January 03, 2018
Pramod Pathak
By studying the effects of starvation on yeast, It has been discovered that sugar accelerates aging and premature death, in part by activating two genes known as Ras and PKA, both of which are known to accelerate aging. Longo explains:
"At Walford, we were working with human samples and mice and it was very clear that not knowing about the genes and the molecular biology was going to greatly limit us in moving forward. The gamble was, let's move back to a very simple system and hope that what we learn about aging in this simple system applies back to humans. And I think the gamble worked. We did identify what I call the sugar pathway or the PKA or Ras/PKA, and then the protein pathway, the TOR-S6 kinase. "
Research has demonstrated that these initial findings in yeast hold true in other animals as well, including worms, flies, mice and a group of people in Ecuador who have Laron syndrome, a rare genetic disorder where they lack the receptor for growth hormone. As a result, they cannot grow taller than 4 feet.
Interestingly though, this genetic anomaly also appears to protect them against chronic diseases such as diabetes and cancer — even when consuming a less than ideal diet. According to Longo, there's reason to believe the findings apply to most other people as well, as we now know growth hormone and growth hormone receptor in humans regulates both the TOR and MPK pathways.
"We now suspect there is a network pathway starting with the growth hormone and ending with these transcription factors that we described. These are what I call the captains of protection, that are regulated by the food that you eat," Longo says.
Sugar Avoidance and Fasting Are Powerful Longevity Boosters
Longo was one of the first researchers to identify sugar as an aging accelerator and fasting as a process for improving longevity. In 1997, he published a paper showing yeast could be made to live a lot longer when starved. Shortly after that, they discovered the sugar and protein pathways responsible for this phenomenon.
In essence, what he found was that if you knock out both Ras/PKA and something called LCH-9, which is the S6-Kinase gene in yeast, you could obtain up to a fivefold extension in lifespan. As noted by Longo, "It was clear that the effects of fasting were caused in part by shutting down these two pathways." The question was, does the same apply to humans?
To answer this, Longo looked for equivalents to what they'd identified in yeast. Work done by John Kopchick and Andre Barki showed that, in mice, growth hormone deficiency and growth hormone receptor deficiency caused record longevity extension of 40 to 50 percent. They were also far healthier than normal mice. Half of them were completely disease-free at the time of death. As noted by Longo:
"This is very impressive and remarkable. So, we knew that this was true for yeast and this was true for mice, and the Laron [study] was our way to demonstrate that this is also true for people. To summarize, health and longevity are promoted by either a) having low levels of growth hormone, or b) lack of receptors for growth hormone, so it doesn't matter whether you remove growth hormone or the receptor."
