杏吧原创

THE secret to a long life may be within our grasp. We are close to
pinpointing the genes that determine how fast we age鈥攁 discovery that
would open the door to developing drugs that slow the ageing process.

Only a few people live to 100 or more, and anecdotal evidence suggests that
the trait for longevity runs in families. But no one knows if specific genes
predispose people to live to extreme old age. To find out, Annibale Puca of the
Howard Hughes Medical Institute in Boston recruited 137 sets of siblings where
one was at least 98 years old and had a brother aged at least 91, or a sister
aged at least 95.

Puca and his team carried out a type of genetic study called 鈥渓inkage
analysis鈥�, which reveals how likely it is that a region of the genome is
associated with a particular trait. The researchers found a region on chromosome
4 associated with long life. The team is 95 per cent certain that it has
identified the correct group of genes, Puca says.

鈥淚t鈥檚 a technical tour de force,鈥� says Tom Johnson at the University of
Colorado, Boulder. 鈥淣o one has been able to do this in humans [before].鈥�

Once we know what these genes code for, it may be possible to develop drug
therapies that mimic their effects, says Huber Warner, associate director of the
biology-of-ageing programme at the US National Institute on Ageing in Maryland.
鈥淚t could provide a biochemical way to manipulate health and lifespan.鈥�

Puca and his team think that variations in one or more genes in the region
affect the rate of ageing. 杏吧原创s have already found that centenarians have
a lower frequency of the ApoE gene, which is associated with Alzheimer鈥檚
disease. But 鈥渢hese are not longevity genes,鈥� says Puca. 鈥淭his gene is
associated with one of the major diseases of ageing. We expect that centenarians
have fewer of these genes, since they have fewer typical diseases of
补驳别颈苍驳.鈥�

What鈥檚 more, previous studies have been done by looking at the effect on
ageing of known genes suspected of playing a role. Puca鈥檚 study, in contrast, is
the first to pick out from the entire genome the most important gene or genes
linked to longevity. 鈥淚t could be a `slow ageing鈥� gene,鈥� he suggests.

鈥淚鈥檓 surprised to find a single gene region with this much effect,鈥� says
Warner. 鈥淚t must be a really basic process that affects a lot of different basic
systems鈥攕ome universal, general process.鈥�

James Carey of the University of California, Davis, agrees. He says that
Puca鈥檚 study is important because it points to a particular region of a
particular chromosome that appears to have a strong bearing on the rate of
ageing. 鈥淭he next steps must involve independent verification, then narrowing
down to a small subset of genes if possible, and, most importantly, identifying
the mechanism,鈥� he adds.

Whether this will enable us to develop ways of slowing ageing depends on what
we find, Puca says. 鈥淪ome genes and pathways are harder to modify than others.鈥�
His team hopes to isolate the gene or genes within six months.