Octogenarians, Nonagenarians, & Centenarians

Highlights
? Circulating DHEAS levels are highly elevated in young adults and subsequently show a marked age-related decline.
? In rhesus monkeys, plasma DHEAS has a well-defined diurnal rhythm, with peaks in the morning.
? Despite early promise, recent findings suggest that circulating DHEAS levels may not be good biomarkers of aging in calorie restriction studies.


Urbanski HF, Mattison JA, Roth GS, Ingram DK. Dehydroepiandrosterone sulfate (DHEAS) as an endocrine marker of aging in calorie restriction studies. Exp Gerontol. ScienceDirect.com - Experimental Gerontology - Dehydroepiandrosterone sulfate (DHEAS) as an endocrine marker of aging in calorie restriction studies

The adrenal steroid, dehydroepiandrosterone sulfate (DHEAS), is generally regarded as being a reliable endocrine marker of aging, because in humans and nonhuman primates its circulating concentrations are very high during young adulthood, and the concentrations then decline markedly during aging. Despite promising results from early studies, we were recently surprised to find that caloric restriction (CR) did little to prevent or delay the decline of DHEAS concentrations in old rhesus macaques. Here we summarize the use of circulating DHEAS concentrations as a biomarker of aging in CR studies and suggest reasons for its limited value. Although DHEAS can reliably predict aging in animals maintained on a standard diet, dietary manipulations may affect liver enzymes involved in the metabolism of steroid hormones. Consequently, in CR studies the reliability of using DHEAS as a biomarker of aging may be compromised.
 
Highlights
º SIRT3 is highly enriched in HSCs and suppressed in differentiated hematopoietic cells
º SIRT3 regulates HSC self-renewal under stress or at an old age
º SIRT3 regulates mitochondrial metabolic homeostasis and reduces ROS in HSCs
º SIRT3 is suppressed with age, and its upregulation rejuvenates aged HSCs


Brown K, Xie S, Qiu X, et al. SIRT3 Reverses Aging-Associated Degeneration. Cell Reports. Cell Reports - SIRT3 Reverses Aging-Associated Degeneration

Despite recent controversy about their function in some organisms, sirtuins are thought to play evolutionarily conserved roles in lifespan extension. Whether sirtuins can reverse aging-associated degeneration is unknown. Tissue-specific stem cells persist throughout the entire lifespan to repair and maintain tissues, but their self-renewal and differentiation potential become dysregulated with aging.

We show that SIRT3, a mammalian sirtuin that regulates the global acetylation landscape of mitochondrial proteins and reduces oxidative stress, is highly enriched in hematopoietic stem cells (HSCs) where it regulates a stress response. SIRT3 is dispensable for HSC maintenance and tissue homeostasis at a young age under homeostatic conditions but is essential under stress or at an old age. Importantly, SIRT3 is suppressed with aging, and SIRT3 upregulation in aged HSCs improves their regenerative capacity.

Our study illuminates the plasticity of mitochondrial homeostasis controlling stem cell and tissue maintenance during the aging process and shows that aging-associated degeneration can be reversed by a sirtuin.
 
The Island Where People Forget to Die
The Island Where People Forget to Die - NYTimes.com

October 24, 2012
By DAN BUETTNER

In 1943, a Greek war veteran named Stamatis Moraitis came to the United States for treatment of a combat-mangled arm. He’d survived a gunshot wound, escaped to Turkey and eventually talked his way onto the Queen Elizabeth, then serving as a troopship, to cross the Atlantic. Moraitis settled in Port Jefferson, N.Y., an enclave of countrymen from his native island, Ikaria. He quickly landed a job doing manual labor. Later, he moved to Boynton Beach, Fla. Along the way, Moraitis married a Greek-American woman, had three children and bought a three-bedroom house and a 1951 Chevrolet.

One day in 1976, Moraitis felt short of breath. Climbing stairs was a chore; he had to quit working midday. After X-rays, his doctor concluded that Moraitis had lung cancer. As he recalls, nine other doctors confirmed the diagnosis. They gave him nine months to live. He was in his mid-60s.

Moraitis considered staying in America and seeking aggressive cancer treatment at a local hospital. That way, he could also be close to his adult children. But he decided instead to return to Ikaria, where he could be buried with his ancestors in a cemetery shaded by oak trees that overlooked the Aegean Sea. He figured a funeral in the United States would cost thousands, a traditional Ikarian one only $200, leaving more of his retirement savings for his wife, Elpiniki. Moraitis and Elpiniki moved in with his elderly parents, into a tiny, whitewashed house on two acres of stepped vineyards near Evdilos, on the north side of Ikaria. At first, he spent his days in bed, as his mother and wife tended to him. He reconnected with his faith. On Sunday mornings, he hobbled up the hill to a tiny Greek Orthodox chapel where his grandfather once served as a priest. When his childhood friends discovered that he had moved back, they started showing up every afternoon. They’d talk for hours, an activity that invariably involved a bottle or two of locally produced wine. I might as well die happy, he thought.

In the ensuing months, something strange happened. He says he started to feel stronger. One day, feeling ambitious, he planted some vegetables in the garden. He didn’t expect to live to harvest them, but he enjoyed being in the sunshine, breathing the ocean air. Elpiniki could enjoy the fresh vegetables after he was gone.

Six months came and went. Moraitis didn’t die. Instead, he reaped his garden and, feeling emboldened, cleaned up the family vineyard as well. Easing himself into the island routine, he woke up when he felt like it, worked in the vineyards until midafternoon, made himself lunch and then took a long nap. In the evenings, he often walked to the local tavern, where he played dominoes past midnight. The years passed. His health continued to improve. He added a couple of rooms to his parents’ home so his children could visit. He built up the vineyard until it produced 400 gallons of wine a year. Today, three and a half decades later, he’s 97 years old — according to an official document he disputes; he says he’s 102 — and cancer-free. He never went through chemotherapy, took drugs or sought therapy of any sort. All he did was move home to Ikaria.

I met Moraitis on Ikaria this past July during one of my visits to explore the extraordinary longevity of the island’s residents. For a decade, with support from the National Geographic Society, I’ve been organizing a study of the places where people live longest. The project grew out of studies by my partners, Dr. Gianni Pes of the University of Sassari in Italy and Dr. Michel Poulain, a Belgian demographer. In 2000, they identified a region of Sardinia’s Nuoro province as the place with the highest concentration of male centenarians in the world. As they zeroed in on a cluster of villages high in Nuoro’s mountains, they drew a boundary in blue ink on a map and began referring to the area inside as the “blue zone.” Starting in 2002, we identified three other populations around the world where people live measurably longer lives than everyone else. The world’s longest-lived women are found on the island of Okinawa. On Costa Rica’s Nicoya Peninsula, we discovered a population of 100,000 mestizos with a lower-than-normal rate of middle-age mortality. And in Loma Linda, Calif., we identified a population of Seventh-day Adventists in which most of the adherents’ life expectancy exceeded the American average by about a decade.

