| |
| What does the mapping of the human genome mean
for aging research? |
 |
|
|
| |
|
|
 |
How might the Human Genome Project help us
understand the aging process? |
|
| |
Controversy has long existed in scientific circles as to the precise role
genetics or environment play in the aging process and the determination
of potential life span. When reduced to the level of the cell, life span
does seem to be genetically determined. Healthy, non-cancerous somatic (or
body) cells placed in tissue culture in the laboratory will undergo a defined
number of divisions or replications, and then they stop reproducing, entering
a senescent phase. The number of divisions a cell can undergo is determined
by its genes. Of course, there are also non-genetic influences on cellular
aging. Free radical or oxidative damage (where the natural metabolism of
oxygen produces byproducts that can wreak havoc with cells' DNA) and exposure
to radiation are just two examples.
|
|
 |
Research on Lower Life Forms and
Aging |
|
| |
Work done on some of the lower life forms whose genomes have also been sequenced
has contributed much to scientists' understanding of normal aging. Caenorhabditis
elegans, the roundworm, is one of the organisms whose genome has been
fully sequenced. Scientists have found that manipulating daf-2 and daf-16,
two genes involved in the roundworm's insulin signaling pathway, can increase
its life span in the laboratory three- to five-fold. A gene mutation called
Methuselah in the fruit fly Drosophila melanogaster, another organism
whose genome is sequenced, can increase its life span by 35%. While humans
share many genes with these other life forms, we also have a far more complex
genetic structure.
|
|
|
Genes and Human Longevity |
|
| |
How much of our longevity is determined by our genes is undergoing intensive
study. Scientists have known for several years that people who live the
longest often have very long-lived children. Adoptees' life spans are more
closely correlated to those of their birthparents than to those of their
adoptive parents.
We can inherit one of several different forms of a given gene, depending
on what forms our parents carry and then pass on to us. Variants of genes
that are associated with diseases that shorten human lives have been identified,
and include the BRCA1 and BRCA2 genes of breast cancer, and apoB, associated
with high blood levels of cholesterols. Variants of other genes have been
associated with longer life spans, and inheriting these increases our
likelihood of achieving greater longevity. These "longevity assurance"
genes include apoE, ACE, HLA-DR, and PAI-1. New research that studied
the genes of sibling pairs of extreme old age also suggests that an additional
gene or genes on chromosome four may also confer longevity assurance.
|
|
|
Challenges Ahead |
|
| |
This research is exciting, but it is still in its infancy. To determine
whether a particular gene causes a disease (or longevity) and how is not
an easy task. In the case of a disease, for example, scientists must have
a clear understanding of just how the disease causes damage, which is not
always that obvious. The gene believed to be responsible for that disease
must have been clearly identified and cloned (reproduced for study purposes).
Finding what portion of that gene contains the variant sequences that might
cause a given disease is also complex, because so much of the specific sequences
of genes is still not known. And if by some lucky chance, scientists do
identify a gene with an obvious variant that appears to cause a particular
disease, they need a large enough population of people with that disease
and gene to make the results of studies statistically valid.
Most scientists believe that longevity is likely a polygenic trait, that
is, multiple genes contribute to a longer life. And, of course, environmental
factors (and the interaction between genetic and environmental factors)
are also likely to play important roles. To get at the genetic component
of longevity (or some other complex human trait) typically requires novel
types of quantitative and statistical studies usually involving families
or sibling pairs. These enable scientists to compare these families' genetic
makeup with other families with similar traits and the general population
and identify certain chromosomal sections (and eventually genes) that
are powerfully correlated to the trait in question. From there, researchers
can estimate how much of a particular trait is caused by a particular
gene. For example, scientists may implicate a gene that accounts for 40%
of the genetic effect on aging. On the other hand, these types of studies
may identify 20 or more genes that contribute much smaller effects. Only
additional research will tell.
|
|
|
|
|
| |
|
|
 |
     |
 |
previous
chapter
