A recurring theme in research on aging is that of growth vs longevity. In essence, they’re opposed: more growth means shorter life, and less growth means longer life. The activation of physiological mechanisms in growth promotes aging, and deactivating them promotes longevity. Big animals die younger.
Evidence in non-human animals
Between species, larger animals tend to live longer. Elephants live longer than mice, who live longer than flies and worms. Mikhail Blagosklonny, the noted scientist who studies aging, sums it up as “Big mice die young but large animals live longer“.
As the article says, within species, larger animals die younger. Small mice live longer than big mice, because they grow less.
Why do larger animals, between species, live longer? Larger animals have fewer predators and low rates of accidental death; therefore, natural selection has worked on them to evolve longer lives, with more robust anti-aging mechanisms. In contrast, if the average mouse is dead at two years of age from predation or other accidents of life, then there’s nothing for natural selection to work on.
Calorie restriction is the most robust life-extension intervention known to science. Animals live longer when their food is restricted. The causes of this are hotly debated, but one theory is that since food promotes growth, restricting food hinders growth and extends life. Even when animals are fully grown, food activates the growth mechanism and effectively shortens life.
Evidence in humans
There’s a lot of evidence that larger humans die younger.
Obesity by definition means higher than normal body fat and thus higher body weight. The adverse health effects of obesity are well known.
Even when body fat remains the same, however, larger size appears to mean shorter life.
Among professional baseball players, larger size was strongly correlated to a lower age at death. See graph below.
Note that BMI for all the baseball players is quite similar, so age at death was not related to being overweight, but to total body weight and height. Taller players died younger.
Among different ethnic groups in California, death rates correspond to their average body mass index, in order from lowest to highest: Asian Indian, Chinese, Japanese, Hispanic, White, African-American. (Hispanics actually weight the most of these groups, evidence for the Hispanic health paradox.)
Among Olympic athletes, those who set records at younger ages died younger. “Early and extraordinary peaks in physical performance come with a longevity cost“.
Life history theory postulates a trade-off between development and maintenance. This trade-off is observed when comparing life histories of different animal species. In humans, however, it is debated if variation in longevity is explained by differences in developmental traits. Observational studies found a trade-off between early and high fecundity and longevity in women. Development encompasses more than fecundity and also concerns growth and physical performance. Here, we show a life history trade-off between early and above average physical performance and longevity in male Olympic athletes. Athletes who peaked at an earlier age showed 17-percent increased mortality rates and athletes who ranked higher showed 11-percent increased mortality rates. Male athletes who had both an early and extraordinary peak performance suffered a 4.7-year longevity cost. This is the first time a life history trade-off between physical performance and longevity has been found in humans. This finding deepens our understanding of early developmental influences on the variation of longevity in humans.
The authors say, “It is important to note that cocaine was available since the first Olympic games and could have played a role in the association.” I’ve never heard before of Olympic athletes using cocaine, but that would certainly shorten lives. I suppose it’s completely unknown how many athletes used it.
Basketball players, who are of course much taller than average, don’t seem to live very long. Anecdotally,
Within the past year, the NBA has seen a spate of deaths among some of its notable retired big men — among them Moses Malone, Darryl Dawkins and Anthony Mason, none older than 60.
And now Larry Bird admits, he doesn’t expect to live to a ripe old age.
Another piece of evidence: women live longer than men, and women are smaller.
Kitavans, Okinawans, and Cretans
The people of Kitava, Okinawa, and Crete are famous for better health and longer lives. Their diets and lifestyles have been extensively studied and have given rise to concepts like the Mediterranean and Okinawan diets, the Blue Zones, and the importance of religion and social ties for health and longevity.
What seems to have escaped many researchers is that these people are all small.
Kitavans show no evidence of heart disease or strokes and cancer appears to be rare. Young Kitavan men average 125 lbs (57 kg), and Kitavan men over the age of 60 average 107 lbs (49 kg). Kitavan women are also small. By the way, 80% of Kitavans smoke, yet appear to be in excellent health.