In 2003, I started a consulting firm to see if it was possible to take what we were learning in the field and apply it to American communities. We also continued to do research and look for other pockets of longevity, and in 2008, following a lead from a Greek researcher, we began investigating Ikaria. Poulain’s plan there was to track down survivors born between 1900 and 1920 and determine when and where individuals died. The approach was complicated by the fact that people often moved around. That meant that not only were birth and death records required, but also information on immigration and emigration.

The data collection had to be rigorous. Earlier claims about long-lived people in places like Ecuador’s Vilcabamba Valley, Pakistan’s Hunza Valley or the Caucasus Mountains of Georgia had all been debunked after researchers discovered that many residents didn’t actually know their ages. For villagers born without birth certificates, it was easy to lose track. One year they were 80; a few months later they were 82. Pretty soon they claimed to be 100. And when a town discovers that a reputation for centenarians draws tourists, who’s going to question it? Even in Ikaria, the truth has been sometimes difficult to nail down. Stories like the one about Moraitis’s miraculous recovery become instant folklore, told and retold and changed and misattributed. (Stories about Moraitis have appeared on Greek TV.) In fact, when I was doing research there in 2009, I met a different man who told me virtually the exact same story about himself.

The study would try to cut through the stories and establish the facts about Ikaria’s longevity. Before including subjects, Poulain cross-referenced birth records against baptism or military documentation. After gathering all the data, he and his colleagues at the University of Athens concluded that people on Ikaria were, in fact, reaching the age of 90 at two and a half times the rate Americans do. (Ikarian men in particular are nearly four times as likely as their American counterparts to reach 90, often in better health.) But more than that, they were also living about 8 to 10 years longer before succumbing to cancers and cardiovascular disease, and they suffered less depression and about a quarter the rate of dementia. Almost half of Americans 85 and older show signs of Alzheimer’s. (The Alzheimer’s Association estimates that dementia cost Americans some $200 billion in 2012.) On Ikaria, however, people have been managing to stay sharp to the end.

Ikaria, an island of 99 square miles and home to almost 10,000 Greek nationals, lies about 30 miles off the western coast of Turkey. Its jagged ridge of scrub-covered mountains rises steeply out of the Aegean Sea. Before the Christian era, the island was home to thick oak forests and productive vineyards. Its reputation as a health destination dates back 25 centuries, when Greeks traveled to the island to soak in the hot springs near Therma. In the 17th century, Joseph Georgirenes, the bishop of Ikaria, described its residents as proud people who slept on the ground. “The most commendable thing on this island,” he wrote, “is their air and water, both so healthful that people are very long-lived, it being an ordinary thing to see persons in it of 100 years of age.”

Seeking to learn more about the island’s reputation for long-lived residents, I called on Dr. Ilias Leriadis, one of Ikaria’s few physicians, in 2009. On an outdoor patio at his weekend house, he set a table with Kalamata olives, hummus, heavy Ikarian bread and wine. “People stay up late here,” Leriadis said. “We wake up late and always take naps. I don’t even open my office until 11 a.m. because no one comes before then.” He took a sip of his wine. “Have you noticed that no one wears a watch here? No clock is working correctly. When you invite someone to lunch, they might come at 10 a.m. or 6 p.m. We simply don’t care about the clock here.”

Pointing across the Aegean toward the neighboring island of Samos, he said: “Just 15 kilometers over there is a completely different world. There they are much more developed. There are high-rises and resorts and homes worth a million euros. In Samos, they care about money. Here, we don’t. For the many religious and cultural holidays, people pool their money and buy food and wine. If there is money left over, they give it to the poor. It’s not a ‘me’ place. It’s an ‘us’ place.”

Ikaria’s unusual past may explain its communal inclinations. The strong winds that buffet the island — mentioned in the “Iliad” — and the lack of natural harbors kept it outside the main shipping lanes for most of its history. This forced Ikaria to be self-sufficient. Then in the late 1940s, after the Greek Civil War, the government exiled thousands of Communists and radicals to the island. Nearly 40 percent of adults, many of them disillusioned with the high unemployment rate and the dwindling trickle of resources from Athens, still vote for the local Communist Party. About 75 percent of the population on Ikaria is under 65. The youngest adults, many of whom come home after college, often live in their parents’ home. They typically have to cobble together a living through small jobs and family support.

Leriadis also talked about local “mountain tea,” made from dried herbs endemic to the island, which is enjoyed as an end-of-the-day cocktail. He mentioned wild marjoram, sage (flaskomilia), a type of mint tea (fliskouni), rosemary and a drink made from boiling dandelion leaves and adding a little lemon. “People here think they’re drinking a comforting beverage, but they all double as medicine,” Leriadis said. Honey, too, is treated as a panacea. “They have types of honey here you won’t see anyplace else in the world,” he said. “They use it for everything from treating wounds to curing hangovers, or for treating influenza. Old people here will start their day with a spoonful of honey. They take it like medicine.”

Over the span of the next three days, I met some of Leriadis’s patients. In the area known as Raches, I met 20 people over 90 and one who claimed to be 104. I spoke to a 95-year-old man who still played the violin and a 98-year-old woman who ran a small hotel and played poker for money on the weekend.

On a trip the year before, I visited a slate-roofed house built into the slope at the top of a hill. I had come here after hearing of a couple who had been married for more than 75 years. Thanasis and Eirini Karimalis both came to the door, clapped their hands at the thrill of having a visitor and waved me in. They each stood maybe five feet tall. He wore a shapeless cotton shirt and a battered baseball cap, and she wore a housedress with her hair in a bun. Inside, there was a table, a medieval-looking fireplace heating a blackened pot, a nook of a closet that held one woolen suit coat, and fading black-and-white photographs of forebears on a soot-stained wall. The place was warm and cozy. “Sit down,” Eirini commanded. She hadn’t even asked my name or business but was already setting out teacups and a plate of cookies. Meanwhile, Thanasis scooted back and forth across the house with nervous energy, tidying up.

