BU researchers identify genetic signatures of exceptional longevity
in re-published study
January 26, 2012 -While environment and
family history are factors in healthy aging,
genetic variants play a critical and complex
role in conferring exceptional longevity,
according to researchers from the Boston
University Schools of Public Health and
Medicine, Boston Medical Center, IRCCS
Multimedica in Milan, Italy, and Yale
University.
Published in PLoS
ONE, after peer review, the research
findings are the corrected version of work
originally published in Science in July
2010. The revised publication includes
additional authors who independently
assessed and helped to produce a valid
genotype data set, for which the same
analysis as in the original paper was
performed.
It also contains an additional replication
data set of subjects with an average age of
107.
Centenarians are a model of healthy aging,
as the onset of disability in these
individuals is generally delayed until they
are well into their mid-90s.
Because exceptional longevity can run
strongly in families, and numerous animal
studies have suggested a strong genetic
influence on life span, the researchers set
out to determine which genetic variants play
roles in human survival beyond 100 years of
age.
They used a well-established Bayesian
statistical method for determining which
single nucleotide polymorphisms (SNPs, or
genetic variants) could, as a group, be used
to categorize subjects as centenarians
versus controls, based solely upon the
genetic information.
The predictive sensitivity of the model they
developed, which contains 281 SNPs,
increased with the age of the subject,
supporting the hypothesis that genes play an
increasingly strong role in survival in
centenarians.
The model was able to predict exceptional
longevity with 60 to 85 percent accuracy,
depending on the average age of the
replication sample that was used. The older
the sample, the stronger the sensitivity.
Many of the 130 known genes associated with
the SNPs in the prediction model have been
shown by other gerontologists to play roles
in age-related diseases and aging, said the
study's lead researchers, Paola Sebastiani,
PhD, professor of biostatistics at the BU
School of Public Health, and Thomas Perls,
MD, MPH, associate professor of medicine at
the BU School of Medicine.
"This is a useful step towards meaningful
predictive medicine and personal genomics,"
said Dr. Perls, a geriatrician at Boston
Medical Center. "When people can do this
kind of analysis on whole genome sequences
for traits that have important genetic
components, the predictive value should be
even better."
The new study differs from the earlier
study, voluntarily retracted by the authors,
in several ways: A select group of faulty
SNPs was eliminated from this study ;an
additional sample of extremely old study
subjects was added; and researchers from
Yale University were called in to
independently validate the data and
methodology.
The corrected study, as did the original,
found that subjects who shared the same
profile of variations for genetic markers in
the model appeared to share similar levels
of risk for various traits or diseases
associated with exceptional longevity --
most notably, in their ages of survival.
"Further study of these genetic
characteristics may yield a better
understanding of the genetic and biological
bases of delaying or escaping age-related
diseases and achieving longer survival," Dr.
Perls said."The novel approach to genetic
data that is described here is likely
applicable to other complex inherited
traits, and we look forward to other
research groups applying these methods to
their data."
