Diet, biological aging, and evolutionary trade-offs: The Twins Nutrition Study

A new study shows reversal of biological aging on a healthy plant-based diet.

In April of last year, I wrote a post called Wholesome plant-based foods – NOT vegan junk food – help you live a longer, healthier life, which discussed a study involving UK Biobank, a cohort study which was established to identify the causes of a wide range of complex diseases of middle and old age. The study found a reduced risk of all-cause mortality, cancer and cardiovascular disease in people who ate the most healthy plant-derived foods, and the fewest unhealthy plant-derived foods and animal foods.

Now, we have a tantalising indication of how a healthy plant-centric diet protects against aging-related disease, with the publication of a study which demonstrated reversal of biological aging in people who were assigned to eat a healthy all-plant diet for just eight weeks... but not in their identical twins who were assigned to eat a healthy omnivorous diet.

TwiNS: a nutrition researcher's dream

The study was part of the Twins Nutrition Study (TwiNS) which formed the subject matter for the Netflix documentary You Are What You Eat: A Twin Experiment. While the documentary tracked the progress of just four twin pairs through the eight-week experiment, the TwiNS project enrolled a total of 44 individuals (22 twin pairs), of whom 21 twin pairs completed all requirements for this study.

To be eligible to participate in the experiment, each twin had to be considered "healthy" by US standards: body mass index (BMI) under 40, LDL-cholesterol level below 4.9 mmol/L (190 mg/dL), and not suffering from uncontrolled hypertension, metabolic disease or diabetes. That's a pretty low bar for "healthy", but if was set any higher, the researchers may not have found enough eligible participants!

16 sets of twins were female, the average age of participants was 40, average BMI was 26.9 (overweight but not obese), and blood pressure averaged 124/75. The study group included twin pairs of Asian, Black/African American, Native Hawaiian/Pacific Islander, White and multiracial ethnicities.

Blood and stool samples were taken at baseline, four weeks, and at completion of the study, and biometric data such as weight and (for a small subsample of participants) body composition were measured.

One twin from each pair was randomised to follow a healthy omnivorous diet, emphasising minimally processed foods and including 170-225 g (6–8 ounces) of meat, one egg, and one and a half servings of dairy per day; the other twin was assigned to follow a healthy vegan diet, also emphasising minimally processed foods but excluding all animal products. All participants received nutrition education and instructions on how to follow the diet to which they had been assigned, and for the first four weeks of the experiment, participants received home-delivered meals and snacks that conformed to the principles they were being taught. To assess their level of compliance with the diet recommendations, participants logged their food intake on the Cronometer app at baseline, week four, and week eight, and were also contacted randomly to submit 24-hour diet recalls. Comparison of before-and-after food records showed that virtually all participants improved their diet quality, regardless of which eating pattern they were assigned to.

For researchers interested in the impact of dietary changes on health outcomes of people with diverse genetic backgrounds, this study design is a dream come true. Identical twins have identical genes, as they both originate from the same fertilised egg. And since each participant in this experiment had to be reasonably metabolically healthy, any divergence in health outcomes between twins assigned to vegan vs omnivorous diets, could reliably be attributed to the effects of those different dietary patterns rather than to random genetic or environmental factors.

A previous paper, published last November, analysed the cardiometabolic impact of the two healthy diet patterns and found that twins assigned to the vegan diet had lost two kilograms more weight, and lowered their fasting insulin and LDL-C significantly more than their omnivorous twins.

Assessing biological aging

For the biological aging study, researchers compared patterns of DNA methylation in blood samples taken at baseline and after eight weeks on the assigned diet. DNA methylation is a form of epigenetic modification - that is, it alters the expression of genes without altering the genes themselves. As you may remember from high school biology class, genes are segments of DNA. DNA is comprised of nucleotides which spell out an amino acid sequence that codes for structural and regulatory proteins. Since we don't want all of our genes to be ordering the construction of all of the proteins for which they code, all the time, our bodies use methylation to control the 'switching on' and 'switching off' of genes. Methylation of DNA typically represses the expression of genes, effectively locking them in the 'off' position.