The couple were born in a nearby village, they told me. They married in their early 20s and raised five children on Thanasis’s pay as a lumberjack. Like that of almost all of Ikaria’s traditional folk, their daily routine unfolded much the way Leriadis had described it: Wake naturally, work in the garden, have a late lunch, take a nap. At sunset, they either visited neighbors or neighbors visited them. Their diet was also typical: a breakfast of goat’s milk, wine, sage tea or coffee, honey and bread. Lunch was almost always beans (lentils, garbanzos), potatoes, greens (fennel, dandelion or a spinachlike green called horta) and whatever seasonal vegetables their garden produced; dinner was bread and goat’s milk. At Christmas and Easter, they would slaughter the family pig and enjoy small portions of larded pork for the next several months.

During a tour of their property, Thanasis and Eirini introduced their pigs to me by name. Just after sunset, after we returned to their home to have some tea, another old couple walked in, carrying a glass amphora of homemade wine. The four nonagenarians cheek-kissed one another heartily and settled in around the table. They gossiped, drank wine and occasionally erupted into laughter.

Dr. Ioanna Chinou, a professor at the University of Athens School of Pharmacy, is one of Europe’s top experts on the bioactive properties of herbs and natural products. When I consulted her about Ikarians’ longevity, she told me that many of the teas they consume are traditional Greek remedies. Wild mint fights gingivitis and gastrointestinal disorders; rosemary is used as a remedy for gout; artemisia is thought to improve blood circulation. She invited me to give her samples and later tested seven of the most commonly used herbs on Ikaria. As rich sources of polyphenols, they showed strong antioxidant properties, she reported. Most of these herbs also contained mild diuretics. Doctors often use diuretics to treat hypertension — perhaps by drinking tea nightly, Ikarians have gently lowered their blood pressure throughout their lives.

Meanwhile, my colleagues Gianni Pes and Michel Poulain set out to track down the island’s 164 residents who were over 90 as of 1999, starting in the municipality of Raches. They found that 75 nonagenarians were still alive. Then, along with additional researchers, they fanned out across the island and asked 35 elderly subjects a battery of lifestyle questions to assess physical and cognitive functioning: How much do you sleep? Did you ever smoke? They asked them to get up and down from a chair five times and recorded how long it took them to walk 13 feet. To test mental agility, the researchers had subjects recall a series of items and reproduce geometric shapes.

Pes and Poulain were joined in the field by Dr. Antonia Trichopoulou of the University of Athens, an expert on the Mediterranean diet. She helped administer surveys, often sitting in village kitchens to ask subjects to reconstruct their childhood eating habits. She noted that the Ikarians’ diet, like that of others around the Mediterranean, was rich in olive oil and vegetables, low in dairy (except goat’s milk) and meat products, and also included moderate amounts of alcohol. It emphasized homegrown potatoes, beans (garbanzo, black-eyed peas and lentils), wild greens and locally produced goat milk and honey.

As I knew from my studies in other places with high numbers of very old people, every one of the Ikarians’ dietary tendencies had been linked to increased life spans: low intake of saturated fats from meat and dairy was associated with lower risk of heart disease; olive oil — especially unheated — reduced bad cholesterol and raised good cholesterol. Goat’s milk contained serotonin-boosting tryptophan and was easily digestible for older people. Some wild greens had 10 times as many antioxidants as red wine. Wine — in moderation — had been shown to be good for you if consumed as part of a Mediterranean diet, because it prompts the body to absorb more flavonoids, a type of antioxidant. And coffee, once said to stunt growth, was now associated with lower rates of diabetes, heart disease and, for some, Parkinson’s. Local sourdough bread might actually reduce a meal’s glycemic load. You could even argue that potatoes contributed heart-healthy potassium, vitamin B6 and fiber to the Ikarian diet. Another health factor at work might be the unprocessed nature of the food they consume: as Trichopoulou observed, because islanders eat greens from their gardens and fields, they consume fewer pesticides and more nutrients. She estimated that the Ikarian diet, compared with the standard American diet, might yield up to four additional years of life expectancy.

Of course, it may not be only what they’re eating; it may also be what they’re not eating. “Are they doing something positive, or is it the absence of something negative?” Gary Taubes asked when I described to him the Ikarians’ longevity and their diet. Taubes is a founder of the nonprofit Nutrition Science Initiative and the author of “Why We Get Fat” (and has written several articles for this magazine). “One explanation why they live so long is they eat a plant-based diet. Or it could be the absence of sugar and white flour. From what I know of the Greek diet, they eat very little refined sugar, and their breads have been traditionally made with stone-ground wheat.”

Following the report by Pes and Poulain, Dr. Christina Chrysohoou, a cardiologist at the University of Athens School of Medicine, teamed up with half a dozen scientists to organize the Ikaria Study, which includes a survey of the diet of 673 Ikarians. She found that her subjects consumed about six times as many beans a day as Americans, ate fish twice a week and meat five times a month, drank on average two to three cups of coffee a day and took in about a quarter as much refined sugar — the elderly did not like soda. She also discovered they were consuming high levels of olive oil along with two to four glasses of wine a day.

Chrysohoou also suspected that Ikarians’ sleep and sex habits might have something to do with their long life. She cited a 2008 paper by the University of Athens Medical School and the Harvard School of Public Health that studied more than 23,000 Greek adults. The researchers followed subjects for an average of six years, measuring their diets, physical activity and how much they napped. They found that occasional napping was associated with a 12 percent reduction in the risk of coronary heart disease, but that regular napping — at least three days weekly — was associated with a 37 percent reduction. She also pointed out a preliminary study of Ikarian men between 65 and 100 that included the fact that 80 percent of them claimed to have sex regularly, and a quarter of that self-reported group said they were doing so with “good duration” and “achievement.”

During our time on Ikaria, my colleagues and I stayed at Thea Parikos’s guesthouse, the social hub of western Ikaria. Local women gathered in the dining room at midmorning to gossip over tea. Late at night, after the dinner rush, tables were pushed aside and the dining room became a dance floor, with people locking arms and kick-dancing to Greek music.

Parikos cooked the way her ancestors had for centuries, giving us a chance to consume the diet we were studying. For breakfast, she served local yogurt and honey from the 90-year-old beekeeper next door. For dinner, she walked out into the fields and returned with handfuls of weedlike greens, combined them with pumpkin and baked them into savory pies. My favorite was a dish made with black-eyed peas, tomatoes, fennel tops and garlic and finished with olive oil that we dubbed Ikarian stew.

Despite her consummately Ikarian air, Parikos was actually born in Detroit to an American father and an Ikarian mother. She had attended high school, worked as a real estate agent and married in the United States. After she and her husband had their first child, she felt a “genetic craving” for Ikaria. “I was not unhappy in America,” she said. “We had good friends, we went out to dinner on the weekends, I drove a Chevrolet. But I was always in a hurry.”

