pate in the Long Life Family Study which will col-
lect and parse genetic and health information
for clues to longevity. Perhaps these studies will
provide information that will help the majority of
us, who have not inherited longevity gene vari-
ants, discover how to control our environments in
ways that promote long and healthy lives.
programs, is “The older you get, the healthier
you’ve been,” rather than associating extreme old
age with sickness. Their website includes a tool to
calculate your chances of joining this elite group
living to 100.com.
Centenarians have luckily inherited two gen-
eral types of gene variants: those that are directly
protective, and normal variants of genes that,
when mutant, cause disease. Specifically, single
genes important in aging a±
Control of glucose metabolism and insulin
Immune system functioning
Cell cycle control
Lipid (cholesterol) metabolism
Response to stress
Production of antioxidant enzymes
Several studies are identifying the gene
variants and lifestyle practices that contribute
to living long and well. The New England study
is amassing the “healthy standard genome.”
Investigators at the Coriell Institute in New Jersey
are probing the genomes of the oldest old in
nursing homes. So far, what these people share
is never having had heart disease and never hav-
ing smoked. Several have had cancer, indicating
that these disorders are survivable. Researchers
at the University of Pittsburgh are pursuing gene
variants that preserve cognition. The National
Institute on Aging is currently seeking families
with more than two long-lived members living
near Boston, New York, or Pittsburgh to partici-
eople who live past 100 years are called
centenarians, and they account for 1 in
about 10,000 people. Usually they enjoy
excellent health, remaining active and engaged
in activities, then succumb rapidly to diseases
that typically claim people decades earlier. Some
never get these disorders at all. Researchers hope
that learning which gene variants and environ-
mental factors centenarians share will lead to a
better understanding of the common disorders of
later adulthood—heart disease, cancers, stroke,
type 2 diabetes mellitus, and dementias.
While the environment seems to play an
important role in the deaths of people ages 60 to
85, past that age, genes predominate. Someone
who dies at age 65 of lung cancer can probably
blame decades of smoking, but a smoker who
dies at age 101 of the same type of cancer prob-
ably had protective gene variants. Centenarians
have higher levels of HDL cholesterol than other
people, which researchers estimate adds 20 years
of life. Factors that vary widely among cente-
narians include religion, education level, socio-
economic status, ethnicity, and diet. They share
normal or low weight, not smoking, handling
stress well, and not having dementia. Women
who gave birth late in life are overrepresented,
perhaps because their reproductive systems, and
the rest of their bodies, age slowly.
Children and siblings of centenarians tend
to be long-lived too, suggesting a large inher-
ited component. The saying of the New England
Centenarian Study, one of the longest-running
Living to 100—And Beyond
regions increases, but in others, it decreases. Cell death is
not a phenomenon only of the aged. It is a normal part of
life. Clinical Application 23.4 discusses characteristics that
people who live past 100 share.
The Human Life Span
In the age-old quest for longer life, people have sampled
everything from turtle soup to owl meat to human blood. A
Russian-French microbiologist, Ilya Mechnikov, believed that
a life span of 150 years could be achieved with the help of a
steady diet of milk cultured with bacteria. He thought that
the bacteria would live in the large intestine and somehow
increase the human life span. (He died at age 71.) Ironically,
many people have died in pursuit of a literal “fountain of
aging is autoimmunity, in which the immune system turns
against the body, attacking its cells as if they were invading
Active aging begins before birth, as certain cells die as
part of the developmental program encoded in the genes.
This process of programmed cell death, called
sis), occurs regularly in the embryo, degrading
certain structures to pave the way for new ones. The num-
ber of neurons in the fetal brain, for example, is halved as
those that make certain synaptic connections are spared
from death. In the fetal thymus, T cells that do not recognize
“self” cell surfaces die, thereby building the immune system.
Throughout life, apoptosis enables organs to maintain their
characteristic shapes.
Mitosis and apoptosis are opposite, but complemen-
tary, processes. As organs grow, the number of cells in some
This woman has enjoyed
living for more than a century. Researchers are
discovering clues to good health by probing the
genomes of centenarians.
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