Identification of genetic markers of biological age and metabolism

• Main Authors: Weindruch, Richard H, Prolla, Tomas A, Lee, Cheol-Koo
• Format: Patent
• Language: English
• Published: 27.05.2003

A common feature of most multicellular organisms is the progressive and irreversible physiological decline that characterizes senescence. Although genetic and environmental factors can influence the aging process, the molecular basis of senescence remains unknown. Postulated mechanisms include cumulative damage to DNA leading to genomic instability, epigenetic alterations that lead to altered gene expression patterns, telomere shortening in replicative cells, oxidative damage to critical macromolecules and nonenzymatic glycation of long-lived proteins (S. M. Jazwinski, 273:54, 1996; G. M. Martin, et al., . 13:25, 1996; F. B. Johnson, et al., 96:291, 1996; K. B. Beckman and B. N. Ames, . 78:547, 1998). Factors which contribute to the difficulty of elucidating mechanisms and testing interventions include the complexity of organismal senescence and the lack of molecular markers of biological age (biomarkers). Aging is complex in that underlying mechanisms in tissues with limited regenerative capacities (e.g., skeletal and cardiac muscle, brain), which are composed mainly of postmitotic (non-dividing) cells, may differ markedly from those operative in proliferative tissues. Accordingly, approaches which provide a global assessment of senescence in specific tissues would greatly increase understanding of the aging process and the possibility of pharmaceutical, genetic or nutritional intervention. A method of measuring the biological age of a multicellular organism is disclosed. In one embodiment this method comprises the steps of obtaining a sample of nucleic acid isolated from the organism's organ, tissue or cell and determining the expression pattern of a panel of sequences within the nucleic acid that have been predetermined by either increase or decrease in response to biological aging of the organ, tissue or cell. A method of obtaining biomarkers of aging is also disclosed. This method comprises the step of comparing a gene expression profile of a young multicellular organism subject's organ, tissue or cells; a gene expression profile from a chronologically aged subject's organ, tissue or cell; and a gene expression profile from a chronologically aged but biologically younger subject's organ, tissue or cell and identifying gene expression alterations that are observed when comparing the young subjects and the chronologically aged subjects and are not observed or reduced in magnitude when comparing the young subjects and the chronologically aged but biologically younger subjects.