When she and her family moved to Ikaria and opened the guesthouse, everything changed. She stopped shopping for most groceries, instead planting a huge garden that provided most of their fruits and vegetables. She lost weight without trying to. I asked her if she thought her simple diet was going to make her family live longer. “Yes,” she said. “But we don’t think about it that way. It’s bigger than that.”

Although unemployment is high — perhaps as high as 40 percent — most everyone has access to a family garden and livestock, Parikos told me. People who work might have several jobs. Someone involved in tourism, for example, might also be a painter or an electrician or have a store. “People are fine here because we are very self-sufficient,” she said. “We may not have money for luxuries, but we will have food on the table and still have fun with family and friends. We may not be in a hurry to get work done during the day, so we work into the night. At the end of the day, we don’t go home to sit on the couch.”

Parikos was nursing a mug of coffee. Sunlight sifted in through the window shades; the waves of the nearby Aegean could be barely heard over the din of breakfast. “Do you know there’s no word in Greek for privacy?” she declared. “When everyone knows everyone else’s business, you get a feeling of connection and security. The lack of privacy is actually good, because it puts a check on people who don’t want to be caught or who do something to embarrass their family. If your kids misbehave, your neighbor has no problem disciplining them. There is less crime, not because of good policing, but because of the risk of shaming the family. You asked me about food, and yes, we do eat better here than in America. But it’s more about how we eat. Even if it’s your lunch break from work, you relax and enjoy your meal. You enjoy the company of whoever you are with. Food here is always enjoyed in combination with conversation.”

In the United States, when it comes to improving health, people tend to focus on exercise and what we put into our mouths — organic foods, omega-3’s, micronutrients. We spend nearly $30 billion a year on vitamins and supplements alone. Yet in Ikaria and the other places like it, diet only partly explained higher life expectancy. Exercise — at least the way we think of it, as willful, dutiful, physical activity — played a small role at best.

Social structure might turn out to be more important. In Sardinia, a cultural attitude that celebrated the elderly kept them engaged in the community and in extended-family homes until they were in their 100s. Studies have linked early retirement among some workers in industrialized economies to reduced life expectancy. In Okinawa, there’s none of this artificial punctuation of life. Instead, the notion of ikigai — “the reason for which you wake up in the morning” — suffuses people’s entire adult lives. It gets centenarians out of bed and out of the easy chair to teach karate, or to guide the village spiritually, or to pass down traditions to children. The Nicoyans in Costa Rica use the term plan de vida to describe a lifelong sense of purpose. As Dr. Robert Butler, the first director of the National Institute on Aging, once told me, being able to define your life meaning adds to your life expectancy.

The healthful plant-based diet that Seventh-day Adventists eat has been associated with an extra decade of life expectancy. It has also been linked to reduced rates of diabetes and heart disease. Adventists’ diet is inspired by the Bible — Genesis 1:29. (“And God said: ‘Behold, I have given you every herb yielding seed . . . and every tree, in which is the fruit of a tree yielding seed; to you it shall be for food.’ ”) But again, the key insight might be more about social structure than about the diet itself. While for most people, diets eventually fail, the Adventists eat the way they do for decades. How? Adventists hang out with other Adventists. When you go to an Adventist picnic, there’s no steak grilling on the barbecue; it’s a vegetarian potluck. No one is drinking alcohol or smoking. As Nicholas Christakis, a physician and social scientist at Harvard, found when examining data from a long-term study of the residents of Framingham, Mass., health habits can be as contagious as a cold virus. By his calculation, a Framingham individual’s chances of becoming obese shot up by 57 percent if a friend became obese. Among the Adventists we looked at, it was mostly positive social contagions that were in circulation.

Ask the very old on Ikaria how they managed to live past 90, and they’ll usually talk about the clean air and the wine. Or, as one 101-year-old woman put it to me with a shrug, “We just forget to die.” The reality is they have no idea how they got to be so old. And neither do we. To answer that question would require carefully tracking the lifestyles of a study group and a control group for an entire human lifetime (and then some). We do know from reliable data that people on Ikaria are outliving those on surrounding islands (a control group, of sorts). Samos, for instance, is just eight miles away. People there with the same genetic background eat yogurt, drink wine, breathe the same air, fish from the same sea as their neighbors on Ikaria. But people on Samos tend to live no longer than average Greeks. This is what makes the Ikarian formula so tantalizing.

If you pay careful attention to the way Ikarians have lived their lives, it appears that a dozen subtly powerful, mutually enhancing and pervasive factors are at work. It’s easy to get enough rest if no one else wakes up early and the village goes dead during afternoon naptime. It helps that the cheapest, most accessible foods are also the most healthful — and that your ancestors have spent centuries developing ways to make them taste good. It’s hard to get through the day in Ikaria without walking up 20 hills. You’re not likely to ever feel the existential pain of not belonging or even the simple stress of arriving late. Your community makes sure you’ll always have something to eat, but peer pressure will get you to contribute something too. You’re going to grow a garden, because that’s what your parents did, and that’s what your neighbors are doing. You’re less likely to be a victim of crime because everyone at once is a busybody and feels as if he’s being watched. At day’s end, you’ll share a cup of the seasonal herbal tea with your neighbor because that’s what he’s serving. Several glasses of wine may follow the tea, but you’ll drink them in the company of good friends. On Sunday, you’ll attend church, and you’ll fast before Orthodox feast days. Even if you’re antisocial, you’ll never be entirely alone. Your neighbors will cajole you out of your house for the village festival to eat your portion of goat meat.

Every one of these factors can be tied to longevity. That’s what the $70 billion diet industry and $20 billion health-club industry do in their efforts to persuade us that if we eat the right food or do the right workout, we’ll be healthier, lose weight and live longer. But these strategies rarely work. Not because they’re wrong-minded: it’s a good idea for people to do any of these healthful activities. The problem is, it’s difficult to change individual behaviors when community behaviors stay the same. In the United States, you can’t go to a movie, walk through the airport or buy cough medicine without being routed through a gantlet of candy bars, salty snacks and sugar-sweetened beverages. The processed-food industry spends more than $4 billion a year tempting us to eat. How do you combat that? Discipline is a good thing, but discipline is a muscle that fatigues. Sooner or later, most people cave in to relentless temptation.

As our access to calories has increased, we’ve decreased the amount of physical activity in our lives. In 1970, about 40 percent of all children in the U.S. walked to school; now fewer than 12 percent do. Our grandparents, without exercising, burned up about five times as many calories a day in physical activity as we do. At the same time, access to food has exploded.

