WARNING: Is Your Body's Nutrient Detector Unknowingly Broken? – Part 2
Dear Longevity Insider,
We have evolved to be able to transition between anabolic and catabolic states.
This has allowed us to survive and grow in environments in which nutrient availability is variable. One of the ways that our bodies do this is a signaling pathway controlled by a protein kinase, or enzyme, called mTOR.
mTOR controls cell growth, movement, and survival, as well as protein synthesis, autophagy, and transcription (how a cell copies its information when it’s ready to divide). It is adaptable and coordinates cell activity based on cues from the environment, such as nutrients, or lack thereof, and growth factors. It is ultimately responsible for the sensing of high amino acids concentrations.
Insulin-like growth factor-1 (IGF-1) primarily works with growth hormones to promote development in bone and tissues. IGF-1 uses the same signaling pathway as insulin, which tells the cells that glucose is present. This is known as the “insulin and IGF-1 signaling” (IIS) pathway, which is the most conserved age-controlling pathway throughout evolution. The IIS pathway regulates metabolism, growth, tissue maintenance, and reproduction in response to nutrient abundance.
When nutrients are abundant, the mTOR and IIS pathways work in tandem to form a network that helps to keep the body in an anabolic state that promotes cell growth and building. Conversely, mTOR is inhibited when nutrients are limited, which puts the body in a catabolic state and allows for cellular clean-up and repair.
Breaking it down
You may remember from a former article that adenosine monophosphate-activated protein kinase (AMPK) acts like the body’s cellular housekeeper. It is what inhibits mTOR to promote catabolism. AMPK senses low energy states by detecting high AMP levels. AMP (adenosine monophosphate) is the end product of energy production.
Sirtuins are a family of proteins that regulate cellular health and they’re made by almost every cell in the body. They only function properly in the presence of nicotinamide adenine dinucleotide (NAD+), which is an essential cofactor in the production of energy by the mitochondria inside the cell and in energy metabolism.
Together, AMPK and sirtuins signal nutrient scarcity and catabolism. AMPK boosts NAD+, which in turn activates sirtuins. This initiates autophagy and the cellular housekeeping process begins.
You are what you do AND don’t eat
Sirtuins, mTOR, and the IIS pathway are all connected and respond to nutrient availability. One major way is via AMPK, and when it is activated, it prompts a cascade of complex interactions. Their functions fluctuate depending on the metabolic state of our body at any given time, thus their being labeled as part of the antagonistic hallmark of aging: deregulated nutrient-sensing.
Lopez-Ortiz et al concluded in their landmark paper, The Hallmarks of Aging, “Collectively, current available evidence strongly supports the idea that anabolic signaling accelerates aging, and decreased nutrient signaling extends longevity.”
Dietary restriction (DR), such as intermittent fasting or the fasting-mimicking diet, is the only intervention that has consistently been shown to increase lifespan. While we are still learning exactly why and how this is the case, the above-referenced research is showing that the sensing of nutrients plays an important part. We know that part of the reason dietary restriction works is by obstructing mTOR and the IIS pathway and activating AMPK and therefore sirtuins.
In a previous article on autophagy, we explained that intermittent fasting means becoming conscious of the times you choose to eat and increasing the time you’re not consuming calories. It is also known as time-restricted eating. Valter Longo, Director of the Longevity Research Institute, helped popularize what he calls the fasting-mimicking diet. His research showed that mice that fasted intermittently had improved lifespans, reduced inflammation, increased cognitive ability, and that this mechanism could be used in humans for similar results.
Dietary restriction is an effective way to increase your lifespan and your healthspan. It has been proven, and while it takes a lifestyle adjustment, it is possible for your choices to have a direct impact on how you age.
To your longevity,
Anil Bajnath MD
CEO/Founder, Institute for Human Optimization
Chief Medical Officer, Longevity Insider HQ