A Modest Sample of the Flood of Longevity-Related Genes
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There are a lot of genes wherein alterations correlate with longevity - either mutations, removal of the gene, or epigenetic variations. Some of these are similar between many species, some restricted to a few small branches of the evolutionary tree. As the costs of investigating the genome and the proteome fall rapidly, ever more data is accumulated on the detailed relationships between biology and longevity at the level of molecular mechanisms.

There really is too much new work emerging to point out every study - it has become unremarkable to discover new correlations in the genetics of longevity. Also, when it comes down to it, little of this research will be of any real relevance to the most direct and important work on rejuvenation biotechnology. The research community knows more than enough to enable work on repairing the damage that causes aging.

In any case, here is a recent and representative selection from the ongoing flood of new results on genetics and longevity:

Reduction of Mitoferrin Results in Abnormal Development and Extended Lifespan in Caenorhabditis elegans

Iron is essential for organisms. It is mainly utilized in mitochondria for biosynthesis of iron-sulfur clusters, hemes and other cofactors. Mitoferrin 1 and mitoferrin 2, two homologues proteins belonging to the mitochondrial solute carrier family, are required for iron delivery into mitochondria. ... In this study we found that reduced mitoferrin levels in C. elegans by RNAi treatment causes pleiotropic phenotypes such as small body size, reduced fecundity, slow movement and increased sensitivity to paraquat. Despite these abnormities, lifespan was increased by 50% to 80% in N2 wild type strain, and in further studies using the RNAi sensitive strain eri-1, more than doubled lifespan was observed. The pathways or mechanisms responsible for the lifespan extension and other phenotypes of mitoferrin RNAi worms are worth further study, which may contribute to our understanding of aging mechanisms and the pathogenesis of iron disorder related diseases.

Activity of mannose-binding lectin (MBL) in centenarians

We analyzed MBL2 gene variants in two cohorts of centenarians, octo- and nonagenarians and in the general population, one from Sardinia island (Italy), recruited in the frame of the AKea study, and another from Campania (southern Italy), to search for haplotypes related to longevity. ...The frequency of high and null activity haplotypes was significantly lower and the frequency of intermediate activity haplotype significantly higher in centenarians and in subjects between 80 and 99 years from both the cohorts as compared each to the general population from the same geographic area.

MICS-1 interacts with mitochondrial ATAD-3 and modulates lifespan in C. elegans

Here, we provide evidence that MICS-1 is an interacting partner of the mitochondrial protein ATAD-3 (homologue of human ATAD3), which is essential for C. elegans development. We demonstrate that [RNA interference of mics-1 causes] enhanced longevity with an increased mean lifespan of up to 54% compared to control animals. Of note, also [RNA interference of atad-3] promoted longevity, although to a lesser extend (29% compared to controls).

Linkage of Cardiac Gene Expression Profiles and ETS2 with Lifespan Variability in Rats

Longevity variability is a common feature of aging in mammals, but the mechanisms responsible for this remain largely unknown. Using microarray datasets [we] identified a set of 252 cardiac transcripts predictive of relative lifespan in [rats]. ... four transcription factors (Max, Ets2, Erg, and Msx2) present in heart displayed longevity-dependent, strain-independent changes in abundance, but only ETS2 had an expression profile that directly correlated with the relative lifespan gene set. ... We conclude that variations in ETS2 abundance in hearts of adult rodents and the associated loss of CMs, contribute at least partially, to the longevity variability observed during normal aging of rats through activation of programmed necrosis.
Comments

I agree that the focus should not be on genetics, but rather on epigenetics, experimenting on which proteins and other factors affect the genome's actual expression. That is the most viable way we could begin manipulating our biology for increased longevity in the more immediate future.

In the meantime, however, I don't see how identifying genes related to certain aspects of aging could hurt the cause at all.

Posted by: David at January 19, 2012 10:10 AM

most effects on aging described so far are mediated by mitochondria, which makes it difficult to explore aging by epigenetics alone. research on model organisms reveal components for aging on the cellular level only, albeit the obviously systemic effects. thus, such results can not simply transfered to humans. in my opinion (note: the MICS-1 gene is named after my nickname), we all do not want to get older but stay young, which if getting true would induce a lot of crowding. however, a realistic aim for research on aging is to stay healthy in the time given to us.

Posted by: Michael Hoffmann at March 29, 2012 3:07 AM
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