The capacity of our bodies to sense and respond to the ebb and flow of nutrient levels is vital to sustaining life. As we age, our body shifts in how its cells respond to the number of nutrients available.
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The biological definition of aging is the many processes of cellular damage accumulation in the body. These are known in the scientific literature as the Nine Hallmarks of Aging. We’ve covered the first four or primary, hallmarks already: genomic instability, telomere attrition, epigenetic alterations, and loss of proteostasis.
The next three hallmarks of aging are called antagonistic. Their role is to respond to and block the damage caused by the primary hallmarks. Yet, when bodily conditions become chronic and/or aggravated, they end up contributing to cellular damage, and thus accelerated aging.
The fifth hallmark, and first of the antagonistic, is deregulated nutrient-sensing. Our bodies contain complex regulatory mechanisms that measure nutrient scarcity or abundance. This process tells our cells whether to grow or whether to clean up and repair. This is based on the information it gets from hormone and protein signaling pathways.
The body’s balancing act
Metabolism is every biochemical reaction that goes on in your body. It converts food into the energy that sustains life, and there are specific proteins in the body that cause these reactions. When it comes to eating, your body uses a never-ending cycle that breaks down nutrients in food, rebuilds them, and then breaks them down again.
Energy is required for anabolism, or constructive metabolism, which is the process that builds new cells, maintains body tissues, and stores energy for later use. When your body is in an anabolic state, special enzymes separate the smaller molecules in your food, such as amino acids and glucose. These compounds are absorbed into the blood and carried to the cells, where they are either stored in body tissues such as the liver, muscles, and body fat or used for energy.
Energy is released during catabolism, or destructive metabolism, which is the process that generates the energy needed for all other cellular activities, including repair. When your body is in a catabolic state, it breaks down those complex molecules in order to release the energy you need for fuel. This then feeds the cycle that enables anabolism to begin again.
Building it up
We have evolved to be able to transition between anabolic and catabolic states, which 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 blog 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 our blog 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 life spans, 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.
What else can I do?
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More about The Institute for Human Optimization
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