Previous research has found that increased DNA methylation levels are associated with aging. A number of 'epigenetic clocks' have been developed, using blood and tissue samples from both healthy and sick people. These clocks have been refined over time with new data, and are now able to estimate biological age and predict age-related outcomes with high sensitivity and reliability.

Telomere clocks have also been developed, that estimate biological age based on the length of the protective 'caps' on the end of chromosomes. These telomeres shorten with each cell division until cells become senescent - that is, they can no longer replicate. The accumulation of senescent cells, which stimulate the release of inflammatory compounds, is a hallmark of aging and aging-associated diseases such as cancer and atherosclerotic heart disease.

This study used a total of nine first-, second- and third-generation epigenetic clocks, as well as calculating the individual epigenetic ages of 11 organ systems (Heart, Lung, Kidney, Liver, Brain, Immune, Inflammatory, Blood, Musculoskeletal, Hormone, and Metabolic), and a composite system age.

Compared to baseline measurements, the twins assigned to the healthy vegan diet had significant decreases in three of the epigenetic age metrics, the composite systems age metric, and five out of 11 systems: Inflammation, Heart, Hormone, Liver, and Metabolic. There were no significant changes in any epigenetic clock measures in the twins assigned to the healthy omnivorous diet. Average telomere length was significantly longer at week eight than at week zero for the twins who went vegan, but not for their omnivorous siblings.

In summary, twins assigned to the healthy vegan diet pattern became biologically younger, as assessed by multiple metrics, after just eight weeks of excluding animal products from their diets.

Plenty of caveats apply. The study population was small, the study duration was short, and not all the epigenetic clocks showed reversal of biological aging. But it's astonishing that any change in biological age was demonstrable after just eight weeks! In fact, the principal investigator of the study, veteran nutrition researcher Christopher Gardner, was reluctant to include epigenetic age measures because he did not believe that any marker of aging could change over such a short duration (commence at 8:27):

Before anyone could confidently claim that a healthy plant-exclusive diet reverses biological aging, this study would need to be replicated in a much larger group of participants, and over a considerably longer time period.

Implications of this study... and a hypothesis

With those caveats acknowledged, the results are intriguing enough to prompt me to speculate about what they might mean. Animal products are rich in many important nutrients, including protein, several of the B vitamins, and bioavailable iron and zinc. Especially in economically underdeveloped regions with marginal food intake and reliance on low-nutrient-density starchy staple foods such as plantain and manioc, limited availability of animal products can put people at risk of malnutrition - especially children and pregnant women. So why would intake of animal products, which have played a significant role in the human diet since our species first emerged, accelerate the aging process?

Christopher Gardner stresses that he doesn't know, and wonders whether DNA-damaging byproducts of dry-heat meat cooking methods could be to blame. There's also evidence that intake of dietary advanced glycation end-products (AGEs), which very literally accelerate biological aging, is lower on a vegan diet than on the plant-rich but not plant-exclusive Mediterranean diet. But I suspect the answer might be much more profound: namely, that consumption of animal products is a type of evolutionary trade-off.

An evolutionary trade-off is a situation in which fitness (reproductive success in a given environment) of one trait increases at the cost of decreased fitness in another trait. Selection pressure is an evolutionary force that causes a particular characteristic to be more favourable to gene survival in certain environmental conditions. If a preference for animal food consumption caused a prehistoric woman with a marginal food intake to be more likely to carry her pregnancies to term, and more of her progeny to survive to reproductive age, this would exert powerful positive selection pressure that would not be offset by a negative effect of animal food consumption on her own longevity. From an evolutionary point of view, you're more 'fit' if you have 15 babies, 10 of whom survive to reproductive age, before dying in your late 40s just as your reproductive capacity is ebbing away anyway, than if you have five surviving offspring and live to a ripe old age in robust health. You, as a 21st century individual with control of your fertility, might have a very different set of priorities, but the genes that shape your behaviour haven't caught up to modern times!

What I'm saying is essentially that our ancestors' ability to make increasing use of animal products (especially after the taming of fire) may have increased the number of their offspring that survived to reproductive age, and hence to the success of our species, but at the cost of reduced individual lifespan and healthspan.

