Methionine Metabolism as Fingerprint of Extreme Longevity?
By: Gunnar De Winter
Tags: Health, Food, Aging, Biology, Science

Methionine Metabolism as Fingerprint of Extreme Longevity?

(Pixabay, ar130405)

To study old age

In previous posts, we dove into various methods that are currently being pursued to mitigate the effects of senescence, from blood dilution over drugs and supplements, to stem cells.

(Of course, this is not to say that lifestyle, exercise, diet, genetics, and environment are irrelevant. Quite the opposite, paying attention to these factors is, at the moment, probably our best bet to age healthily.)

However, as noted in our explorations of these interventions, the results that are touted in the media and spur our imagination are more often than not achieved in mice or other model organisms. And if there are human studies, these assess the efficacy of an intervention through biomarkers — which may or may not truly reflect various aspects of the aging process. (Finding very accurate biomarkers of aging is still a work in progress, see for example the recent work on ‘aging clocks’.)

To get human data we would ideally run 50+ year randomized controlled trials in large groups and different populations. Good luck getting funding for that.

We do have another old ace up our sleeve, though. Healthy centenarians, people who reach the age of 100 in relatively good health. Perhaps they can offer us some clues.

A Blue Zones interlude

If you are interested in aging research, you will have heard of the Blue Zones. These zones are places that are demographic outliers. More concretely, in these regions people have a roughly ten time higher chance of becoming a healthy centenarian.

The Blue Zones (source: World Economic Forum)

I emphasize the word healthy, because what we should really focus on is healthspan instead of lifespan. Breaking the human longevity record (122 years) loses its appeal if you are bedridden and in constant pain since your seventies…

These Blue Zones are spread over the world and across cultures, but the people living there do share some commonalities (and I’ll summarize):

Move. Not HIIT training, but move gently throughout the day. Or, to rephrase: don’t sit on your behind all day.

Eat mostly plants, and don’t overdo it on the calories. Include legumes.

Have a purpose, a reason to wake up. It doesn’t have to be a grand goal, but something that gives you ‘drive’.

Don’t stress.

Be engaged. Family, social life…

Lifestyle, remember?

At the current state of knowledge and with the currently available biochemical options, these five factors are some of the best things to keep in mind if you want to increase your odds of aging in good health.

Methionine metabolism

Back to our main story. The Blue Zone recommendations are good, but they’re not a panacea. There are people who live very healthily and still will not make it to 100 (even setting aside issues like disease, accidents, and so on). Vice versa, there are people who dance into their tenth decade while eating bacon and smoking cigarettes.

This implies that, while lifestyle matters, other factors do too.

A new study now potnetially identifies on of those factors: methionine metabolism.

The researchers studied the blood plasma of healthy centenarians, seniors (average age 76), and ‘young’ adults (average age 28). They then collected blood samples and screened the plasma.

They found that:

Centenarians present a unique plasma methionine-related metabolites profile.

Let’s unpack that briefly. People who make it to 100 in relatively good health have blood work that indicates their bodies process methionine well.

Methionine. (Wikimedia commons, NEUROtiker)

That’s interesting because methionine is an amino acid (a protein building block) that has been implicated in longevity in animal models. Long-lived mammals have lower methionine levels in their blood, and methionine restriction can increase lifespan, for example, up to 40% in rats. Also interesting is that methionine restriction in mice mimics the effects of calorie restriction without having to ‘diet’.

More methionine metabolites in the blood → more ‘processing’ of methionine → less methionine floating around freely →? increased life-/healthspan?

In science lingo, this becomes:

…a specific plasma profile associated with human longevity characterized by an enhanced transsulfuration pathway and tricarboxylic acid (TCA) cycle intermediates, as well as a reduced content of specific amino acids.

Now, methionine is an essential amino acid and it has its uses in the body. So cutting it out entirely — if that’s even possible, it’s everywhere — is not a good idea. It does seem, though, that bodies highly capable of processing the amino acid, due to an integrated and tightly regulated metabolic network, live longer.

Of course, the study looked at a small group of people from Spain, and only at blood plasma levels of methionine — not the concentration in other tissues, both issues gracefully acknowledged by the authors.

Overall: