Saturday, March 02, 2013

How to Live 30% Longer (Maybe More)

If there's one thing we know about longevity, it's that the surest, safest way to get an organism to live longer is to subject it to a reduced-calorie diet. Simply deprive an organism of food, not to the point of starvation (of course) but to the point where the organism has the minimal nutrition that will ensure healthy survival, and the organism will live longer. Often dramatically so.

In 1935, Clive McCay, Mary Crowell, and L.A. Maynard published the first scientific report on this subject, noting that laboratory rats fed a severely calorie-restricted diet lived up to twice as long as rats that ate ad libitum.

Calorie-restriction (CR) experiments have since been done with a wide variety of organisms. The results have been dramatic, and highly reproducible across a broad range of species. A decrease in caloric input of 30% to 40% invariably brings significant increases in the mean and maximum life spans of yeast (Saccharomyces cerevisiae), rotifers, nematodes (Caenorhabditis elegans), fruit flies (Drosophila melanogaster), medflies (Ceratitis capitata), spiders, fish (guppies, zebrafish), rodents (hamsters, rats, mice), dogs, and others. As a side-benefit, morbidity due to cancer, cardiovascular disease, diabetes, kidney disease, and autoimmune disease generally declines significantly in calorie-restricted populations versus organisms allowed to eat ad libitum.

The longevity-promoting effect of calorie restriction is so stark and obvious, across so many species lines, you wouldn't think anyone would doubt its applicability to humans. For ethical reasons, a formal experiment hasn't been run on humans, but two major studies are underway to see if the CR-longevity effect holds true for primates. One experiment is being conducted by the University of Wisconsin-Madison; the other is by the National Institute on Aging (NIA) of the National Institutes of Health (NIH). These studies began in 1989 and 1987, respectively. Both projects involve rhesus monkeys (Macaca mulatta). In a lab environment, the median life expectancy of rhesus monkeys is approximately 26 years. About 10% survive beyond 35 years; maximum lifespan is roughly 40 years.

In a 1986 study, UCLA researchers divided 349 mice into six groups. The control group (NP) was allowed to eat Purina Laboratory Chow (23% protein) ad libitum. All other groups ate carefully formulated diets, but in different amounts. One group got 85 kcal of food per week. Another got 50 kcal/wk, another got 50 kcal with reduced protein, another got 50 kcal/wk starting from before weaning, and one group got 40 kcal/wk. The respective survival curves for these groups are shown above. Each dot on each curve represents a death. Notice that no ad-libitum animal lived beyond 36 months. Almost a third of the 40 kcal/wk animals lived beyond 50 months. (Click to enlarge.)

The rhesus-monkey CR studies have shown mixed results so far. The Wisconsin group found that their calorie-reduced monkeys definitely lived longer; the NIA group found no convincing evidence of life extension (even though they noted "four CR monkeys and one control from the old-onset group have lived beyond 40 years.") Neither study is finished (in the sense of all animals having died) and some have questioned the NIA protocol, inasmuch as the NIA monkeys got a diet of 56.9% carbohydrate, 17.3% protein, and 5% fat, which is essentially a high-carb diet equivalent to eating ramen noodles. A thorough and impartial third-party overview of existing primate work (including not only the NIA and Wisconsin studies but a handful of others) can be found in "Calorie Restriction and Aging in Nonhuman Primates" by Joseph W. Kemnitz, ILAR J. 2011 February 8; 52(1): 66–77.

But do we really have to run experiments like this on monkeys to see if the CR-longevity effect applies to humans? Anecdotally, we all know there are no 90-year-old Sumo wrestlers. We also know it's unlikely scientists will discover an uncharted village, high above the tree line in the Andes, where 100-year-old village elders angrily throw still-smoldering cigar butts at their pregnant 80-year-old wives for not smearing enough extra icing on their Cinnabons.

In the Blue Zones that have been studied so far, there's one constant: Low body mass index.

The Japanese district of Okinawa has the longest average lifespan in the world and the highest documented percentage of centenarians (people living beyond 100). Consistent with CR experiments in animals, Okinawans eat around 40% fewer calories than Americans and 17% fewer calories than the Japanese average. The caloric intake of Okinawan children is 36% below the Japanese recommended intake. The typical adult BMI (body mass index) is 18 to 22. (For a five-foot-nine-inch man, that's a weight of 122 to 149 pounds.) No one rides a Scootie to McDonalds.

Blue Zoners not only don't eat much, they treat meat as poison, although in Sardinia, the natives sometimes eat Pecorino, a special cheese made from special milk from special sheep that graze on special grass. This cheese is said to have super-high concentrations of CLA (conjugated linoleic acid), a particular omega-3 fatty acid.
This photograph was not taken in Okinawa.

Most Blue Zoners are religious (or at least highly spiritual), but in the Costa Rican Blue Zone, adultery runs as high as 70%. Obviously these people are outliers. Adultery correlates with early mortality in most cultures.

It also helps to have good genes, of course. And most Blue Zones are genetically isolated (hence probably share a lot of "good genes"). But longevity is currently thought to be no more than 25% genetic. When it comes to living a long life, it's mostly what you do with your body that matters, not what you're born with.

Bottom line, we already know that overweight (not just obesity, but overweight) is positively correlated with type 2 diabetes, hypertension, stroke, coronary artery disease, pulmonary embolism, asthma, chronic back ailments, osteoarthritis (and related hip and knee replacement), gallbladder disease, obstructive sleep apnia, colorectal cancer, kidney cancer, pancreatic cancer, endometrial cancer, ovarian cancer, and post-menopausal breast cancer. Every day, we see the results of the struggle between CR and longevity, in real people, right in front of us, in real time. We see human beings eating ad libitum, at McDonalds and elsewhere, every day. Those are the control group. (Remember, in the animal studies, the control-group individuals are those who are allowed to eat ad libitum.) The CR studies all say the same thing: you can live a long time, or you can eat ad libitum. Not both.

The starting point for longer life expectancy isn't to put more money into cancer research. It's to put less food in your mouth. It's that simple -- and that hard.