Reviewing the List of Genes Known to be Required for Calorie Restriction to Extend Life

Calorie restriction is the most studied of methods to slow aging and extend healthy life in laboratory species. Most of the diverse life extending interventions tested in these species are in fact ways to trigger some of the same mechanisms observed to be involved in calorie restriction. Cellular responses to stress, such as low levels of nutrients or heat, converge on mechanisms such as upregulation of the maintenance processes of autophagy, leading to better cell and tissue function. In short-lived species this can have quite large effects on life span, but that effect size diminishes greatly for longer-lived species such as our own. Mice live 40% longer when on a calorie restricted diet, but while we humans exhibit similar short-term health benefits, we only live a few additional years at most when practicing calorie restriction.

Epistasis analyses using mutant strains in lower organisms such as Caenorhabditis elegans (C. elegans) have revealed genes required for the effects of calorie restriction (CR), referred to here as CR genes, and the signal pathways mediating the effects of CR. In C. elegans, a number of genes such as aak-2, daf-16, skn-1, clk-1, and pha-4 have been reported to be associated with the life-prolonging effect of CR. Some of these genes also mediate the effects of CR in mice. Previous studies also reported that mutations of single genes (referred to here as longevity genes) can extend lifespan even in ad libitum feeding animals.

Many of these genes can be functionally categorized into genes associated with nutrient sensing or metabolic responses. Among these gene mutations, reduction- or loss-of-function mutations of genes in the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) signaling consistently extend lifespan in a range of organisms. Since CR is known to decrease the plasma concentration of GH and IGF-1, the GH-IGF-1 pathway is considered an evolutionary conserved pathway for longevity and a main aspect of the mechanism of CR.

Thus far, a total of 112 CR genes in yeast, 62 in nematode, 27 in drosophila, and seven in mice have been identified . Among these genes, forkhead box protein O 3 (Foxo3) and sirtuin 1 (Sirt1) genes are common in mice, nematodes, and flies. CR and longevity gene models have elucidated signal pathways for the extension of lifespan, although the signal pathways are context dependent.

Link: https://doi.org/10.3390/nu11123068

Comments

"ad libitum feeding animals" Ever been to Golden Corral?

Posted by: Tom Schaefer at January 10th, 2020 7:33 AM

Why do the majority of the posts on this board have to denigrate any path of exploration that is not SENS related?

Why do you even focus on them if you are so confident in your own philosophy?

Posting your boiler plate "....unlikely to have any significant effect on aging...." every single time does a disservice to the space as a whole

That "strategy", if I may call its such, by no means stimulates people who invest / invested in approach #1, abandon ship and jump to your approach #2

It amplifies that there is still no cohesiveness in the longevity space, and makes people not want to invest at all

Posted by: Bob Spunge at January 10th, 2020 12:28 PM

@Bob Spunge
He is not "denigrating" in the sense of demonizing those approaches. Just saying that according to his theories those approved are meh. Too little too late.

And when the press states that "translating to human would be like 400 years" , we have to honest and time down there expectations.

Posted by: Cuberat at January 10th, 2020 12:51 PM

Do we have any proven evidence thus far that any sort of age reversal has occurred in humans with any sort of methods?

Another alternative are cyborgs, either symbiotically through machine and human as one. Or transferring our brains into a machine. Elon Musk is pushing towards that method.

Posted by: Person1234 at January 10th, 2020 12:56 PM

@Cuberat

The truth is none of the SENS approaches have translated successfully either in humans, and some, like beta-amyloid scavenging, have out right failed

Posted by: Bob Spunge at January 10th, 2020 5:37 PM

@Cuberat: "Too little, too late". I spent the evening listening to Bach on YouTube, a gorgeous series from Switzerland, including ( https://www.youtube.com/watch?v=lgexOM0RrN4 ). Look at the audience. >95% are WAY out of the Demo, and I'd say, unless something is done urgently on the longevity front, >90% will be dead in less than 15 years. Given the birth rate among native Europeans, I'll make a prediction that early classical music will be largely extinct in 20 years, and that these performances represent the halcyon moment before decline and ultimate obscurity. God forbid it!

Posted by: Tom Schaefer at January 10th, 2020 10:07 PM

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