Unlock Longevity: The Power of Exercise & Gene Expression

Valerie Rider
Apr 17
4 min read

Some people read fiction before bed. I have been reading Outlive by Dr. Peter Attia. My husband calls it a textbook, but I am thoroughly entertained. It has inspired ideas about health, fitness, and my own vision for what Dr. Attia refers to as the “marginal decade.”

Obviously, fitness takes a massive role in my life, but that hasn't always been the case.

I'm passionate about fitness because I know what being unfit feels like. I remember a time when I often encountered doors that were difficult to open, bags and boxes that were hard to carry, and activities that were challenging to do. Today, with a strong body, a good working heart, and decent lung capacity, I rarely think, "Am I going to be able to do that?" Instead, the question I ask is only, "Do I want to do that?"

You can train for anything; longevity is no different. It's not about living long, but about how you want to live in your later years. There is a more capable you waiting, and I can't wait for you to meet them.

Research Round-Up to Inspire You to MOVE

I explored two studies recently that I want to share with you.

1 Leisure Time Physical Activity Of Moderate To Vigorous Intensity And Mortality: A Large Pooled Cohort Analysis

This large-scale analysis combined data from over 650,000 adults to understand how leisure-time physical activity impacts life expectancy. It was an observational study, so it's hard to “prove” actual causation, but the correlation is interesting. Specifically, this caught my eye because we often think thin equals healthy.

According to this study, that's not everything.

📊 Any Activity Helps:

Even low levels of physical activity (such as brisk walking for up to 75 minutes per week) were linked to gaining about 1.8 additional years of life compared to no activity.

📊 More Activity, More Benefits:

Meeting recommended activity levels (about 150–299 minutes of brisk walking weekly) was associated with gaining roughly 3.4 years of extra life. Those exceeding this level saw even more significant benefits—up to 4.5 additional years.

Some is better than none. Even 10 minutes a day helps.
Hitting the guidelines (150 min/week) is a significant turning point for longevity.
Double it (~300 min/week) for even more years gained, though the benefits taper off after that.

📊 Body Weight Matters, But Movement Counts More:

Physically active individuals live longer regardless of body weight. Interestingly, active individuals who were overweight or mildly obese lived longer than inactive individuals with a normal weight.

Active + Normal Weight = Longest life
But… active + obese (class I) outlived inactive + normal weight
Biggest loss: Inactive + Obese Class II = 7.2 years lost

📊 Most Significant Gains for Those at Higher Risk:

Individuals who smoked previously or had a history of heart disease or cancer saw the most significant increases in life expectancy from regular physical activity.

Former smokers (+5.5 years)
People with heart disease or cancer (+6–7 years)

🏃‍♀️ Practical Takeaways:

Even modest increases in physical activity can significantly improve your longevity.
Consistency matters more than intensity—regular activity is key.
Moving more can offset risks associated with higher body weight.

🧠 Limitations:

Self-reported data: Participants might inaccurately recall their activity levels.
No strength training data: Did not assess potential benefits of strength or resistance exercises.
Limited diversity: Participants were primarily white, limiting broader applicability.
Moderate follow-up length: About 10 years; may not reflect long-term outcomes.
Observational study: It can't be proven that physical activity directly causes longer life expectancy. Other lifestyle factors could influence results. For example, do people that exercise eat better, manage their stress better, prioritze sleep more? Is exercise causing increased life span or is it another factor? Anecdotaly, exercise is the lowest barrier. Get consistent with that and other health supporting activities tend to domino.

Moore SC, Patel AV, Matthews CE, Berrington de Gonzalez A, Park Y, Katki HA, Linet MS, Weiderpass E, Visvanathan K, Helzlsouer KJ, Thun M, Gapstur SM, Hartge P, Lee IM. Leisure time physical activity of moderate to vigorous intensity and mortality: a large pooled cohort analysis. PLoS Med. 2012;9(11):e1001335. doi: 10.1371/journal.pmed.1001335. Epub 2012 Nov 6. PMID: 23139642; PMCID: PMC3491006. https://pubmed.ncbi.nlm.nih.gov/23139642/

2 The Impact Of Exercise on Gene Regulation in Association with Complex Trait Genetics

So often we see genes as fixed and something we can't change, but that isn't completely true. Although you cannot alter your genetic makeup, you can dial up or dial down the expression of these genes with the potent application of exercise. The researchers aimed to map how endurance exercise influences gene expression across multiple tissues and how those changes might reduce the risk for complex diseases (such as heart disease, high cholesterol, asthma, etc.).

🧬 Exercise Changes Genes Across Many Tissues:

The study examined gene changes in 15 different tissues after endurance training. Most genes were uniquely impacted in specific tissues, highlighting targeted benefits.

78% of genes that responded to training were unique to a single tissue.
The muscles, heart, liver, and spleen showed the strongest and most diverse responses.
Blood and spleen tissues, in particular, showed strong overlap between exercise-induced changes and genes linked to immune and metabolic disease risk.

🧬 Exercise Can Overcome Genetic Variability:

Gene changes from exercise were strong enough to surpass natural genetic variations, suggesting exercise has a powerful influence on gene expression related to health.

Example: Exercise significantly changed APOB, a key gene in cholesterol metabolism, in colon and lung tissue.

🧬 Exercise Influences Disease-Related Genes:

Genes linked to conditions such as high cholesterol, asthma, and obesity were notably affected by regular exercise, suggesting potential disease mitigation.

🏃‍♀️ Practical Takeaways:

Exercise significantly impacts gene expression, potentially reducing the risk of complex diseases.
Regular endurance exercise can strongly influence health outcomes, even beyond genetic predispositions.
Benefits of exercise extend across multiple body systems, indicating its broad role in maintaining health.

🧠 Limitations:

Animal model: Findings are primarily based on rat studies, so human application needs careful interpretation.
Limited genetic diversity: Human genetic data mainly from European populations.
Complexity: The multi-tissue approach, while comprehensive, adds layers of complexity in interpreting results.
Observational correlations: Direct causation of gene-disease relationships remains challenging to confirm.

Vetr, N.G., Gay, N.R., MoTrPAC Study Group. et al. The impact of exercise on gene regulation in association with complex trait genetics. Nat Commun 15, 3346 (2024). https://doi.org/10.1038/s41467-024-45966-w