In search of the gene that leads to long life

Why do living organisms grow old? The answer to that question is gradually becoming clearer as rapid advances in molecular biology shed light on the structural mechanisms of aging. Currently, research into aging and longevity is advancing along two major fronts.

One is focusing research on cells, the basic building blocks of life, while the other is concentrating its studies on centenarians who have actually lived for 100 years or more.

Individual cell functions deteriorate over time. That in turn causes the body's internal organs and other vital parts to wane, leading to the aging of individuals.

To date, cellular research related to aging has adopted two major approaches: one theorizes that aging and longevity are determined by genetic factors, while the other advocates thinking that environmental factors such as stress and ultraviolet rays cause toxic substances to be produced within the cells, which in turn leads to the deterioration of cell function.

Sirtuin gene research emphasizes gene activity in the aging process. Sirtuin are a class of proteins that improve intracellular metabolic efficiency in the various organs of living creatures while also working to enhance resistance to stress. Researchers are speculating that they may delay the aging process; however, there are still too many unknowns for any definitive statement to be made.

Additionally, sirtuin are not the only genes thought to be related to aging and longevity. For example, the protein known as mTOR and its gene appear to be involved with a mechanism that works to prevent aging by restricting caloric intake. Results of an experiment reported a mouse made to excessively express the klotho gene, which was discovered by Japanese researchers, lived 30 percent longer than normal.

Something considered to have a high probability of being a harmful substance that promotes cellular aging is "active oxygen." Active oxygen is produced by mitochondria (tiny membrane-enclosed organs) within the cells when they use oxygen to produce energy for cell activity. Other causes of production include external sources such as stresses in daily life and ultraviolet rays. Active oxygen is believed to possess toxicity that is damaging to genes and cells and leads to a deterioration in cell function. It is said that the balance between active oxygen occurrence and the functions designed to defend against it is what determines the speed of the aging process.

Genes also influence energy metabolism in cells and defensive functions guarding against active oxygen.

"When primarily considering active oxygen, an integrated explanation involving both genetic and environmental factors can be used," said Naoaki Ishii, a professor at Tokai University's School of Medicine.

Genes are also the subject of analysis in research focusing on centenarians. While comparing the genes of centenarians with those of young people and members of the centenarians' families who have been living in the same environment, researchers are attempting to discover the genes affecting longevity.

Genes which are prevalent only in those aged 100 years or more have been discovered; however, so far their relationship with longevity has not been clearly established. Though SNP (single-nucleotide polymorphism) research pertaining to small differences in the DNA base sequences of individuals has advanced, researchers have not been able to study a sufficient number of centenarians and have thus been unable to determine the gene concerned with longevity.

Participants in the Archon Genomics project will work to very accurately sequence all the genetic information of 100 individuals aged 105 or older. Because changes in even extremely rare genes will be examined, expectations are growing that genes related to longevity will be able to be identified.

Nobuyoshi Hirose, clinical director of the Division of Geriatric Medicine at Keio University School of Medicine, who has conducted research in Japan on more than 500 individuals aged 100 and above, is introducing Japanese centenarians to the project.

"There is more than one gene associated with longevity and various paths may lead to them. Matters will become much clearer within the next five years," predicted Hirose.