When nematode worms were first engineered to live significantly longer in good health, not very many years ago, it was a big deal. Today, few people beyond the life science community take much notice of each new study to result in a way to extend life in lower animals. Today I briefly scanned through the latest aging research papers referenced by PubMed and saw three separate reports of aging slowed in nematodes and flies, all published in just the past week or so.
So the world turns: the remarkable becomes unremarkable. This is where we'd like to be with human engineered longevity - for it to be an unexciting topic, well-studied, with the work of commercial development well underway, and everyone taking it for granted that healthy lifespan will be made much longer through medical science. We're not there yet, evidently.
But back to those papers, representative of the breadth of metabolic investigation and experimentation presently underway. Researchers are trying genetic alterations, drugs, and a variety of other means to change aspects of metabolism shared between worms, flies, mice, and humans. They are in search of a longer-lasting and more resilient configuration of life, one which could be brough to humans via drugs or genetic engineering. This is an ambitious undertaking, far more so than simply trying to repair the metabolism we have - but yet it will have less useful results in the end. It's a strange world we live in.
The GADD45 protein family plays an important role in stress signaling and participates in the integration of cellular response to environmental and physiological factors. GADD45 proteins are involved in cell cycle control, DNA repair, apoptosis, cell survival and aging, and inflammatory response by complicated protein-protein interactions. ... Our data show that overexpression of the D-GADD45 gene in the nervous system leads to a significantly increase of Drosophila lifespan without a decrease in fecundity and locomotor activity. The lifespan extension effect is more pronounced in males than in females, which agrees with the sex-dependent expression of this gene.
An unequivocal demonstration that mitochondria are important for lifespan comes from studies with the nematode Caenorhabditis elegans. Mutations in mitochondrial proteins [lead] to a dramatic increase in the lifespan of this organism. One theory proposes that toxicity of mitochondrial reactive oxygen species (ROS) is the cause of aging and predicts that the generation of the ROS superoxide should be low in these mutants.
Here we have measured superoxide generation in these mutants and found that it is in fact elevated, rather than reduced. Furthermore, we found that this elevation is necessary and sufficient for longevity, as it is abolished by antioxidants and induced by mild treatment with oxidants. This suggests that superoxide can act as a signal triggering cellular changes that attenuate the effects of aging. This idea suggests a new model for the well-documented correlation between ROS and the aged phenotype. We propose that a gradual increase of molecular damage during aging triggers a concurrent, gradually intensifying, protective superoxide response.
Aging is associated with increased vulnerability to chronic, degenerative diseases and death. Strategies for promoting healthspan without necessarily affecting lifespan or aging rate have gained much interest. The mitochondrial free radical theory of aging suggests that mitochondria and, in particular, age-dependent mitochondrial decline play a central role in aging, making compounds that affect mitochondrial function a possible strategy for the modulation of healthspan and possibly the aging rate.
Here we tested such a "metabolic tuning" approach in nematodes using the mitochondrial modulator dichloroacetate (DCA). We explored DCA as a proof-of-principle compound to alter mitochondrial parameters in wild-type animals and tested whether this approach is suitable for reducing reactive oxygen species (ROS) production and for improving organismal health- and lifespan.