Despite the island’s relative isolation, its tortuous roads and the fierce independence of its inhabitants, the American food culture, among other forces, is beginning to take root in Ikaria. Village markets are now selling potato chips and soda, which in my experience is replacing tea as the drink of choice among younger Ikarians. As the island’s ancient traditions give way before globalization, the gap between Ikarian life spans and those of the rest of the world seems to be gradually disappearing, as the next generations of old people become less likely to live quite so long.

The big aha for me, having studied populations of the long-lived for nearly a decade, is how the factors that encourage longevity reinforce one another over the long term. For people to adopt a healthful lifestyle, I have become convinced, they need to live in an ecosystem, so to speak, that makes it possible. As soon as you take culture, belonging, purpose or religion out of the picture, the foundation for long healthy lives collapses. The power of such an environment lies in the mutually reinforcing relationships among lots of small nudges and default choices. There’s no silver bullet to keep death and the diseases of old age at bay. If there’s anything close to a secret, it’s silver buckshot.

I called Moraitis a few weeks ago from my home in Minneapolis. Elpiniki died in the spring at age 85, and now he lives alone. He picked up the phone in the same whitewashed house that he’d moved into 35 years ago. It was late afternoon in Ikaria. He had worked in his vineyard that morning and just awakened from a nap. We chatted for a few minutes, but then he warned me that some of his neighbors were coming over for a drink in a few minutes and he’d have to go. I had one last question for him. How does he think he recovered from lung cancer?

“It just went away,” he said. “I actually went back to America about 25 years after moving here to see if the doctors could explain it to me.”

I had heard this part of the story before. It had become a piece of the folklore of Ikaria, proof of its exceptional way of life. Still, I asked him, “What happened?”

“My doctors were all dead.”


This article is adapted from new material being published in the second edition of “Blue Zones,” by Dan Buettner, out next month from National Geographic.

Editor: Dean Robinson


This article has been revised to reflect the following correction:

Correction: October 28, 2012

An article on Page 36 this weekend about the reasons people on the Greek Island of Ikaria live long lives misstates the period when fasting is practiced by the island’s inhabitants. They fast before Orthodox feast days, not during Orthodox feast days.

Icaria - Long Lived People and No Dimentia! Real Balance Global Wellness Services, LLC.
In all, we found 13 likely contributors to Ikarian longevity. The formula below may be the closest you’ll get to the fountain of youth:

Graze on greens More than 150 varieties of wild greens grow on Ikaria. Some have more than ten times the level of antioxidants in red wine.

Sip herbal teas Steeping wild mint, chamomile, or other herbs in hot water is a lifelong, daily ritual. Many teas lower blood pressure, which decreases the risk of heart disease and dementia.

Throw out your watch Ikarians don’t worry about time. Work gets done when it gets done. This attitude lowers stress, which reduces the risk of everything from arthritis to wrinkles.

Nap daily Ikarian villages are ghost towns during the afternoon siesta, and science shows that a regular 30-minute nap decreases the risk of heart attack.

Walk where you’re going Mountainous terrain and a practice of walking for transport mean that every trip out of the house is a mini workout.

Phone a friend With the island’s rugged terrain, family and village support have been key to survival. Strong social connections are proven to lower depression, mortality, and even weight.

Drink goat’s milk Most Ikarians over 90 have drunk goat’s milk their whole lives. It is rich in a blood-pressure-lowering hormone called tryptophan as well as antibacterial compounds.

Maintain a Mediterranean diet Around the world, people who most faithfully stick to this region’s diet—a regimen high in whole grains, fruits, vegetables, olive oil, and fish—outlive people who don’t by about six years. The Ikarian version features more potatoes than grains (because they grew better in the mountains) and more meat than fish (because the sea was a day’s journey away).

Enjoy some Greek honey The local honey contains antibacterial, anticancer and anti-inflammatory properties. (Unfortunately, the health benefits of Ikarian honey do not extend to American honey, as far as we know.)

Open the olive oil Ikaria’s consumption of olive oil is among the world’s highest. Residents drizzle antioxidant-rich extra-virgin oil over food after cooking, which preserves healthful properties in the oil that heat destroys.

Grow your own garden (or find farmers’ markets) Fruits and vegetables eaten soon after picking are higher in compounds that decrease the risk of cancer and heart disease.

Get religion Ikarians observe Greek Orthodox rituals, and regular attendance at religious services (of any kind ) has been linked to longer life spans.

Bake bread The island’s sourdough bread is high in complex carbohydrates and may improve glucose metabolism and stave off diabetes.

What We Can Learn from the Greek-Island Diet—and What We Already Know | Mother Jones
The Ikarians down two to 3.5 glasses of wine each day—including, apparently, the occasional glass with breakfast. Coffee is indulged at the rate of two to three cups daily. And the afternoon nap, apparently, is observed near universally. "People stay up late here," a local doctor tells Buettner. "We wake up late and always take naps. I don't even open my office until 11 a.m. because no one comes before then."

Other lessons will seem austere to many Americans. Per capita US meat consumption averages to a little more than half a pound a day. Ikarians, by contrast, eat meat on average just five times per month. And Ikarians eat about a quarter as much sugar as Americans do, and very little processed food (although that is beginning to change.) The overall diet is classic Mediterranean. Buettner describes a typical couple's daily food routine:

[A] breakfast of goat's milk, wine, sage tea or coffee, honey and bread. Lunch was almost always beans (lentils, garbanzos), potatoes, greens (fennel, dandelion or a spinachlike green called horta) and whatever seasonal vegetables their garden produced; dinner was bread and goat’s milk. At Christmas and Easter, they would slaughter the family pig and enjoy small portions of larded pork for the next several months.

So they're eating a low-meat, relatively seafood-rich, nutrient-dense diet with plenty of greens and (he emphasizes elsewhere) olive oil. Buettner also mentions a warm beverage they drink which he translates as "mountain tea," "made from dried herbs endemic to the island," a rotating, seasonal list that includes wild marjoram, sage, mint, and dandelion leaves. Buetnner had samples of the greens tested in a lab, and they proved to be "rich sources of polyphenols" with "strong antioxidant properties."

