The Two Types of Aging

An aging body is changing in more ways than just those obvious to visual inspection.

It is the biochemical wear and tear that inevitably progresses as time passes. Let’s call this inevitable part of aging primary aging.

It is the part of aging we can do comparatively little to prevent [1]. But you can, and many of us, do a very good job at accelerating this part of aging.

Let’s call it secondary aging.

It is driven primarily by lifestyle choices. Let yourself become overweight, or sedentary, or take up smoking, and chronic inflammation will eventually set in.

Of course, inflammation is not a bad thing per se. It is necessary to cope with damaging agents, such as infections, and it is crucial for survival. But let your lifestyle choices become a constant source of damaging agents, and what you create is a chronic low-grade inflammatory status.

Inflammaging

It contributes to all those diseases that we associate with aging: heart disease, stroke, diabetes, kidney failure, dementia, frailty.

Inflammation is so central to aging that the term inflammaging has become a recognized concept to describe secondary aging.

But if not-so-prudent lifestyle choices are its cause, alternative lifestyle choices should be its remedy.

Exercise Is Medicine

The most powerful of those remedies is exercise. There is no drug that outperforms it [2]. It comes in many shades, from aerobic to resistance, from continuous moderate intensity to high intensity interval exercise, and from dynamic to isometric strength training. Each variety has its own fan community, each claiming superiority for the purpose of healthy aging.

But which one is really superior? Particularly for You?

That was the question a team of researchers attempted to answer choosing the format of a meta-analysis [3]. The casual reader is supposed to be impressed when they hear the word “meta-analysis”.

Because, in theory, these meta-analyses extract the true answers to a research question, by taking into consideration all the relevant studies that have been performed on that subject.

So, let us look a little closer at this meta-analysis about the effects of different exercise modes on PWV, and by extension, on vascular aging.

The researchers gathered their evidence from several studies that covered almost the entire spread of exercise modes: aerobic, dynamic resistance and isometric resistance exercise.

In case you are not familiar with the difference between the latter two: “dynamic” means doing a set of push-ups, for example, whereas in the isometric version you hold a fixed push-up position for a length of time.

To be included in their analysis, studies needed to meet strict requirements. First, only randomized controlled trials (RCT) were permitted. The RCT is the gold standard of trial designs to discover cause-effect relationships.

Second, all studies used pulse wave velocity (PWV) as the criterion effect. PWV is the gold standard biomarker for arterial stiffness. The degree of arterial stiffness is a key indicator of early vascular aging (EVA). And therefore, EVA is something you would like to avoid – remember the old adage: you are as old as your arteries.

Third, the researchers considered only studies performed on hypertensive patients. This is important because hypertension is one of the most common consequences of EVA.

So, when you want to know which exercise is best to treat or reverse EVA, you also know what is best to prevent it in the first place.

Here is their conclusion:

“…exercise interventions using aerobic, combined and isometric resistance exercise programmes, are effective to reduce PWV in patients with hypertension.”…

…but dynamic resistance exercise alone didn’t make the grade.

And off you go doing your aerobic or isometric resistance exercises, while neglecting dynamic resistance exercise, to prevent or reverse secondary aging. Good idea?

No.

Here is why:

The Problem With (This) Meta-Analysis

First, it is surprising to see that only 14 studies met the researchers’ selection criteria.

Over the past 30 years 900 studies had examined the exercise-PWV association. Of those 900 studies only 211 were RCTs, and of those only 14 made the grade for the meta-analysis.

Given that only 350 patients had been included in those 14 studies, we really know very little about the effects of exercise on EVA, don’t we?

Second, even the little that we know is compromised.

Take the 2 studies on isometric resistance training as an example. Both studies used handgrip exercise only. The “largest” study had 24 patients in the intervention group doing 4 sets of 2-minute handgrip exercise (at 30% of their maximum voluntary contraction) 3 times a week [4]. That’s not exercise. Not in my eyes.

Of those 24 patients almost half had dropped out during the 12-week study duration. That study reported a drop of 12 mmHg for those “exercisers”.

