Newsletter #313: Biological Age & Muscular Strength 🧬
Hey y’all! This week, we would like to revisit the topic of biological age.
Age is normally defined chronologically, in terms of how many years one has been alive. Time marches on inexorably, and there is nothing you can do about chronological age.
But on an intuitive level, all of us know that age is not merely a number.
For instance, I’m sure that you realize that two 40-year-old humans can often look and perform very differently from an average individual of the same birth cohort. Like, one might seem more like a 30-year-old, while the other could more closely resemble a 50-year-old. One might speculate that if you examined each of them under a microscope, you’d see that their cells and tissues diverge significantly from their chronological age.
And indeed, new biological age testing seems to bear this out, through examining epigenetic modifications. Essentially, most of these tests are looking at molecular “tags” known as methyl groups, which are affixed to DNA and alter the expression of genes to which they are in close proximity. DNA methylation changes in relatively predictable ways in response to certain stressors and through the aging process, and these modifications have been found to be associated with development of age-related diseases as well as predictive of mortality.
This is intriguing from a strictly diagnostic perspective, since these epigenetic biomarkers can serve as surrogate markers of aging at the cellular level, and can assess how rapidly an individual is aging compared to the rate attributable to the passage of time. If you learn that you are aging at a faster rate than average, you might be able to undertake lifestyle and medical interventions to reverse course. But it’s also exciting because although we can do little about the genome itself, epigenetic modifications are theoretically reversible. The most important distinction between chronological aging and biological aging is that the latter is actionable — you can do something about it!
To gain more insight into the promise of biological age testing, Dan spoke with Hannah Went on the podcast this week, which we’re delighted to share with you today. We also went ahead and dug into a recent study exploring the relationship between muscular strength and biological age acceleration, a topic which should be relevant to every single one of us.
New humanOS Content
humanOS Radio: Testing Biological Age and the Pace of Aging. Podcast with Hannah Went.
In this episode of humanOS Radio, we welcome Hannah Went, a visionary in the realm of longevity and disruptive health technologies. Hannah is the founder of TruDiagnostic, a cutting-edge company specializing in methylation array-based diagnostics for life extension and preventive healthcare. Today, TruDiagnostic serves functional medicine providers worldwide and boasts one of the largest private epigenetic health databases, with over 75,000 patients tested.
Driven by a commitment to research, under Hannah’s leadership, TruDiagnostic has spearheaded over 30 clinical trials exploring the epigenetic methylation changes in longevity and health interventions. Additionally, she shares her wealth of knowledge through Everything Epigenetics, offering valuable insights into how DNA regulation impacts health.
In this podcast, we explore the future of longevity, the power of epigenetics, and the transformative potential of innovative healthcare technologies.
This Week’s Research Highlight
Lower muscular strength is associated with biological age acceleration.
Muscular strength has emerged as a powerful predictor of mortality, even exceeding muscle mass. To that end, measuring grip strength via a dynamometer has been validated as a reasonably reliable proxy for total body strength, and has the added advantages of being both efficient and inexpensive.
In a prior study, epigenetic clocks were found to be linked to frailty in a cohort of elderly adults who were followed for three years. To examine how muscular strength correlates with biological aging over a longer timespan, researchers at the University of Michigan analyzed data from 1,275 participants from the Health and Retirement Study — the longest running longitudinal study of older adults in the United States.
Subjects had provided a range of physical and chemical measurements every four years, including blood samples as well as tested hand grip strength, the latter of which was normalized to body mass.
Blood samples were analyzed for three different epigenetic clocks, each of which looks at biological age in a slightly different way (check out the podcast for a little more info on how these tests work):
- PhenoAge: Trained using clinical biomarkers (serum glucose, CRP, etc) to estimate phenotypic age, which has been shown to predict morbidity and mortality.
- GrimAge: Analyzes DNA methylation to estimate lifespan — more accurately than calendar age.
- DunedinPoAm: Estimates the pace of biological aging, relative to chronological time.
First, the researchers looked at cross-sectional data from participants in the same year, to see how relative grip strength was associated with epigenetic age at that moment, similar to previous research.
But the great strength of this study is the subjects were followed for 8-10 years, with multiple measurements taken over that timespan. Thus, the researchers were able to compare measurements in grip strength from baseline to later follow-up, and see how this was linked with epigenetic age as well as the rate of aging. In this way, the scientists could model how changes in strength over time were linked to subsequent DNAm age acceleration.
Sure enough, the researchers found that lower relative grip strength was independently associated with DNAm age acceleration across multiple clocks, although the relationships varied to some degree by gender.
Importantly, this association remained after controlling for sociodemographic factors, and for smoking. Smoking is obviously a well-established risk factor for health outcomes, but it also strongly predicts patterns of DNA methylation, so that's a key confounding factor to take into account when looking at epigenetic aging.
This study was not designed to elucidate underlying mechanisms that would connect weaker grip strength with biological aging, but it's not hard to come up with some possible explanations. The researchers suggest that low-grade systemic inflammation, which drives chronic diseases and mortality in the elderly and has also been implicated in age-related sarcopenia, could be a key mediator. And of course, muscle weakness leads to functional impairments which could make it harder to maintain an array of health-promoting behaviors.
In any case, the link between strength and longevity is impossible to dispute, based on decades of evidence.
For instance, middle-aged men whose grip strength fell in the lower half of their cohort had a more than 2-fold greater risk of dying within a 6-year period, compared to counterparts in the upper half. Another larger study, examining data from more than a hundred thousand people around the world, found that grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure.
Truly, only the strong survive.
Random Trivia & Weird News
🤬 Swearing has been shown to acutely boost grip strength.
In a recent experiment exploring "beneficial effects of swearing," researchers found that when participants repeated a swear word, their hand grip strength increased by a mean of ~5.5 pounds, compared to speaking a neutral word.
Prior investigation suggests that cursing has this effect through disinhibition. Basically, we are naturally inclined to limit behaviors that are likely to lead to pain or discomfort (in this case, squeezing a dynamometer with your fingers as hard as possible). This tendency no doubt evolved to shield us from injury, but also make it difficult for us to realize our true physical potential. Apparently foul language helps us cut through these neural brakes.
Podcasts We Loved This Week
- Yaakov Stern: Cognitive reserve and individual differences in brain aging and Alzheimer’s risk. Via Brain Ponderings with Mark Mattson.
- Aarathi Prasad: The 4,000-year history of humans and silk. Via Science Friday.
Products We Like
GLYLO
Another key driver of the aging process is accumulation of advanced glycation end products (aptly known as AGEs). Pankaj Kapahi from the Buck Institute spent years screening for compounds that could reduce glycation, and the result was this product. Interestingly, his testing also found that GLYLO caused rodents to eat less and subsequently lose weight. If you struggle with your appetite, or just want to increase lifespan and healthspan by blocking AGEs, this is worth a shot.
humanOS Catalog Feature of the Week
Stress & Resilience
This week, we’d like to highlight our course on Stress and Resilience, from our Daily Performance Program. Stress is a state of mental strain resulting from demanding circumstances. But, stress is not merely in your head — it is a real phenomenon with measurable biological effects.
Nevertheless, it’s worth noting that stress isn’t a wholly bad thing. We now know that we actually need a certain amount of stress in order to be healthy and perform at our best, and indeed specific types of stressors (like exercise or polyphenols) appear to have health-promoting effects.
In this course, we break down the different forms of stress, talk about how stress affects cognition, and identify physical stressors that are essential to health. And since psychological stress isn’t entirely avoidable, we also address stress reduction and building resilience, and how to integrate these strategies into your daily life.
Wishing you the best,