Compare my hypothesis with one of the principal theories of aging: antagonistic pleiotropy, which was proposed in 1957 by the evolutionary biologist George Williams. This hypothesis suggests that certain gene variants confer beneficial effects early in life by enhancing reproductive success, while also causing detrimental effects later in life by contributing to the aging process. Antagonistic pleiotropy has been demonstrated in a number of species, including humans.

My argument is that humans have a cultural (rather than genetic) inheritance of preference for animal product consumption, which was beneficial in our species' development when foods were seasonal and often scarce, infant mortality was high, and a minority made it past middle-age. But now that most of the causes of premature mortality have been defeated, our taste for animal-derived foods might be detrimental to the goal of maximising healthy lifespan.

Given the tremendous physiological reserve that we're all born with, accelerated aging may be taking place at an epigenetic level, while on the outside, the individual appears fit and well for many decades... until they suddenly and unexpectedly succumb to an aging-related disease. Are all those buff-looking carnivore influencers accelerating their biological aging, and putting themselves at heightened risk of aging-related diseases, by eating nothing but animal products? Maybe they can be persuaded to donate blood samples for epigenetic analysis, so we can find out!

What should I eat?

It's astonishing just how many books and magazine articles and blog posts have been written, how many documentaries made, how many podcasts recorded, and how much online video content produced, in an attempt to answer the deceptively simple question, 'What should I eat?' And of course, the number of scientific articles published on this topic is practically uncountable.

The food choices of our ancient ancestors were primarily shaped by two factors: availability and taboos. The former factor imposes self-evident limits; if it’s not there, you can’t eat it. The latter has been observed to sharply delimit consumption of available plants, animals and insects in every human society studied so far, with the rationale frequently embedded in the spiritual rather than physiological or practical realm. Preference played a distinctly subordinate role; no matter how much an individual enjoyed eating one particular food, if that item was out of season or forbidden on the basis of sex, social class, life stage, health status (e.g. sickness, pregnancy or menstruation), religious observance or general prohibition, then it was off the menu.

We now live in an era in which, at least in the affluent West, an abundance of food is available all year round, and only a small fraction of the population adheres to religious dietary prescriptions... although a convincing argument can be made that the relatively small number of animal species consumed in most Western countries, and the disgust that is almost universally evinced toward eating - for instance - insects, dogs or horses, all of which are relished in many other cultures, is evidence that taboo is still a potent influence on our food choices.

Today, among those with sufficient economic means to afford them choice in what they consume, the two factors with the greatest influence on food choice are preference - what do I like to eat? - and perception of healthfulness - what do I believe is healthiest for me to eat? At least in Western countries with diversified food supplies, it's no longer particularly challenging to put together an entirely plant-based diet that is not only delicious, but meets practically all nutritional requirements at every life stage.¹ For the first time in human history, it may be possible to optimise our diets both for our desired level of reproductive success in earlier adult life, and for healthy longevity - that is, remaining biologically younger than our chronological age throughout life, so that we slash our risk of aging-related disease and compress terminal decline into our final days or weeks, rather than slowly dying for the last few decades of our lives as is now more common than not.

As every scientific paper always stresses at the end, more research is required to test this hypothesis! But it is supported by previous research, including the UK Biobank study, and there is no contradictory research (i.e. research indicating that decreasing intake of plant foods or increasing intake of animal foods is associated with longer healthspan or lifespan). It’s no coincidence that millionaire biohacker Bryan Johnson, who is pouring his considerable financial resources into reversing his biological age to 18, follows a plant-exclusive diet. In the mean time, while we wait for confirmatory research, you can't go wrong by adding more fruits, vegetables, legumes, whole grains, nuts, seeds, herbs and spices to your diet.

For information on my private practice, please visit Empower Total Health. I am a Certified Lifestyle Medicine Practitioner, with an ND, GDCouns, BHSc(Hons) and Fellowship of the Australasian Society of Lifestyle Medicine.

1. Vitamin B12 is the only nutrient that is considered essential to supplement in an entirely plant-based (vegan) diet. Supplementation with long-chain omega-3 fats (DHA and EPA) from microalgae may also be advisable, particularly in pregnant women, children, and older adults.