Sociodemographic and Lifestyle Statistics of Oldest Old People (>80 Years) Living in Ikaria Island: The Ikaria Study
PubMed Central, Table 2: Cardiol Res Pract. 2011; 2011: 679187. Published online 2011 February 24. doi:

Ikaria Greece Longevity Secrets - Business Insider

http://www.hellenicjcardiol.com/archive/full_text/2011/5/2011_5_479.pdf
 
Schmeisser S, Priebe S, Groth M, et al. Neuronal ROS Signaling Rather Than AMPK/Sirtuin-Mediated Energy Sensing Links Dietary Restriction to Lifespan Extension. Molecular Metabolism. ScienceDirect.com - Molecular Metabolism - Neuronal ROS Signaling Rather Than AMPK/Sirtuin-Mediated Energy Sensing Links Dietary Restriction to Lifespan Extension

Dietary restriction (DR) extends lifespan and promotes metabolic health in evolutionary distinct species. DR is widely believed to promote longevity by causing an energy deficit leading to increased mitochondrial respiration.

We here show that inhibitors of mitochondrial complex I promote physical activity, stress resistance as well as lifespan of C. elegans despite normal food uptake, i.e. in the absence of DR. However, complex I inhibition does not further extend lifespan in dietarily restricted nematodes, indicating that impaired complex I activity mimics DR. Promotion of longevity due to complex I inhibition occurs independently of known energy sensors, including DAF-16/ FoxO, as well as AAK-2/ AMPK and SIR-2.1/ sirtuins, or both. Instead and consistent with the concept of mitohormesis, complex I inhibition transiently increases mitochondrial formation of reactive oxygen species (ROS) that activate PMK-1/ p38 MAP kinase and SKN-1/ NRF-2. Interference with this retrograde redox signal as well as ablation of two redox-sensitive neurons in the head of the worm similarly prevents extension of lifespan.

These findings unexpectedly indicate that DR extends organismal lifespan through transient neuronal ROS signaling rather than sensing of energy depletion, providing unexpected pharmacological options to promote exercise capacity and healthspan despite unaltered eating habits.
 
Kuehn BM. US Longevity Falls Short vs That of Peer Countries. JAMA. 2013;309(6):534. JAMA Network | JAMA | US Longevity Falls Short vs That of Peer Countries

Although the United States spends more on health care than any other country, US residents live shorter and less healthy lives than do people in other developed nations, according to a new report (http://tinyurl.com/a4yzn3o) from the National Research Council and the Institute of Medicine. Moreover, the report found that the mortality gap is growing, in large part because of a disproportionately higher rate of early deaths among individuals in the United States before their 50th birthday.

The report compares US health outcomes and mortality data with data from 16 peer countries, including Australia, Austria, Canada, Denmark, Finland, France, Germany, Italy, and Japan. The panel that drafted the report found that the life expectancy of residents of the United States was shorter than that of residents of almost all the peer countries. They also found that the health disparities persisted across health conditions and extended to high-income and highly educated groups.

These results suggest that health disparities between lower-income US individuals and minorities and higher-income and white individuals do not fully explain the US mortality gap.

The United States did, however, fare better than other countries on longevity after age 75 years.

Much of the differences in longevity were related to early deaths. For example, the United States had the highest infant mortality rate, and disproportionately fewer US children live until their fifth birthday. Violence and injuries are large contributors to deaths among children, adolescents, and young adults in the United States. Steven H. Woolf, MD, MPH, chair of the panel and professor of family medicine at Virginia Commonwealth University, noted that US individuals were 7 times more likely to die as a result of violence and 20 times more likely to be killed by a gun than people living in peer countries.

Residents of the United States were also less healthy than many of their counterparts in other countries on several measures. For example, US teens had the highest pregnancy rate and they are more likely to develop a sexually transmitted disease. People living in the United States also had the second highest rate of HIV infection and the highest rate of AIDS. The United States also had the highest rates of obesity across age groups and the highest rate of diabetes among adults aged 20 years and older. Older adults in the United States are also more likely to report physical activity limitations.

Woolf said that cultural and social differences in the countries may account for some of the disparity in longevity. He noted that although the United States spends more on health care than other countries, many peer countries spend much more than the United States on various social programs that may contribute to good health and longevity.

“Social policies are probably to blame for part of this problem,” he said.
 
People who live on the Greek island of Ikaria are known to have remarkably high life expectancies, and researchers have been studying them carefully to learn why. Now a new report suggests that one reason may be the coffee they drink.


Siasos G, Oikonomou E, Chrysohoou C, et al. Consumption of a boiled Greek type of coffee is associated with improved endothelial function: The Ikaria Study. Vascular Medicine. Consumption of a boiled Greek type of coffee is associated with improved endothelial function: The Ikaria Study

Objective: The association of coffee consumption with cardiovascular disease remains controversial. Endothelial function is associated with cardiovascular risk. We examined the association between chronic coffee consumption and endothelium function in elderly inhabitants of the island of Ikaria.

Methods: The analysis was conducted on 142 elderly subjects (aged 66–91 years) of the Ikaria Study. Endothelial function was evaluated by ultrasound measurement of flow-mediated dilation (FMD). Coffee consumption was evaluated based on a food frequency questionnaire and was categorized as ‘low’ (< 200 ml/day), ‘moderate’ (200–450 ml/day), or ‘high’ (> 450 ml/day).

Results: From the subjects included in the study, 87% consumed a boiled Greek type of coffee. Moreover, 40% had a ‘low’, 48% a ‘moderate’ and 13% a ‘high’ daily coffee consumption. There was a linear increase in FMD according to coffee consumption (‘low’: 4.33 ± 2.51% vs ‘moderate’: 5.39 ± 3.09% vs ‘high’: 6.47 ± 2.72%; p = 0.032). Moreover, subjects consuming mainly a boiled Greek type of coffee had a significantly higher FMD compared with those consuming other types of coffee beverages (p = 0.035).

Conclusions: Chronic coffee consumption is associated with improved endothelial function in elderly subjects, providing a new connection between nutrition and vascular health.
 
Longevity
On Beyond 100

Our genes harbor many secrets to a long and healthy life. And now scientists are beginning to uncover them.
http://ngm.nationalgeographic.com/2013/05/longevity/hall-text
 
Levy BR, Slade MD, Kunkel SR, Kasl SV. Longevity increased by positive self-perceptions of aging. J Pers Soc Psychol 2002;83(2):261-70.

This research found that older individuals with more positive self-perceptions of aging, measured up to 23 years earlier, lived 7.5 years longer than those with less positive self-perceptions of aging. This advantage remained after age, gender, socioeconomic status, loneliness, and functional health were included as covariates. It was also found that this effect is partially mediated by will to live. The sample consisted of 660 individuals aged 50 and older who participated in a community-based survey, the Ohio Longitudinal Study of Aging and Retirement (OLSAR). By matching the OLSAR to mortality data recently obtained from the National Death Index, the authors were able to conduct survival analyses. The findings suggest that the self-perceptions of stigmatized groups can influence longevity.
 

