Likes Alter energy

Scientists have identified a number of genes that seem to have some effect on an animals longevity. Mostly they have been found in small, short-lived creatures whose longevity is easily studied, such as mice, fruit flies, or roundworms (C. elegans), though they frequently have analogues in humans. See here for an earlier discussion.

Of course, any gene which is important for inhibiting cancer, such as the well-known p53, will tend to improve longevity, for obvious reasons. But surprisingly, there are some longevity genes which dont have such an obvious relation to cancer, and may lengthen expected life span even when cancer is present.

Longevity genes fight cancer at its source

Over the years, biologists have discovered a handful of genes in roundworms, mice and flies that bestow a dramatic increase in lifespan on the organism that carries it – sometimes up to twice their normal life expectancy.

These genes are involved in diverse biochemical pathways including those for growth hormones, insulin, food intake and caloric restriction. But it is thought that they are all have a role in how the body responds to stress.

Julie Pinkston at the University of California in San Francisco, US, and colleagues, wondered if these longevity genes had something else in common: the power to fight cancer – a notoriously age-related disease.

Pinkston manipulated a C. elegans gene to make the worm more susceptible to cancer, and she also introduced a mutated version of the daf-2 insulin-like receptor gene, known to be longevity-enhancing. Worms with both mutations, even though they developed tumors, still lived twice as long as unmutated worms. Apparently the mutated daf-2 was doing something in addition to preventing tumors from forming.

The something else seems to be related to apoptosis:

Daf-2 seemed to protect against the lethal cancer by stimulating apoptosis – programmed cell death – which tumour cells usually avoid, the researchers say.

Its understandable that a gene which stimulates apoptosis helps fight cancer. The question is whether stimulating apoptosis also has harmful side effects. Apparently not so much in this case, if longevity is doubled anyhow.

But theres more to it than that:

One hallmark of cancerous growth is a rapid acceleration of cell division. Daf-2 also decreased the number of cell divisions in the roundworms by 50% compared to what was expected for those with the gld-1 gene, Pinkston says.

Other longevity-releated gene mutations are known in C. elegans, and when these mutations were present, the longevity effect also occurred:

The team then used the same process to test three other known longevity genes in turn against the life-shortening gld-1 gene. These three double-mutant worms also lived longer than normal roundworms. Each of the three genes (eat-2, isp-1 and clk-1) suppressed cell division, even though they did not appear to increase apoptosis.

Again, it would seem that suppressing cell division with these mutations is a net benefit for longevity, despite the need for some cell division outside of tumors. Perhaps they simply cause an animals life cycle to proceed at a slower pace.

But roundworms are rather simple animals. One wonders how such an effect would play out in a human...

----------------------------

Other references:

Longevity genes fight back at cancer - subscription required

----------------------------

Tags: cancer, longevity, lifespan, medicine, aging

One of the things thats always fascinating (or inspiring, astonishing, awe-inspiring – take your pick) about what we learn from the evolutionary history of living critters is how much very different sorts of living things have in common. This even reaches down to the level of single cells, where very similar genes can be found in mammals and yeast, even bacteria.

We also find complex subsystems with substantial similarities. So much so that the nervous system of the roundworm Caenorhabditis elegans, which has all of 302 neurons in its whole nervous system (hermaphrodite version), is routinely used as an experimental model for the nervous systems of much more complex animals.

Perhaps even more astonishing than that, however, is that it now appears some genes important for modern nervous systems existed even before there were nervous systems – in sea sponges, which are just about the most primitive animals known.

Origins Of Nervous System Found In Genes Of Sea Sponge

Scientists at the University of California, Santa Barbara have discovered significant clues to the evolutionary origins of the nervous system by studying the genome of a sea sponge, a member of a group considered to be among the most ancient of all animals.

And not only are some of the genes there, but the proteins they represent may have interacted similarly to the way that corresponding proteins interact in modern synapses.

"It turns out that sponges, which lack nervous systems, have most of the genetic components of synapses," said Todd Oakley, co-author and assistant professor in the Department of Ecology, Evolution and Marine Biology at UC Santa Barbara.

"Even more surprising is that the sponge proteins have signatures indicating they probably interact with each other in a similar way to the proteins in synapses of humans and mice," said Oakley. "This pushes back the origins of these genetic components of the nervous system to at or before the first animals ---- much earlier than scientists had previously suspected."

Other blog articles: here

Original research paper: here

Tags: synapses, neuroscience