If it was so easy to reduce blood pressure, don’t you think you would find isometric exercise on the very top of medical guidelines? Only you don’t find it there.

On to the dynamic resistance exercise studies. The larger of the two had only 15 patients in the intervention group. Is that enough to conclude that dynamic exercise doesn’t work on your PWV?

No.

But that’s not the point I want to make.

My point is, that you shouldn’t take anything that is dressed up as a systematic review or meta-analysis at face value.

Am I the only one saying so?

Again, no.

John Ioannidis, thinks so, too. He is a Stanford professor of medicine, of health research and policy, and of statistics, and he is the director of the Stanford Meta-Research Innovation Center, whose purpose is to advance excellence in scientific research.

He says:

“Possibly, the large majority of produced systematic reviews and meta-analyses are unnecessary, misleading, and/or conflicted.” [5]

That’s jaw-dropping. And it should make you sceptical whenever your favourite media touts some health claim with the reference to a meta-analysis or systematic review.

But it doesn’t help you find the exercise that slows down your rate of secondary aging.

Let’s look at how exercise affects blood pressure. Being a consequence, and sometimes a cause, of arterial aging, and also being the main risk factor for heart disease, stroke, heart failure and the like, the effects of exercise on blood pressure should not be much different from exercise effects on vascular aging.

The advantage of looking at blood pressure is that the effects of exercise on blood pressure are much better studied.

A 2018 network meta-analysis of the comparative effects of exercise and BP lowering medications came to the following conclusion [6]:

“…all types of exercise … were effective in lowering baseline SBP.”

And

“…the SBP-lowering effect of exercise among hypertensive populations appears similar to that of commonly used antihypertensive medications”

Why do I quote a meta-analysis, when I just kind of discredited it?

Because this is a network meta-analysis. It goes a step beyond meta-analysis. While the latter simply pools data of several studies, the former uses a networking technique to investigate the relative effectiveness of different interventions. If you are so inclined feel free to read up on that subject here [7].

Back to the results.

The common denominator is the large effect size differences between studies and, more importantly, between individuals. That means, there is no one-size-fits-all rule when it comes to exercise.

And there is one more discovery to that: Non-responders to exercise do not exist. It is simply a matter of dose.

“Refuting the myth of non-response to exercise training: ‘non-responders’ do respond to higher dose of training” [8]

Taken together, both insights suggest that reading studies will not uncover the right type and dose of exercise for you. The type and dose you need to achieve to slowing down secondary aging are unique to you.

Here is what you can do.

N-of-1

Make yourself a clinical trial. One in which you act as your own intervention and control “group”. And find out by trial-and-error, which exercise type and dose has the desired effect on your PWV or your blood pressure.

Medical science has a name for such trial: N-of-1.

The “N” in clinical terminology stands for the number of participants in a study.

And it works like this: You’ll first go through a baseline phase (ideally 14 days), during which you keep living as you do right now. Then you try the exercise mode of your choice (or any other health behavior) for a period. N-of-1 algorithms will then extract the effect and effect size from the biomarker data (PWV or blood pressure) that you have collected throughout both phases.

Here is a short video that explains the principle.

N-of-1 is a term that you should remember, because soon it will turn from being completely unknown to becoming THE way of doing personalised medicine.

It will be a bit like it was with ChatGPT. Completely unknown until late 2022, and half a year later the hot topic at every dinner table.

My team and I have operationalised N-of-1 methods so that every layperson can use it to find not only the right exercise, but all the right health habits to achieve their health goals. Of which the most important is, of course, slowing down, stopping, or even reversing secondary aging.

You can visit our website to learn more about how this works.

And best of all, if you have a health concern that lies within our capacity to address it, and if you have what it takes to address it through lifestyle change (which is often not easy, particularly when moving from being sedentary to becoming active), then you can send me an e-mail, and I will consider you for a free-of-charge enrolment into our beta-test program.

That offer stands until the first 20 places are filled.

Remember: It is never too early to start putting the brakes on secondary aging.