Fight Aging!

I noticed a rather interesting open access paper the other day: researchers found strong similarities in the gene expression changes with age in several types of mice. On the one hand normally aging mice, on the other hand various long-lived mice (calorie restricted, Ames dwarf mice, etc), and on the third hand progeroid mice suffering from a form of accelerated aging. Changes in gene expression represent, amongst other things, a part of the feedback loop whereby an organism responds to circumstances by changing its own cellular programming. Calorie restriction is a great example of that in action, and demonstrates that this sort of evolved metabolic reprogramming can make a real difference to health and lifespan.

In all the mice examined, the same sorts of gene expression changes were kicking in:

Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice. Subsequent analysis of significantly over-represented biological processes revealed suppression of the endocrine and energy pathways with increased stress responses

...

we subsequently confirmed these findings on an independent aging cohort. The majority of genes showed similar expression changes.

Our tissues react to stress in the same way, whether that stress is accelerated aging, calorie restriction, or the biochemical damage of normal aging. This is a beneficial adaptation - as calorie restriction demonstrates - but it isn't enough to hold back the consequences of either accelerated aging or the accumulated damage of very late stage "normal" aging.

The angle of the researchers here is the search for biomarkers of aging and predictors of longevity. They believe that because so many different biological states cue the same responses, you must look at gene expression of the whole genome to determine whether the state is good or bad:

The correlations we found between certain groups of mice are most likely due to distinct groups of differentially expressed genes, i.e. there might be one large set of genes similarly affected in short-lived and long-lived mice and a separate large group of genes similarly affected in progeroid and naturally aged mice. This appears indeed to be the case. Nonetheless, there are also groups of genes, such as genes of the somatotropic axis that are similarly affected in accelerated, delayed and natural aging.

...

However, the [progeroid] and long-lived animals employed in this study had a biological age of ~50% and 10-15% of their lifespan respectively. Thus, these findings also indicate that a genome-wide correlation analysis may serve as a powerful tool to determine the biological age of animals and might hence allow prognosis of longevity.

Determination of biological age is indispensable for the assessment of anti-aging treatments. Although reliable biomarkers of aging are long sought after, they have yet remained elusive. To this end, single genes or limited sets of genes used as biomarkers of aging may poorly reflect a true biological age; ... In diagnostic terms, a CR treatment might [induce] a similar age-related biomarker [as] treatment with a DNA damaging agent does.

We, therefore, propose the facilitation of comprehensive genome-wide correlation analyses to evaluate pro- and anti-aging effects of treatments aimed at health-span extension.