麻豆传媒

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鈥檚 condition is not a reversed version of conditions that lead to premature ageing.

鈥淚t鈥檚 not the reciprocal,鈥� says 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鈥檚 condition.

Varied growth

When Walker and his colleagues sequenced Brooke鈥檚 DNA, they found that the genes associated with the premature-ageing diseases were normal, unlike the mutated versions in patients with Werner鈥檚 Syndrome and progeria. 鈥淭hat was the first thing we looked at,鈥� he said.

Nor does the analysis support the idea that Brooke is somehow 鈥渇rozen-in-time鈥�, in perpetual infanthood. Instead, Walker and colleagues found that different parts of her body and anatomy are maturing at different rates.

鈥淚 think she has differential growth of her body,鈥� says Walker. 鈥淚t鈥檚 not growing like a unified organism, but in fragmented parts.鈥�

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鈥檛 talk.

Yet her bones 鈥� although still abnormally short 鈥� 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鈥檚 respiratory and gastrointestinal systems don鈥檛 coordinate, and because her food pipe is abnormally small, she can鈥檛 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 鈥渄evelopmental disorganization鈥�. 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 鈥渞egulator鈥� of development 鈥� first proposed in 1932 by British marine biologist, . Like Bidder, Walker believes that the regulator guides organisms through to adulthood, but also works beyond then to orchestrate ageing and, eventually, death.

鈥業mportant leads鈥�

Walker says that Brooke鈥檚 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鈥檚 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

of the Karolinska Institute in Sweden, who discovered the progeria mutation in 2003, also thinks it unlikely that Brooke鈥檚 condition relates to progeria, or to damage to the lamin A gene.

鈥淏ut 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,鈥� she says. 鈥淭he klotho gene is an example of a gene, in mice, that when mutated leads to some symptoms of premature ageing, but when it鈥檚 overactive, it extends lifespan,鈥� 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鈥檚 DNA in greater detail to check for clues.

Journal reference: Mechanisms of Ageing and Development DOI: 10.1016.j.mad.2009.02.003