infoaging guides BIOLOGY OF AGING HUMAN GENOME An introduction to aging science brought to you by the American Federation for Aging Research The DNA in humans comes in strands, and small portions of those strands are called genes. WHAT IS THE GENOME AND HOW CAN GENOMICS HELP our understanding of human WHY IS IT IMPORTANT? US UNDERSTAND AND TREAT genetics. Important resources for AGE-ASSOCIATED DISEASES? scientists include: Genome is a term referring to all of the biological information Scientists are using the knowledge • Experimental genomics necessary to create and maintain gained from the Human Genome techniques a particular organism—such as a Project, a comprehensive study The technology through human being. That information is of the human genome completed which genes are studied is a encoded into the organism’s DNA in 2003, to determine which new and exciting field called (deoxyribonucleic acid), which is genes are involved in specific experimental genomics. Now self-replicating material present metabolic or disease processes. that researchers have deci- in all of the organism’s cells. The Although using genomics to phered the human genome DNA in humans comes in strands, study something as complex as sequence, they can apply and small portions of those aging itself remains a challenge, a wide variety of molecular strands are called genes. scientists are making progress biology tools to learn more in identifying genes related to about our genes. Experimental Genes are considered the basic specific age-related diseases. genomics includes a number units of heredity. The human of techniques, including gene genome is estimated to contain HOW DO SCIENTISTS STUDY expression array analysis, about 20,000 genes, representing THE HUMAN GENOME? which looks at what DNA is two percent of its DNA. The other actively transcribed into RNA, 98 percent contains what are Since the completion of the the first step in the making of called non-coding regions. What Human Genome Project, proteins. Other newly devel- the non-coding regions are used researchers have combined the oped and emerging laboratory for is not yet entirely known, but information it yielded with the techniques include DNA chip they do have some functional availability of numerous advanced technology, genetic mapping, roles. technologies to greatly increase 2 | Infoaging Guide to the Human Genome and spectral karotyping. For HOW MIGHT GENOMICS significantly affect our lifespans more information on various RESEARCH HELP US UNDER- are different from those that affect experimental genomics tech- STAND THE AGING PROCESS? other animals. nologies, see the National Human Genome Research Controversy has long existed in Genes and human longevity Institute’s Fact Sheets About scientific circles as to the precise To what extent our longevity is Science. roles genetics or environment determined by our genes is under- play in the aging process and the going intensive study. Scientists • Comparative genomics determination of potential lifespan. have known for several years that Scientists have gained great When reduced to the level of the people who live longest often insights into the workings cell, lifespan does seem to be have very long-lived children. of cells, as well as the mol- genetically determined. Healthy, Adoptees’ lifespans are more ecules that make up cells, non-cancerous somatic (or body) closely correlated to those of their by looking at more primitive cells placed in tissue culture in the birth parents than to those of their organisms such as bacte- laboratory will undergo a defined adoptive parents. ria and yeast. More recently, number of divisions or replications, scientists have sequenced and then they stop reproducing, We can inherit one of several important laboratory animals, entering what is called a senes- different forms of a given gene, such as the mouse and the cent phase. Of course, there are depending on which forms our rat, as well as other mammals also non-genetic influences on parents carry and then pass on such as the chimpanzee, dog, cellular aging. For example, free to us. Some of these gene vari- and opossum. Researchers radicals, byproducts of the body’s ants are associated with a shorter in aging are particularly inter- natural metabolism of oxygen, lifespan because they are linked ested in sequencing the ge- are involved in a process called to certain diseases, such as nomes of long-lived animals, oxidation. Exposure to radiation is the BRCA1 and BRCA2 genes such as the naked mole rat, another example. associated with breast cancer and which has the longest lifespan apoB, which is associated with among rodents, and the capu- Research on lower life high blood levels of cholesterols. chin monkey, which can live for forms and aging Variants of other genes have been over 50 years. Work done on some of the associated with longer lifespans, lower life forms whose genomes and inheriting these increases our Sequencing the genomes of have also been sequenced has likelihood of achieving greater other organisms may yield