The State of Knowledge of Longevity Genes

A little while back I linked to a paper outlining the present state of knowledge of longevity genes:

Ample evidence from model organisms has indicated that subtle variation in genes can dramatically influence lifespan. The key genes and molecular pathways that have been identified so far encode for metabolism, maintenance- and repair mechanisms that minimize age related accumulation of permanent damage. Here, we describe the evolutionary conserved genes that are involved in lifespan regulation of model organisms and humans, and explore the reasons of discrepancies that exist between the results found in the various species. In general, the accumulated data has revealed that when moving up the evolutionary ladder, together with an increase of genome complexity, the impact of candidate genes on lifespan becomes smaller. ... currently used methodologies may have only little power and validity to reveal genetic variation in the population. In conclusion, although the study of model organisms has revealed potential candidate genetic mechanisms determining aging and lifespan, to what extent they explain variation in human populations is still uncertain.

Here's more in the same vein - there's no shortage of groups working to pull together a synthesis of research into aging and the genome from the past decade. The sheer amount of data that present day biotechnologies can demonstrate is daunting, however. Bioinformatics is as much a science of data management as anything else.

The genetics of ageing: insight from genome-wide approaches in invertebrate model organisms

Intense effort has been directed at understanding pathways modulating ageing in invertebrate model organisms. Prior to this decade, several longevity genes had been identified in flies, worms and yeast. More recently [it] has become routine to perform genome-wide screens for phenotypes of interest. A number of worm screens have now been performed to identify genes whose reduced expression leads to longer lifespan

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Interestingly, these screens have linked previously unidentified cellular pathways to invertebrate ageing. More surprising, however, is the sheer number of longevity genes in worms and yeast.

Contining the "daunting mass of data" theme, it's worth noting that correlations between genes and longevity form but a small part of the puzzle. The bigger portion is how the expression of genes - the process of creating proteins that go on to play their part in biological machinery - change with aging, with other changes in gene expression, with environmental circumstances, with metabolic changes ... it's a big, dynamic, complex system in any organism.

Genomic studies in ageing research: the need to integrate genetic and gene expression approaches

Genome-wide and hypothesis-based approaches to the study of ageing and longevity have been dominated by genetic investigations. To identify essential mechanisms of a complex trait such as ageing in higher species, a holistic understanding of interacting pathways is required. More information on such interactions is expected to be obtained from global gene expression analysis if combined with genetic studies.

Genetic sequence variation often provides a functional gene marker for the trait, whereas a gene expression profile may provide a quantitative biomarker representing complex cellular pathway interactions contributing to the trait. Thus far, gene expression studies have associated multiple pathways to ageing including mitochondrial electron transport and the oxidative stress response. However, most of the studies are underpowered to detect small age-changes. A systematic survey of gene expression changes as a function of age in human individuals and animal models is lacking.

Maps of gene expression changes in different tissues with aging are slowly being constructed - you might recall recent news of the mouse AGEMAP project, for example. A lot more work remains on this path, however.

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