Current Projects

Genetics of Longevity in Twins

Principal Investigator: Terry Reed, Indiana University

Twin studies have provided evidence that genetics exert a moderate influence on human longevity (length of life).  Survival to extreme old age is also influenced by genetics as evidenced by the fact that siblings of centenarians have a four-fold higher chance of living into their 90s than do siblings of persons dying in their 70s.  Further, among centenarians, morbidity appears to be compressed into their later years.  A more recent focus has been on examining factors that are related to disease-free or healthy aging.  Although genes that promote good health may include some of those related to longevity, there is no reason to expect that genetic factors related to healthy aging are only associated with extreme longevity.  The NAS-NRC Twin Registry provides an opportunity to study disease-free aging into the seventh decade and beyond.

The Medical Follow-up Agency operates a registry of World War II white male veteran twins, born in the years 1917-1927, and originally numbering nearly 16,000 pairs.  Dr. Terry Reed, Professor, Department of Medical and Molecular Genetics, Indiana University School of Medicine, directed the latest epidemiologic questionnaire study (Q8) whose respondents provide the subjects for the current study.  A subset of pairs in the NAS-NRC twin registry were recruited where one or both pairs have reached their 70s with a trait defined as "wellness".  These twins, as of the Q8 questionnaire, reported not ever having had a heart attack, stroke, coronary bypass surgery or angioplasty, diabetes mellitus, or prostate cancer.  Blood samples are being collected for DNA extraction and immortalized cell lines established for pairs in which one of the parents of the twins lived to be over age 90. 

Initial goals were to recruit 800 pairs from Q8 respondents in which one or both co-twins met the healthy aging definition.  MFUA assisted in contacting these subjects and asking them to give their informed consent to providing specimens for genetic analysis.  Blood specimens are sent to Indiana University for DNA extraction and analysis.

Genome-wide screening has been undertaken using sib-pair methods in dizygous (DZ, fraternal) twin-pairs concordant for freedom from the diseases noted above.  Analysis of genome wide scanning on the first 93 pairs of DZ twins concordant for wellness has identified five chromosomes with linkage (lod) scores greater than 1.0.  The most interesting peak is on chromosome 4 at the exact same marker that was reported linked with extreme longevity in families where extreme longevity was inherited in an autosomal dominant fashion.  Currently additional markers in these five regions as well as candidate genes will be typed to further refine the suggested linkage.  The discordant DZ pairs can also serve as a confirmatory sample to the analysis of concordant DZ pairs.  However, it appears that the sample size in this group will be insufficient for much power because of increased morbidity and mortality, particularly in the co-twin who did not meet the wellness definition. 

A group of monozygous (MZ, identical) pairs concordant for wellness will also serve as a potential co-twin control group examining environmental influences.  Human subjects approval for this project has been granted by the Indiana University-Purdue University Indianapolis Institutional Review Board and the National Academies' Human Subjects Committee.  The data will be published in a peer review journal.