contributed much to scientists’ longevity. Among these, perhaps insights into the human understanding of normal aging. the most important is the FOXO3A genome. Scientists can Caenorhabditis elegans, the gene, which has been validated by often identify aging-related roundworm, is one of the nine independent research groups. genes in simpler organisms. organisms whose genome has Subsequent comparison to the been fully sequenced. Scientists human genome can often help found that manipulating daf-2 A gene mutation in the fruit researchers identify similar or daf-16, genes involved in the genes in humans, helping roundworm’s insulin signaling fly can increase its lifespan them target their inquiries more pathway, can increase its by 35 percent. effectively. lifespan in the laboratory three- to five-fold. A gene mutation called Methuselah in the fruit fly Drosophila melanogaster, another organism whose genome has been sequenced, can increase its lifespan by 35 percent. While humans share many genes with these other life forms, we also have a far more complex genetic structure, so the genes that most Infoaging Guide to the Human Genome | 3 CHALLENGES AHEAD likely to play important roles. This Scientists compare these families’ contrasts with the data from yeast, genetic makeup to that of other Longevity research in genomics is flies, worms, and mice, where families with similar traits, as well exciting, but it is still in its infancy. mutation in a single gene can as the general population. This Most scientists believe that human cause an extension of lifespan. can help scientists identify certain longevity is likely a polygenic trait, Determining the genetic compo- chromosomal sections (and even- that is, multiple genes contribute nent of longevity (or some other tually genes) that are powerfully to a longer life. And of course, complex human trait) typically correlated to the trait in question. environmental factors (and the requires novel types of quantita- From there, researchers can interaction between genetic and tive and statistical studies, usually estimate how much of a particular environmental factors) are also involving families or sibling pairs. trait is caused by a particular 4 | Infoaging Guide to the Human Genome gene. For example, scientists may Award recipient, points out that ramifications. Many diseases implicate a gene that accounts for ethical researchers can collect this are known to be associated with 40 percent of the genetic effect on extremely valuable data without specific abnormal proteins; the aging. On the other hand, these jeopardizing their subjects’ rights. mapping of the genome will allow types of studies may identify 20 or scientists to learn which genes more genes that contribute much The mapping of the human code for those abnormal proteins. smaller effects. Only additional genome and the development of research will tell. new technologies will help us hone One of the most exciting areas in more rapidly on which genes are for future genomics research is THE FUTURE OF GENOMICS linked with which diseases. Rather called epigenetics. As important RESEARCH than focus on slowly teasing out as the study of genes them- one or a very few specific genes selves may be, they don’t explain An important piece of work that is that can cause a disease, scien- everything about the way an ongoing and will continue is the tists can now identify regions of 50 organism develops. For example, correlating of clinical information to 100 genes that correlate with a even identical twins with the and the mapping of the genome. A given disease. same sets of genes will gradually genotype refers to the genes one begin to show slight differences inherits; a phenotype describes Perhaps just as exciting are tech- in appearance from each other. how those genes present them- nological advances that now allow This is because genes don’t work selves as traits, such as curly hair, us to sequence the entire genome in a vacuum. They interact with blue eyes, or a predisposition to of single individuals much more the environment around them cancer. By identifying phenotypes affordably and accurately. In an in unpredictable ways and give that represent patterns of disease effort that involves AFAR through each twin a set of unique physical and noting the occurrence of those the the Archon Genomics X PRIZE, characteristics. Epigenetics, then phenotypes in large populations presented by Express Scripts, a is the study of the dance of nature or even large families, scientists competition for whole genome and nurture, as it occurs at the can then go back and correlate sequencing, the whole genome of genetic level. those phenotypes with the geno- 100 centenarians and super-cen- types the people with the disease tenarians will be soon sequenced Although the Human Genome possess. Although the issue of and contribute, we hope, to our Project was completed in 2003, “genetic privacy” arises (i.e., who understanding of the mechanisms the work of understanding the has the right to know that a person of exceptional longevity.