Grant was out for his weekly hill ride with his old mate Stephen. Stephen was now in his nineties and Grant just about to turn 90. The day was sunny and warm. At halfway, they stopped and had a coffee and talked about their grandchildren, each showing off a bit to the other. On the last high hill Grant took off and lead out a sprint. It was all good until just as they hit the top, Grant felt a sudden pain in his chest and dropped dead. Stephen, after a lifetime of never quite winning the hill sprints, seeing him falter took his chance and rode past him – at the exact moment he finally won a sprint, he too felt a sudden pain and dropped dead.
Neither man even had the chance to pull over and unclip from their carbon racing bikes. They lay turtle up, each having won the final sprint to the line.
As Mark Sisson puts it, “they lived long and dropped dead”. Good quantity and great quality.
Anyway, that’s my little fantasy and thought experiment about how I should die along with my long time mate Stephen Farrell, who strangely thrashes me at everything except hill climbs.
Two things are inevitable in life, death and taxes.
I’m here to talk about the first one. I am assuming we want both quantity and quality of life. How do you get the most “bang for your buck” so to speak? The first clue might be in the caloric restriction data – eat less live longer. Sounds feasible, and some data support this idea. The unappealing thing, to me at least, is that eating is fun, enjoyable, and perhaps in the end the trade off isn’t worth it because you are alive but had to go hungry the whole time so life was just way less fun. But there are new data and new hypotheses about how glucose metabolism may be the driver, not caloric restriction.
How glucose metabolism fits in
I want to spend the main part of this blog summarizing (at least as well I can summarize a complex neurophysiology paper) how glucose metabolism controls the aging process, mainly through the brain. I’m talking about a paper just published in Trends in Endocrinlogy and Metabolism called “Metabolic mystery: aging, obesity, diabetes, and the ventromedial hypothalamus” available here. First, its hardly light bedtime reading, unless you quickly want to fall asleep. Second, there is so much complex genetics, animal study material, and hormonal and neuronal mechanistic stuff it takes a very long time to get through it. So I’ll spare you all the challenge and get straight to the major hypotheses and practical implications.
They start by revisiting the well known phenomenon that caloric restriction can increase lifespan, in at least some animals. Possibly humans and primates, although the jury is still out on that, and the only decent primate study wasn’t a decent study after all because of the high sugar diets for both caloric restriction and ad lib feeding groups.
Major findings of this review
- The energy mediating centre in the brain (the ventromedial hypothalamus) has specific glucose and FFA (free fatty acid) sensors.
- These sensors directly affect hepatic (liver) and peripheral (muscle and organ) glucose metabolism in opposite ways.
- High glucose in the blood drives a decrease in liver glucose production and an increase in glucose metabolism in other tissues. It’s vice versa for lower glucose and increased FFAs in the blood.
- Increased oxidation of glucose in peripheral tissues requires less oxygen to metabolise but results in more oxidative stress (i.e. damage) to the tissues. This damage is directly implicated in aging. Increased availability of insulin and insulin-like growth factor 1 (IGF-1) are also implicated in this process.
- Glucose on its own may not be enough. Increased mortality of Type 2 diabetics who are aggressively treated with exogenous insulin is evidence for this.
- Take home message – there is direct evidence that high dietary glucose load (read CARBOHYDRATE)
triggers the mechanisms that directly accelerate aging. Fatty acids on the over hand do much less damage.
- My extra interpretation of the field and other papers beyond these guys: One reason dietary restriction works is because it reduces the carb load. Another way of achieving the same effect without hunger might be to….eat less carbs, and more fat!
Here’s the abstract:
We propose that energy balance, glucose homeostasis, and aging are all regulated largely by the same nutrient-sensing neurons in the ventromedial hypothalamus (VMH). Although the central role of these neurons in regulating energy balance is clear, their role in regulating glucose homeostasis has only recently become more clear. This latter function may be most relevant to aging and lifespan by controlling the rate of glucose metabolism. Specifically, glucose-sensing neurons in VMH promote peripheral glucose metabolism, and dietary restriction, by reducing glucose metabolism in these neurons, reduces glucose metabolism of the rest of the body, thereby increasing lifespan. Here we discuss recent studies demonstrating the key role of hypothalamic neurons in driving aging and age-related diseases.