summarize this "Of course, there are almost certainly confounders here, just as with all
observational study, including that of nutrition. But at least five factors
[*3]
increase my confidence in at least the partial causality of this relationship.
First, the magnitude of the effect size is very large. Second, the data are
consistent and reproducible across many studies of disparate populations.
Third, there is a dose-dependent response (the fitter you are, the longer you
live). Fourth, there is great biologic plausibility to this effect, via the known
mechanisms of action of exercise on lifespan and healthspan. And fifth,
virtually all experimental data on exercise in humans suggest that it supports
improved health.
As the authors of the JAMA study concluded, “Cardiorespiratory fitness is
inversely associated with long-term mortality with no observed upper limit of
benefit [emphasis mine]. Extremely high aerobic fitness was associated with
the greatest survival.”
I can’t tell you, from these data, that simply having a high VO2 max will
offset your high blood pressure or your smoking habit, as much as these
hazard ratios suggest it might. Without a randomized controlled trial, we can’t
know for sure, but I kind of doubt it. But I can say with a very high degree of
certainty that having a higher VO2 max is better for your overall health and
longevity than having a lower VO2
 max. Period.
Even better news, for our purposes, is that VO2 max can be increased via
training. We can move the needle a lot on this measure of fitness, as we’ll see.
—
The strong association between cardiorespiratory fitness and longevity has
long been known. It might surprise you, as it did me, to learn that muscle may
be almost as powerfully correlated with living longer. A ten-year
observational study of roughly 4,500 subjects ages fifty and older found that
those with low muscle mass were at 40 to 50 percent greater risk of mortality
than controls, over the study period. Further analysis revealed that it’s not the
mere muscle mass that matters but the strength of those muscles, their ability
to generate force. It’s not enough to build up big pecs or biceps in the gym—
those muscles also have to be strong. They have to be capable of creating
force. Subjects with low muscle strength were at double the risk of death,
while those with low muscle mass and/or low muscle strength, plus metabolic
syndrome, had a 3 to 3.33 times greater risk of all-cause mortality.
Strength may even trump cardiorespiratory fitness, at least one study
suggests. Researchers following a group of approximately 1,500 men over
forty with hypertension, for an average of about eighteen years, found that
even if a man was in the bottom half of cardiorespiratory fitness, his risk of
all-cause mortality was still almost 48 percent lower if he was in the top third
of the group in terms of strength versus the bottom third.
[*4]
It’s pretty much the same story we saw with VO2 max: The fitter you are,
the lower your risk of death. Again, there is no other intervention, drug or
otherwise, that can rival this magnitude of benefit. Exercise is so effective
against diseases of aging—the Horsemen—that it has often been compared to
medicine.
John Ioannidis, a Stanford scientist with a penchant for asking provocative
questions, decided to test this metaphor literally, running a side-by-side
comparison of exercise studies versus drug studies. He found that in
numerous randomized clinical trials, exercise-based interventions performed
as well as or better than multiple classes of pharmaceutical drugs at reducing
mortality from coronary heart disease,
[*5] prediabetes or diabetes, and stroke.
Even better: You don’t need a doctor to prescribe exercise for you.
Much of this effect, I think, likely has to do with improved mechanics:
exercise strengthens the heart and helps maintain the circulatory system. As
we’ll see later in this chapter, it also improves the health of the mitochondria,
the crucial little organelles that produce energy in our cells (among other
things). That, in turn, improves our ability to metabolize both glucose and fat.
Having more muscle mass and stronger muscles helps support and protect the
body—and also maintains metabolic health, because those muscles consume
energy efficiently. The list goes on and on, but simply put, exercise helps the
human “machine” perform far better for longer.
