Thursday, October 04, 2007

Sequencing Genomes Related to Research on Aging

Flipping through some recent issues of the Journal of Gerontology: Biological Science, I was struck by the number of fascinating studies being done on the biology of aging. One piece in particular seemed a nice complement to my previous post. It was "A Proposal to Sequence Genomes of Unique Interest for Research on Aging" in Volume 62A, Number 6, June 2007 by João Pedro de Magalhães et. al. Below are some excerpts:

THE recent sequencing of genomes, including the human genome, has revolutionized biomedical research. The projected genome sequencing of a large number of mammalian species, such as several primates, will offer extraordinary opportunities for studying genome evolution and to better understand the structure and dynamics of the human genome. Most target organisms for sequencing were chosen because of their usefulness as biomedical models or because of their phylogeny in relation to the human genome to address comparative and evolutionary issues. The biology of longevity, however, has been neglected in these considerations. Yet one of the most striking and mysterious differences among mammals is the wide variability in longevity. Understanding the differences in aging rates among species is a major biological puzzle. Herein we argue that studying genome evolution across species with different life spans has the potential to change our understanding of aging processes. Thus, longevity should also be taken into consideration when selecting target organisms for sequencing. As a first step, we propose the sequencing of three organisms of unique interest for aging research: the naked mole-rat (Heterocephalus glaber) whose record longevity of 28.3 years makes it the longest-lived rodent (2), the white-faced capuchin monkey (Cebus capucinus) which can live > 50 years (3), and the bowhead whale (Balaena mysticetus), the longest-lived mammal with estimates suggesting that it may live > 200 years.

...In the same way it is possible to analyze sequence data from species with different brain sizes to obtain candidate genes, we think it is now computationally possible to analyze genome sequence data from species with different life spans for candidate genes that can be experimentally tested. Computational strategies to understand the genetic basis of differences in aging between humans and closely-related species would define a new paradigm for gerontological research. For example, nearly all vertebrates share the amyloid-ß peptide sequence associated with Alzheimer's disease in humans, yet the accumulation of Alzheimer-like changes varies widely among species. What other gene differences, one may ask, modulate the effect of the amyloid gene during aging? Mammals also show major species differences in cancer type and incidence, which may be traced to specific gene differences. As humans, and one of the longest-lived animal species, it is in our keen interest to study the genetic features that contribute to the evolution of longevity and that determine our susceptibility to age-related diseases.