Okinawa has a high number of centenarians. The average male Okinawan centenarian weighs 97 lbs (44 kg); the average female centenarian weighs 81 lbs (36.7 kg). (ibid.)
The average man in Crete has a BMI of 22.8, the lowest of any surrounding Mediterranean communities, and they have the lowest death rate. “Cretans have 1/2 the all-cause and <1/20 coronary heart disease (CHD) mortality of larger northern Europeans.” (ibid.)
If size has such a large correlation to death rate, it makes me wonder how important the diets or other lifestyle factors of these people are. Maybe we’ve been looking at the wrong things, and all along it’s been their size that’s the most important. Of course, their diets affect how large they grow too.
Centenarians are on average short. In a group of Italian centenarians, average height was 156 cm, or 5’1.4″. “Mean values for height and weight of nonagenarians and centenarians were at the lower percentile values of the distributions reported for elderly American and European subjects…” Height was calculated using a formula based on knee height, so that spinal shrinkage did not influence results.
Okinawan centenarians are of “short stature”. In another group of centenarians, women were on average 2.5 cm (1 inch) shorter than controls, but men were not shorter.
It also appears to be trivially easy to find examples of long-lived short people. For example, just the other day the NY Times ran an article about Robert Marchand, the now-celebrated 105-year-old Frenchman who keeps breaking cycling records. It turns out that M. Marchand is 5’0″ tall, and weighs 115 lbs. Salustiano Sanchez, who once held the rank of world’s oldest man, and who died at age 112, was nicknamed “Shorty”.
So, there seems to be good evidence, both human and animal, that larger and/or taller humans and animals have shorter lives. Noted aging researcher Luigi Fontana has calculated that “risks of developing type 2 diabetes, cardiovascular disease, and several types of cancer” are lowest at a BMI of 21 to 22, and rise from there.
Why is there an inverse relation between growth and longevity?
One answer centers on mTOR, the cellular growth controller. When mTOR is activated after maturity, physiological reactions occur that promote aging. This is the “quasi-programmed” theory of aging. mTOR is necessary for growth and development, but continues in a mindless loop afterwards, accelerating aging.
Interventions that inhibit constitutive activation of mTOR are either good for health or extend lifespan:
Interventions and conditions that promote mTOR constitutive activation are detrimental to longevity:
- growth hormone supplementation. Acromegaly, or excess growth hormone, results in a 2 to 3-fold higher death rate.
- anabolic steroids
- insulin resistance.
However, an attribute like height is under strong genetic control, so it’s safe to say that genes have a lot to do with the growth vs longevity effect.
On the other hand, heights have increased over the past two centuries. Italian conscripts increased in height by about 5 inches from 1854 to 1963, and current rates of height increase are from 10 to 30 mm a decade. That increase must be environmental, and could be due to better nutrition and fewer childhood diseases.
What to do about it
You can’t control your height, so what can you do about this association?
- Stay lean with a good, muscular body composition and low body fat.
- Use some of the interventions listed above, such as resveratrol, intermittent fasting, and dumping iron.
That’s about it. Having good body composition will ensure that you don’t have insulin resistance. Essentially, all of these things go together: insulin sensitivity, normal rhythms of autophagy, and good body composition. mTOR inhibits autophagy, the cellular self-cleansing process which is so critical to aging.
Beyond that, anti-aging treatments that inhibit mTOR are underway. You can already get metformin if you find the right doctor, although OTC berberine might be as good. Rapamycin is a promising anti-aging drug that’s being extensively studied, although it has its downsides. It seems possible that pulse dosing of rapamycin, perhaps once weekly, could have anti-aging effects without many of the downsides. Mikhail Blagosklonny believes that “rapamycin will become the cornerstone of anti-aging therapy in our life time”.