At a deeper biochemical level, exercise really does act like a drug. To be
more precise, it prompts the body to produce its own, endogenous drug-like
chemicals. When we are exercising, our muscles generate molecules known as
cytokines that send signals to other parts of our bodies, helping to strengthen
our immune system and stimulate the growth of new muscle and stronger
bones. Endurance exercise such as running or cycling helps generate another
potent molecule called brain-derived neurotrophic factor, or BDNF, that
improves the health and function of the hippocampus, a part of the brain that
plays an essential role in memory. Exercise helps keep the brain vasculature
healthy, and it may also help preserve brain volume. This is why I view
exercise as a particularly important part of the tool kit for patients at risk of
developing Alzheimer’s disease—such as Stephanie, the woman with the
high-risk Alzheimer’s genes whom we met in chapter 9.
The data demonstrating the effectiveness of exercise on lifespan are as
close to irrefutable as one can find in all human biology. Yet if anything, I
think exercise is even more effective at preserving healthspan than extending
lifespan. There is less hard evidence here, but I believe that this is where
exercise really works its magic when applied correctly. I tell my patients that
even if exercise shortened your life by a year (which it clearly does not), it
would still be worthwhile purely for the healthspan benefits, especially in
middle age and beyond.
One of the prime hallmarks of aging is that our physical capacity erodes.
Our cardiorespiratory fitness declines for various reasons that begin with
lower cardiac output, primarily due to reduced maximum heart rate. We lose
strength and muscle mass with each passing decade, our bones grow fragile
and our joints stiffen, and our balance falters, a fact that many men and
women discover the hard way, by falling off a ladder or while stepping off a
curb.
To paraphrase Hemingway, this process happens in two ways: gradually,
and then suddenly. The reality of the situation is that old age can be really
tough on our bodies. Longitudinal and cross-sectional studies find that fat-free
mass (meaning mostly muscle mass) and activity levels remain relatively
consistent as people age from their twenties and thirties into middle age. But
both physical activity levels and muscle mass decline steeply after about age
sixty-five, and then even more steeply after about seventy-five. It’s as if
people just fall off a cliff sometime in their mid-seventies.
By age eighty, the average person will have lost eight kilograms of
muscle, or about eighteen pounds, from their peak. But people who maintain
higher activity levels lose much less muscle, more like three to four kilograms
on average. While it’s not clear which direction the causation flows here, I
suspect it’s probably both ways: people are less active because they are
weaker, and they are weaker because they are less active.
Continued muscle loss and inactivity literally puts our lives at risk. Seniors
with the least muscle mass (also known as lean mass) are at the greatest risk
of dying from all causes. One Chilean study looked at about one thousand
men and four hundred women, with an average age of seventy-four at
enrollment. The researchers divided the subjects into quartiles, based on their
appendicular lean mass index (technically, the muscle mass of their
extremities, arms and legs, normalized to height), and followed them over
time. After twelve years, approximately 50 percent of those in the lowest
quartile were dead, compared to only 20 percent of those in the highest
quartile for lean mass. While we can’t establish causality here, the strength
and reproducibility of findings like this suggest this is more than just a
correlation. Muscle helps us survive old age.
This is another area where lifespan and healthspan overlap to a great
extent. That is, I suspect that having more muscle mass delays death precisely
because it also preserves healthspan. This is why I place so much emphasis on
maintaining our musculoskeletal structure—which I call the “exoskeleton,” à
la Terminator, for lack of a better term.
Your exoskeleton (muscle) is what keeps your actual skeleton (bones)
upright and intact. Having more muscle mass on your exoskeleton appears to
protect you from all kinds of trouble, even adverse outcomes following
surgery—but most important, it is highly correlated with a lower risk of
falling, a leading but oft-ignored cause of death and disability in the elderly.
As figure 10 reveals, falls are by far the leading cause of accidental deaths in
those ages sixty-five and older—and this is without even counting the people
who die three or six or twelve months after their nonfatal but still serious fall
pushed them into a long and painful decline. Eight hundred thousand older
people are hospitalized for falls each year, according to the CDC."