Gary Ruvkun and the Science of Aging

Gary Ruvkun was awarded the Nobel Prize in Medicine today for establishing the importance of RNA as a signal molecule, independent of its role in transcribing nuclear DNA.Before he worked on RNA, Ruvkun made important contributions to theoretical understanding of aging in lab worms, C.elegans.In 1993, Cynthia Kenyon had found that incapacitating the DAF-2 gene doubled the worms lifespan.

This was extraordinary only the second life extension from a single gene.The worms were not getting any new ability, but merely disabling a gene that they already had.This indicated that DAF-2 was a life-shortening gene.

Darwinian theorists didnt think this was possible.Kenyon identified DAF-2 as the worms only insulin receptor.We think of insulin as regulating blood sugar, but worms have no blood and no blood sugar level.Long before vertebrates developed a role for insulin in regulating blood sugar, insulin was a life regulating hormone.We already knew that when the worm senses food, lifespan was shorter than when food was scarce.

Kenyon established that insulin was the signal that mediated this effect.This brings us to Ruvkuns contribution.Working in his Harvard lab a few years after Kenyons discovery, he created chimeric worms with different genomes in different tissues.He was able to disable DAF-2 just in the digestive system, or just in the muscles, or just in the nervous system.Are you guessing yet?DAF-2 in the digestive system had no effect on lifespan.DAF-2 in muscle tissue had no effect on lifespan.All of the lifespan-shortening effect of DAF-2 was accomplished through the nervous system.The message was clear in neon lights the caloric restriction effect isnt about a metabolic trade-off.

Its something decided through signal processing.When there is plenty of food, the nerves make a calculation that it would be better to die sooner; and when food is scare, the worm decides to live longer.Lifespan is not imposed on animals by physical limits or physiological tradeoffs.Lifespan is regulated, and, what is more, there is a conserved mechanism regulating lifespan in diverse species, inherited throughout the animal kingdom.Despitevast differences in life-span, shared features of aging in diverse species support the existence of a common mechanism for life-span determination.Pleiotropy, re-imaginedIn subsequent years, Ruvkuns lab screened for other genes that shorten lifespan.

He found 64 of them.Most of these genes are active in development, but they are re-purposed late in life to regulate lifespan.All eukaryotes have extensive networks of transcription factors that determine when and where genes are activated.

It would be easy for the worm to de-activate these genes later in life, but instead, the worm keeps them active, with the effect of shortening lifespan.Once again, he was able to trace the role of these same genes in different animals.Lifespan-shortening functions of the same genes are widely conserved across the animal kingdom.Discover more from Josh MitteldorfSubscribe to get the latest posts sent to your email.Type your emailSubscribe