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Hypothalamus Is Important For The Development Of Whole-Body Ageing

Almond-Sized Brain Region is Control Centre for Ageing
Almond-Sized Brain Region is Control Centre for Ageing – Phenomena: Not Exactly Rocket Science

Of special and particular note is the role of GnRH.

Ageing is a result of gradual and overall functional deteriorations across the body; however, it is unknown whether an individual tissue primarily works to mediate the ageing progress and control lifespan.

Here we show that the hypothalamus is important for the development of whole-body ageing in mice, and that the underlying basis involves hypothalamic immunity mediated by I?B kinase-?(IKK-?), nuclear factor ?B (NF-?B) and related microglia–neuron immune crosstalk.

Several interventional models were developed showing that ageing retardation and lifespan extension are achieved in mice by preventing ageing-related hypothalamic or brain IKK-? and NF-?B activation.

Mechanistic studies further revealed that IKK-? and NF-?B inhibit gonadotropin-releasing hormone(GnRH) to mediate ageing-related hypothalamic GnRH decline, and GnRH treatment amends ageing-impaired neurogenesis and decelerates ageing.

In conclusion, the hypothalamus has a programmatic role in ageing development via immune–neuroendocrine integration, and immune inhibition or GnRH restoration in the hypothalamus/brain represent two potential strategies for optimizing lifespan and combating ageing-related health problems.

Zhang G, Li J, Purkayastha S, et al. Hypothalamic programming of systemic ageing involving IKK-?, NF-?B and GnRH. Nature;advance online publication. http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12143.html
 
Slowing the Aging Process

Why is it that within a homogeneous population of the same species, some individuals live three times as long as others? This question has stumped scientists for centuries.

Reducing mitochondrial output increases lifespan in mice and nematode worms. Researchers found that reduced expression of a protein important for mitochondrial protein production triggered the mitochondrial stress response and increased lifespan. A few known drugs affect this pathway, raising the possibility of designing longevity-enhancing therapies.

It’s well known that mitochondria are linked to health. Some evidence suggests that inhibiting mitochondrial function can be harmful—as in the case of diabetes or obesity—but earlier data from nematodes and fruit flies also suggest a link to lifespan increase. The latest findings are a step toward untangling one of the current debates in the field—whether inhibiting mitochondrial function is detrimental or beneficial.


Houtkooper RH, Mouchiroud L, Ryu D, et al. Mitonuclear protein imbalance as a conserved longevity mechanism. Nature 2013;497(7450):451-7. http://www.nature.com/nature/journal/v497/n7450/full/nature12188.html

Longevity is regulated by a network of closely linked metabolic systems. We used a combination of mouse population genetics and RNA interference in Caenorhabditis elegans to identify mitochondrial ribosomal protein S5 (Mrps5) and other mitochondrial ribosomal proteins as metabolic and longevity regulators. MRP knockdown triggers mitonuclear protein imbalance, reducing mitochondrial respiration and activating the mitochondrial unfolded protein response. Specific antibiotics targeting mitochondrial translation and ethidium bromide (which impairs mitochondrial DNA transcription) pharmacologically mimic mrp knockdown and extend worm lifespan by inducing mitonuclear protein imbalance, a stoichiometric imbalance between nuclear and mitochondrially encoded proteins.

This mechanism was also conserved in mammalian cells. In addition, resveratrol and rapamycin, longevity compounds acting on different molecular targets, similarly induced mitonuclear protein imbalance, the mitochondrial unfolded protein response and lifespan extension in C. elegans. Collectively these data demonstrate that MRPs represent an evolutionarily conserved protein family that ties the mitochondrial ribosome and mitonuclear protein imbalance to the mitochondrial unfolded protein response, an overarching longevity pathway across many species.
 
Mao Z, Zhao L, Pu L, Wang M, Zhang Q, He DZ. How well can centenarians hear? PLoS One 2013;8(6):e65565. PLOS ONE: How Well Can Centenarians Hear?

With advancements in modern medicine and significant improvements in life conditions in the past four decades, the elderly population is rapidly expanding. There is a growing number of those aged 100 years and older. While many changes in the human body occur with physiological aging, as many as 35% to 50% of the population aged 65 to 75 years have presbycusis. Presbycusis is a progressive sensorineural hearing loss that occurs as people get older. There are many studies of the prevalence of age-related hearing loss in the United States, Europe, and Asia. However, no audiological assessment of the population aged 100 years and older has been done. Therefore, it is not clear how well centenarians can hear. We measured middle ear impedance, pure-tone behavioral thresholds, and distortion-product otoacoustic emission from 74 centenarians living in the city of Shaoxing, China, to evaluate their middle and inner ear functions. We show that most centenarian listeners had an "As" type tympanogram, suggesting reduced static compliance of the tympanic membrane. Hearing threshold tests using pure-tone audiometry show that all centenarian subjects had varying degrees of hearing loss. More than 90% suffered from moderate to severe (41 to 80 dB) hearing loss below 2,000 Hz, and profound (>81 dB) hearing loss at 4,000 and 8,000 Hz. Otoacoustic emission, which is generated by the active process of cochlear outer hair cells, was undetectable in the majority of listeners. Our study shows the extent and severity of hearing loss in the centenarian population and represents the first audiological assessment of their middle and inner ear functions.
 
Interesting! My MIL turned 100 in February. Up until 2 years ago (Age 98) I always said she could hear thru walls. She had amazing hearing and mysteriously she lost almost all her hearing in her right ear. We had her examined and scanned but nothing showed. I would have to ask my wife if that is correct or not, but I don't think they found anything. She still hears very well in her left ear, but has this 90% loss in her rt ear.

Me on the other hand, at 71 have lost the hearing in my rt ear and about 50% in my left ear. I can function somewhat with high dollar digital hearing aids. To you young whipper snappers, wear ear protection when working with tools and engines and guns, cutting the grass, etc.

All the years working in a body shop plus the racing of cars and motorcycles pretty much wrecked my ears. The final blow to my rt ear was an old Cadillac muffler loaded with fuel, ignited when the engine backfired. Things were scary quiet for a few days.

As they say "Live and learn" but some of us were just plain dumb in the early days.
 
Martin-Montalvo A, Mercken EM, Mitchell SJ, et al. Metformin improves healthspan and lifespan in mice. Nat Commun 2013;4. http://www.nature.com/ncomms/2013/130730/ncomms3192/full/ncomms3192.html

Metformin is a drug commonly prescribed to treat patients with type 2 diabetes. Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, while a higher dose (1% w/w) was toxic.

Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake. At a molecular level, metformin increases AMP-activated protein kinase activity and increases antioxidant protection, resulting in reductions in both oxidative damage accumulation and chronic inflammation.

Our results indicate that these actions may contribute to the beneficial effects of metformin on healthspan and lifespan. These findings are in agreement with current epidemiological data and raise the possibility of metformin-based interventions to promote healthy aging.
 
Increased Lifespan and Slowing of Aging after Genetic Reduction of mTOR Expression

Highlights
• In mammals, decreased mTOR expression produces a profound increase in lifespan
• Reduced mTOR expression results in lower rates of spontaneous tumor formation
• Age-related benefits of reduced mTOR expression are tissue specific

Recent evidence suggests that mTOR may regulate lifespan in a wide range of organisms, including mammals. Unfortunately, few good mouse models of reduced mTOR activity exist.

Here, Finkel and colleagues characterize a hypomorphic model of mTOR expression. Mice expressing reduced levels of mTOR live significantly longer than their wild-type littermates.

Of note, while overall lifespan is extended, careful phenotyping of this model demonstrates that reducing mTOR activity slows the rate of tissue and organ aging in a segmental fashion.


Wu JJ, Liu J, Chen Edmund B, et al. Increased Mammalian Lifespan and a Segmental and Tissue-Specific Slowing of Aging after Genetic Reduction of mTOR Expression. Cell Reports. Cell Reports - Increased Mammalian Lifespan and a Segmental and Tissue-Specific Slowing of Aging after Genetic Reduction of mTOR Expression

We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic (mTOR”/”) alleles are viable but express mTOR at approximately 25% of wild-type levels. These animals demonstrate reduced mTORC1 and mTORC2 activity and exhibit an approximately 20% increase in median survival.

While mTOR”/” mice are smaller than wild-type mice, these animals do not demonstrate any alterations in normalized food intake, glucose homeostasis, or metabolic rate. Consistent with their increased lifespan, mTOR”/” mice exhibited a reduction in a number of aging tissue biomarkers. Functional assessment suggested that, as mTOR”/” mice age, they exhibit a marked functional preservation in many, but not all, organ systems. Thus, in a mammalian model, while reducing mTOR expression markedly increases overall lifespan, it affects the age-dependent decline in tissue and organ function in a segmental fashion.
 
Gaming improves multitasking skills
Study reveals plasticity in age-related cognitive decline.
Gaming improves multitasking skills : Nature News & Comment

A study published this week in Nature convincingly shows that if a game is tailored to a precise cognitive deficit, in this case multitasking in older people, it can indeed be effective.

The study found that a game called NeuroRacer can help older people to improve their capacity to multitask — and the effect seems to carry over to tasks in everyday life and is still there after six months. The study also shows how patterns of brain activity change as those cognitive skills improve.
 
http://www.nytimes.com/2013/09/29/nyregion/a-nightly-dinner-out-thats-like-therapy.html

A Nightly Dinner Out That’s Like Therapy
By COREY KILGANNON

It never fails, Harry Rosen said on Wednesday evening as he enjoyed another fine meal by himself in another top-rated Manhattan restaurant.

“Maybe because I’m eating alone at my age, people at other tables start conversations,” he said.

Yes, he tells them, he lives alone, in a modest studio apartment on West 57th Street in Manhattan, and he always eats dinner out, always orders the fish.

“They always ask my age, and I often lie and tell them I’m 90,” he said. “If I tell them my real age, it becomes the whole subject of conversation and makes it look like I’m looking for attention, which I’m not.”

Mr. Rosen is 103 but he doesn’t look a day over 90. His mother died at 53 and his father at 70, but he says he feels fine and has had no major operations or health problems.

“I read in a newspaper column a long time ago that the key to a long life is sleeping on your back, so I always did that,” said Mr. Rosen, who often finds that his bill has been paid by those friendly diners. Not that he needs it. He made a bundle with his office supply company and is spending it — $100 a night, on average — on dinners out.

Much of his work involved wooing clients over lunch and dinner, so after retiring a few years back because of hearing loss, he continued to put on a fine work suit every afternoon, grab his satchel, and head out to hail a yellow cab to one of his favorite restaurants. Café Boulud perhaps, on East 76th Street, or Boulud Sud near Lincoln Center, or Avra Estiatorio on East 48th Street.

“I haven’t eaten dinner home in many years,” said Mr. Rosen, who tried singles groups and other activities after his wife of 70 years, Lillian, died five years ago, when she was 95.

But nothing brought him the comfort of a fine restaurant.

“It’s my therapy, it lifts my spirits,” he said Wednesday evening while examining the menu with a magnifying glass at David Burke Townhouse on East 61st Street.

Twice a week, a server there greets him, walks him to his usual corner table and brings his regular glass of chardonnay, his appetizer of raw salmon and tuna, and then the swordfish, skin removed, with vegetables specially puréed for his dentures to handle.

“The food and the ambience, it’s my therapy — it gives me energy,” he said.

Mr. Rosen has lived long enough to see New York City fill with fine restaurants. In a city of foodies, he may be the oldest.

Call it payback for the meager meals he ate growing up in Russia, where as a boy, he recalled, he marched with protesters during the Russian Revolution. He and his family fled the pogroms, came through Ellis Island and moved into a railroad apartment on Pitt Street on the Lower East Side. By the time he was 11, young Harry’s meals improved to pickled herring sold from barrels on the street, and he worked as a delivery boy for pennies before taking a job at an office supply company.

“I knew it was the business for me, the same way you know you’re in love with a woman,” Mr. Rosen said. He started Radio Center Stationery in Midtown — back then, “you could look down Sixth Avenue and not see a single office building” — whose staff of 50 included his sons, Stan and Jerry. They regularly join him for dinner.

The deals to land clients like Walt Disney, ABC and the Hearst Corporation were made in top restaurants, Mr. Rosen said. You don’t win over the likes of Jack Linsky, the founder of Swingline staplers, by dining at dumps.

But as much as any fine meal, Mr. Rosen savors the memories of his deal making, including landing J. C. Penney with a great price on notepads, and fighting back from bankruptcy as computers encroached upon the industry.

On Wednesday, he backed up these recollections with photos and documents stored meticulously in folder boxes in his apartment.

“They’re called Pendaflex folders,” he said. “I was the first one in the industry to recognize they’d be a big seller.”

Mr. Rosen said he would like to find a regular dining companion. A recent six-month fling with a 90-year-old woman he met at synagogue did not work out.

“I’m still open to meeting someone,” he said, his eyes twinkling as he prepared to order coffee and dessert. “I still have the desire. That’s what counts.”
 

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