AC5 Longevity Mutants

Mice lacking the gene to create the protein adenylyl cyclase 5 (AC5) live longer. This was accidentally discovered during research into potential heart therapies, and published earlier this year:

The new discovery, that knocking out a single cardiac gene could lengthen lifespan, was an unexpected byproduct of heart research. ... mutant mice lacking [the gene for protein] AC5 were more resistant to heart failure caused by pressure within the heart. But in the process, the research team also realised that the mutant mice lived longer than their normal counterparts. [Now] they report that the treated mice lived 30% longer and did not develop the heart stress and bone deterioration that often accompanies ageing.

Like many longevity mutations of this magnitude, this is thought to invoke the beneficial mechanisms of calorie restriction in some way. Researchers are still working on clarifying the action of the AC5 mutation, as illustrated by the latest paper on the topic:

Adenylyl Cyclase 5: A New Clue in the Search for the "Fountain of Youth"?

It is proposed that these beneficial effects may be the result of the increased activity of second messenger signaling proteins such as mitogen-activated or extracellular signal-regulated protein kinase kinase (MAPKK, also known as MEK) and extracellular signal-regulated kinase (ERK), or of enzymes such as manganese superoxide dismutase (MnSOD) that promote cell survival through protection against oxidative stress and apoptosis. These intriguing findings should stimulate additional research aimed at dissecting the complex cellular mechanisms regulated by AC isoforms and may lead to novel genetic and pharmacological approaches to delay aging-related conditions and to extend life span.

A fair number of bases covered there. "We don't really know yet, but have some places to start looking" would have been fine. Metabolism is complex; there's no end to the resouces we can productively sink into understanding the space of potential beneficial alterations to mammalian metabolic processes. Those same resouces, I feel, would be better directed to understanding how to repair the metabolism we have. After all, if you can repair age-related metabolic damage once, you can come back in ten years time and do it again - and again and again, for so long as you care to continue. If developing that possibility is on the table for the same sort of cost as developing a one-time manipulation that slows the accumulation of damage by 30%, I know which route I'd choose.

This is exactly the choice facing us today, and for some strange reason the mainstream of medical science is headed down the inferior, more costly, less effective path of metabolic manipulation. Comparatively little attention is given to the more effective strategies of repair. Changing this reality is one very good reason to support the work of the Methuselah Foundation.


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