living longer -- 2/8/23

Today's selection -- from Lifespan: Why We Age -- and Why We Don't Have To by David A. Sinclair, PhD. For decades, scientists have known that restricting calorie intake is a reliable path for longer life:
"As far back as the 1970s … there have been observational stud­ies that strongly suggested long-term calorie restriction could help hu­mans live longer and healthier lives, too.

"In 1978 on the island of Okinawa, famed for its large number of cen­tenarians, bioenergetics researcher Yasuo Kagawa learned that the total number of calories consumed by schoolchildren was less than two-thirds of what children were getting in mainland Japan. Adult Okinawans were also leaner, taking in about 20 percent fewer calories than their main­land counterparts. Kagawa noted that not only were the lifespans of Oki­nawans longer, but their healthspans were, too -- with significantly less cerebral vascular disease, malignancy, and heart disease. 

"In the early 1990s, the Biosphere 2 research experiment provided an­other piece of evidence. For two years, from 1991 to 1993, eight people lived inside a three-acre, closed ecological dome in southern Arizona, where they were expected to be reliant on the food they were growing inside. Green thumbs they weren't, though, and the food they farmed turned out to be insufficient to keep the participants on a typical diet. The lack of food wasn't bad enough to result in malnutrition, but it did mean that the team members were frequently hungry.

"One of the prisoners (and by 'prisoners' I mean 'experimental sub­jects') happened to be Roy Walford, a researcher from California whose studies on extending life in mice are still required reading for scientists en­tering the aging field. I have no reason to suspect that Walford sabotaged the crops, but the coincidence was rather fortuitous for his research; it gave him an opportunity to test his mouse-based findings on human sub­jects. Because they were thoroughly medically monitored before, during, and after their two-year stint inside the dome, the participants gave Wal­ford and other researchers a unique opportunity to observe the numerous biological effects of calorie restriction. Tellingly, the biochemical changes they saw in their bodies closely mirrored those Walford had seen in his long-lived calorie-restricted mice, such as decreased body mass (15 to 20 percent), blood pressure (25 percent), blood sugar level (21 percent), and cholesterol levels (30 percent), among others.

Biosphere 2

"In recent years, formal human studies have begun, but it has turned out to be quite difficult to get volunteer human subjects to reduce their food intake and maintain that level of consumption over long periods. As my colleagues Leonie Heilbronn and Eric Ravussin wrote in The American Journal of Clinical Nutrition in 2003, 'the absence of adequate information on the effects of good-quality, calorie-restricted diets in non­obese humans reflects the difficulties involved in conducting long-term studies in an environment so conducive to overfeeding. Such studies in free-living persons also raise ethical and methodologic issues.'

"In a re­port published in The Journals of Gerontology in 2017, a Duke University research team described how it sought to limit 145 adults to a diet of 25 percent fewer calories than is typically recommended for a healthy lifestyle. People being people, the actual calorie restriction achieved was, on average, about 12 percent over two years. Even that was enough, how­ever, for the scientists to see a significant improvement in health and a slowdown in biological aging based on changes in blood biomarkers.

"These days, there are many people who have embraced a lifestyle that permits significantly reduced caloric intake; about a decade ago, before fasting's most recent revival, some of them visited my lab at Harvard.

"'Isn't it hard to do what you do?' I asked Meredith Averill and her husband, Paul McGlothin, at the time members of CR Society Inter­national and still very much advocates for calorie restriction, who limit themselves to about 75 percent of the calories typically recommended by doctors and sometimes quite a bit less than that. 'Don't you just feel hungry all the time?'

"'Sure, at first,' McGlothin told me. 'But you get used to it. We feel great!'

"At lunch that day, McGlorhin expounded upon the merits of eat­ing organic baby food and slurped down something that looked to me like orange mush. I also noticed rhat both he and Averill were wearing turtlenecks. It wasn't winter. And most folks in my lab are perfectly com­fortable in T-shirts. But with so little fat on their bodies, they needed the extra warmth. Then in his late 60s, McGlothin showed no signs that his diet might slow him down. He was the CEO of a successful marketing company and a former New York State chess champion. He didn't look much younger than his age, though; in large part, I suspect this was because a lack of fat exposes wrinkles, but his blood biochemistry sug­gested otherwise. On his 70th birthday, his health indicators, from blood pressure and LDL cholesterol to resting heart rate and visual acuity, were typical of those of a much younger person. Indeed, they resembled those seen in the long-lived rats on calorie restriction.

"It's true that what we know about the impact of lifelong calorie re­striction in humans comes down to short-term studies and anecdotal experiences. But one of our close relatives has offered us insights into the longitudinal benefits of this lifestyle.

"Since the 1980s, a long-term study of calorie restriction in rhesus monkeys -- our close genetic cousins -- has produced stunningly com­pelling results. Before the study, the maximum known lifespan for any rhesus monkey was 40 years. But of twenty monkeys in the study that lived on calorie-restricted diets, six reached that age, which is roughly equivalent to their reaching 120 in human terms.

"To hit that mark, the monkeys didn't need to live on a calorie-restricted diet for their entire lives. Some of the test subjects were started on a 30 percent reduction regimen when they were middle-aged monkeys.

"CR works to extend the lifespan of mice, even when initiated at 19 months of age, the equivalent of a 60- to 65-year-old human, but the earlier the mice start on CR, the greater the lifespan extension. What longevity benefits of calorie restriction, but it's probably better to start earlier than later, perhaps after age 40, when things really start to go downhill, molecularly speaking.
That doesn't make a CR diet a good plan for everyone. Indeed, even Rozalyn Anderson, a former trainee of mine who's now a famous pro­fessor at the University of Wisconsin and a lead researcher in the rhe­sus study, says a 30 percent calorie-reduced diet for humans, long term, amounted in her mind to a 'bonkers diet.'

"It's certainly not bonkers for everyone, though, especially consider­ing that calorie restriction hasn't been demonstrated only to lengthen life but also to forestall cardiac disease, diabetes, stroke, and cancer. It's not just a longevity plan; it's a vitality plan.

"It's nonetheless a hard sell for many people. It takes strong willpower to avoid the fridge at home or snacks at work. There's an adage in my field: if calorie restriction doesn't make you live longer, it will certainly make you feel that way.

"But it turns out that's okay, because research is increasingly demonstrating that many of the benefits of a life of strict and uncompromising calorie restriction can be obtained in another way. In fact, that way might be even better.

"To ensure a genetic response to a lack of food, hunger doesn't need to be the status quo. Once we've grown accustomed to stress, after all, it's no longer as stressful. Intermittent fasting, or IF-eating normal portions of food but with periodic episodes without meals -- is often portrayed as a new innovation in health. But long before my friend Valter Longo at the University of California, Los Angeles, began touting the benefits of IF, scientists had been studying the effects of periodic calorie restriction for the better part of a century."



David A. Sinclair, PhD with Matthew D. LaPlante


Lifespan: Why We Age -- and Why We Don't Have To


Atria Books


Copyright 2019 by David A. Sinclair, PhD


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