Longevity science has been a popular topic in the past couple of years, largely due to a classic book called Lifespan by Harvard professor and longevity researcher David Sinclair, PhD.
In his book, Sinclair clearly outlines what science knows today about why we age, and what we can do about it. Yes, there are things we can do to delay aging on the level of our DNA.
Let's look at how exercise and in particular strength training affect your longevity epigenome (a system in your genome that regulates which DNA segments get expressed and which stay silent), in three important areas.
1. Sirtuin genes: Once activated, they produce enzymes that defend organisms from chronic diseases, and prolong both health- and lifespan. These genes respond to adversity in the environment (i.e., a state of stress) by hunkering down cell division and growth and making sure we survive until things get better before we start replicating (on a cellular level) again.
These sirtuin genes need a metabolic molecule, nicotinamide adenine dinucleotide (NAD), to get activated. Without NADs, we wouldn't survive even a few seconds. What scientists also discovered relatively recently is that our levels of NAD get lower with age. A 50 year old will have half the NAD levels of a 20 year old, for example. That means sirtuin activity goes down with age. There are several ways we can raise our levels of NAD and activate the sirtuin genes: we can mimic adversity with certain supplements, or do it naturally via intensive exercise or caloric restriction.
The authors of the classic Body by Science book have stated that optimal health can be achieved when we maintain a proper balance between our anabolic (growth) and catabolic (adversity) states. The most recent research on longevity certainly seems to support this notion.
For example, when scientists measured people's biological clocks, they showed that elite athletes tend to be biologically older than their peers. These are people who spend too much time in the catabolic state and not enough in the recovery, anabolic state.
The opposite is true for "couch potatoes," who spend most of their time in an anabolic state, which leads to the accumulation of body fat, an increase in chronic inflammation, a loss of lean muscle tissue due to disuse, inhibited metabolic health overall, and faster aging.
So what is needed is the right amount of catabolic stimulus, followed by the right amount of anabolic recovery. Look at it as medicine: if you take too much of it, it gets toxic for the body; take too little, and it doesn't do anything. Take the right dose and it works.
In a November 2020 Experimental Gerontology paper, scientists demonstrated that strength training activates 3 of our sirtuin genes-SIRT1, SIRT3, and SIRT6-while also raising levels of the telomerase enzyme, which lengthens our telomeres (one of the markers of aging).
This is in line with a 2007 paper where scientists saw a reversal in the expression of the markers of DNA aging after a group of older people performed strength training for 6 months.
2. AMPK is a metabolite control enzyme that, when activated, stimulates energy-generating processes, such as glucose uptake (so the carbs/sugars we eat go to our muscle) and fatty acid oxidation (burning fat), and decreases energy-consuming processes, such as protein and lipid synthesis (increase in muscle and fat tissue). It gets activated by low energy levels and by exercise, and it also restores the function of mitochondria (energy-producing factories located inside our cells).
3. mTOR senses nutrition. When activated, it triggers an anabolic state and leads to tissue growth (e.g., muscle and fat synthesis). We activate mTOR by strength training (a good thing in the short run), or consuming amino acids (particularly leucine) and carbohydrates (this is why bodybuilders have protein shakes with carbs after their workouts). When there is a lack of amino acids or carbohydrates, mTOR signals cells in stress to hunker down and divide less; it improves survival by boosting DNA repair, reducing inflammation caused by senescent cells (also called zombie cells), and allowing cells to digest old proteins.
We should add that people who need to increase their lean muscle tissue should probably focus on activating mTOR, particularly 24-48 hours after the strength training workout, more than downregulating it.
"Sirtuins, mTOR, and AMPK evolved to protect the body during times of adversity by activating survival mechanisms. When they are activated . . . organisms become healthier, disease-resistant, and longer lived," Sincalir writes.
"The longevity regulators AMPK, mTOR, and sirtuins are all modulated in the right direction by exercise, irrespective of caloric intake, building new blood vessels, improving heart and lung health, making people stronger, and, yes, extending telomeres."
In addition to these pathways, Sinclair outlines 9 main hallmarks that scientists associate with aging:
Genomic instability caused by DNA damage
Shortening of our telomere lengths (telomeres are caps located at the end of our chromosomes to prevent DNA damage when cells divide, and they get shorter with each cell division)
Changes to our epigenome that control which genes are turned on or off
Loss of healthy protein maintenance (i.e, proteostasis)
Deregulated nutrient sensing
Mitochondrial dysfunction
Accumulation of senescent (zombie) cells
Exhaustion of stem cells
Altered intercellular communication and the production of inflammatory molecules
In a 2018 Frontiers in Endocrinology review paper, scientists demonstrated that exercise positively affects not just one or two, but ALL of the above 9 hallmarks of aging!!!
The scientists stated,
"Exercise should be seen as a polypill, which improves the health-related quality of life and functional capabilities while mitigating physiological changes and comorbidities associated with aging."
What is exercise for longevity?
Since exercise is one of the means to activate these longevity pathways, let's look at what exercise actually is.
Our favorite definition of exercise is the one offered by Doug McGuff and John Little in Body by Science: "a specific activity that stimulates a positive physiological adaptation that serves to enhance fitness and health and does not undermine the latter in the process of enhancing the former."
If you are familiar with the NET method, you can clearly see how it fits this definition. It is specific, as it is performed for the purpose of increasing our strength and metabolic and general health. It is an intense enough stimulus that will lead to positive physiological adaptations. It will enhance your fitness, and it won't undermine your health, as it is one of the safest ways to exercise, productively.
By this token, other so-called exercises are simply "physical activities" (and let us be clear: physical activity is very important!), since they don't meet all the criteria of the above definition. Some are even dangerous, and they may undermine your health (if you do too much, or compromise the health of your joints by using improper form or explosive movements).
The science is clear: proper exercise is the most effective anti-aging medicine we know today!