I'm Not Dead Yet, a Review

The INDY gene in fruit flies was one of the earlier discoveries in the genetics of longevity. The initials of the name stand for I'm Not Dead Yet, an allusion to a Monty Python scene and one of many unusual names given to fly genes. You'll find a range of posts on INDY back in the Fight Aging! archives, following the research highlights over the years.

Here is an open access review paper that provides an introduction the INDY and the present state of knowledge regarding its operation when mutated to extend fly life span:

Single gene mutations that extend life span are important tools for discovering pathways underlying aging. Of particular interest have been mutations in genes that are conserved across diverse species, since they suggest common mechanisms for aging regulation. For instance, mutations in insulin signaling genes affect the life span of yeast, worms, fruit flies, and mice ... Mutations in the Indy (I'm Not Dead Yet) gene dramatically extend the life span of the fruit fly, Drosophila melanogaster. Indy encodes the fly homolog of a mammalian di and tricarboxylate transporter involved in regulating plasma and liver levels of citrate and other Krebs cycle intermediates.


Reduced expression of fly Indy or two of the C. elegans Indy homologs leads to an increase in life span. Fly and worm tissues that play key roles in intermediary metabolism are also the places where Indy genes are expressed. One of the mouse homologs of Indy (mIndy) is mainly expressed in the liver. It has been hypothesized that decreased INDY activity creates a state similar to caloric restriction (CR). This hypothesis is supported by the physiological similarities between Indy mutant flies on high calorie food and control flies on CR.


Flies, worms, and mice show similar physiological changes when INDY expression is reduced, suggesting an evolutionarily conserved role for INDY in the regulation of metabolism. ... The studies on mice further suggest protection from metabolic syndrome and insulin resistance, whether the causative factors are diet or age. INDY is thus an attractive drug target for the amelioration of metabolic disorders associated with diet or advanced age, separate from any effects on longevity.

This is one amongst many longevity-related genes, with likely many more yet to come. There is no shortage of opportunity for research groups wanting to work on the slow and incremental side of the road to the future of human longevity - to produce old-style drugs that change the long term operation of metabolism. The opportunities are there, but this is far from the best path to extending healthy human life spans.

As regular readers know, there is another path forward - the SENS vision of biotechnologies based on repair of damage rather than slowing down the rate of damage. This is likely to be no more costly [and] yet will produce at the end of the day a true cure for aging, not just a marginal benefit and a couple of extra years of life.

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