life in nematode worms, mice and
humans.
Walker says that in subsequent studies, he will examine and compare Brooke's DNA in greater detail to
check for clues.
Journal reference: Mechanisms of Ageing and Development DOI: 10.1016.j.mad.2009.02.003
Greenberg, a child from Baltimore, Maryland, who is 16 years old, but whose size and development
corresponds to that of an infant of 11 months.
The hope is that the investigation will throw up new clues to ageing. But the researchers involved say that
Brooke's condition is not a reversed version of conditions that lead to premature ageing.
"It's not the reciprocal," says Richard Walker of the University of South Florida College of Medicine in
Tampa, Florida, and head of the group which this week published an analysis of Brooke's condition.
Varied growth
When Walker and his colleagues sequenced Brooke's DNA, they found that the genes associated with the
premature-ageing diseases were normal, unlike the mutated versions in patients with Werner's Syndrome
and progeria. "That was the first thing we looked at," he said.
Nor does the analysis support the idea that Brooke is somehow "frozen-in-time", in perpetual infanthood.
Instead, Walker and colleagues found that different parts of her body and anatomy are maturing at different
rates.
"I think she has differential growth of her body," says Walker. "It's not growing like a unified organism, but in
fragmented parts."
Her brain, for example, is scarcely more mature than that of a newborn infant. Although she can recognise
her mother and make gestures and noises to articulate her wishes, she can't talk.
Yet her bones – although still abnormally short – are around 10 years old, as determined by the maturity of
the cells and structures. And despite being a teenager, she still has her baby teeth, with an estimated
developmental age of about eight years.
Master gene?
Investigations also trace some of her many medical problems, such as inability to swallow naturally without
choking, to staggered growth of body systems that normally grow in unison and work together. Because
Brooke's respiratory and gastrointestinal systems don't coordinate, and because her food pipe is
abnormally small, she can't swallow properly and continues to be fed through a tube to her stomach.
Walker thinks that Brooke is the first recorded case of what he describes as "developmental
disorganization". His hypothesis is that the cause is disruption of an as-yet unidentified gene, or genes, that
hold the key to ageing by orchestrating how an organism matures to adulthood, reproduces, then gradually
ages and dies.
Walker believes that Brooke lacks this "regulator" of development – first proposed in 1932 by British marine
biologist, George Parker Bidder. Like Bidder, Walker believes that the regulator guides organisms through
to adulthood, but also works beyond then to orchestrate ageing and, eventually, death.
'Important leads'
Walker says that Brooke's condition is the first that could give important leads to the identity of this master
regulator. He hopes that by investigating her condition further, and perhaps finding other cases, he may
find additional clues and leads.
The elusive regulator must be very different to the genes that cause progeria and Werner's syndrome,
Walker says. The symptoms of these diseases arise not because a master gene controlling ageing is
damaged, but because of mutations that give the appearance and manifestation of ageing through damage
to genes governing function of specific biological structures.
In progeria, for example, the decisive damage is to a gene that makes lamin A, a protein located just under
the nuclear membrane of a cell. People with progeria have a mutated version of the gene which produces
progerin, an abnormal and malfunctioning version of lamin A. This results in the symptoms of premature
ageing.
Wider search
Maria Eriksson of the Karolinska Institute in Sweden, who discovered the progeria mutation in 2003, also
thinks it unlikely that Brooke's condition relates to progeria, or to damage to the lamin A gene.
"But if you assume she has a phenomenon of slowed development, or ceased ageing, it could be worth
examining other genes related to increased life span," she says. "The klotho gene is an example of a gene,
in mice, that when mutated leads to some symptoms of premature ageing, but when it's overactive, it
extends lifespan," she says.
Other researchers have identified IGF-1 as a gene linked with prolonged life in nematode worms, mice and
humans.
Walker says that in subsequent studies, he will examine and compare Brooke's DNA in greater detail to
check for clues.
Journal reference: Mechanisms of Ageing and Development DOI: 10.1016.j.mad.2009.02.003
http://www.newscientist.com/article/dn17379-teenage-baby-may-lack-master-ageing-gene.html