In the northern Okinawa village of Ogimi, a stone marker displays the declaration of village elders that reads  "at eighty you are merely a youth, at ninety if the ancestors invite you into heaven, ask them to wait until you are one hundred... and then you might consider it."

In the northern Okinawa village of Ogimi, a stone marker displays the declaration of village elders that reads "at eighty you are merely a youth, at ninety if the ancestors invite you into heaven, ask them to wait until you are one hundred... and then you might consider it."

The Okinawa Centenarian Study

Established in 1975, the OCS and its over 1000 participants have made important contributions to understanding the aging process and longevity.

To put the healthy aging achievements of Okinawa in perspective, many of the centenarians that the OCS has interviewed were born near the end of the 19th century. At that time, average life expectancy was only slightly greater than 40 years of age for both men and women in Japan. That these robust centenarians lived decades longer and survived infectious diseases, natural disasters, and a World War that ravaged their island home is remarkable.

Sources: Japan Ministry of Health Labor Welfare 2017; Centers for Disease Control and Prevention 2017

Sources: Japan Ministry of Health Labor Welfare 2017; Centers for Disease Control and Prevention 2017

The significance of Okinawa’s health phenomenon can be appreciated by considering a typical age-associated disease and its impact upon a typical city of 100,000 inhabitants in Okinawa, Japan and the United States. For coronary heart disease (CHD)—the leading cause of death in the United States—if the city was located in Okinawa, about 3 times fewer males and more than 4 times fewer females would have died from this ailment in a typical year, than if this was a city in the United States. That is a striking difference.


Methods

Today, the study includes interviews and examinations of 1000+ centenarians and hundreds of younger elders in their seventies, eighties, and nineties. The OCS looks for underlying commonalities in their diets, exercise habits, genetics, psychological and spiritual practices, and social and behavioral patterns. By studying exceptionally-aged individuals in a multidisciplinary biological, social, and cultural context, the OCS seeks insight into processes promoting disease prevention and healthy life extension.

General Methods of the OCS:

Small but spunky super-centenarian (>110 years of age)!

Small but spunky super-centenarian (>110 years of age)!

  • Population-based study

  • Cross-sectional, Longitudinal, Case-control

  • Age validation

  • Geriatric exam with past medical history, social history,  family history, health habits, anthropometry, electrocardiogram, psychosocial/cognitive tests

  • Family pedigree

  • Evaluation of Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL)

  • Blood draw and analysis


Key Findings

The OCS has found that cigar-smoking, whiskey swilling hundred-year olds who effortlessly trek across mountain ranges to be myth. Rather population-based research demonstrates wide differences in the centenarian population from functional independence to high levels of disease and disability. In Okinawa, about one third of centenarians were found to be functionally independent, about one third needed major assistance with activities of daily living (ADL), and about one third were very ill and disabled (Sanabe et al. 1977; Suzuki et al. 1995 PMID: 7500549).

Although high levels of disability are present in a significant portion of these exceptional survivors, an important caveat is that most centenarians seem to be healthier than the average person throughout their lives, and remain functionally independent until their mid-nineties (Willcox et al. 2008 PMID: 19038835). Below, we discuss three important aspects of the Okinawan lifestyle—their diet, social practices, and genetics.


the okinawan diet

Much of the longevity advantage in Okinawa is thought to be related to the traditional Okinawan diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products.

Willcox et al.  J Am Coll Nutr.  2009

Willcox et al. J Am Coll Nutr. 2009

Prior to World War 2, the traditional Okinawan diet was a mixed plate of Chinese, Japanese and South East Asian influences. In the Okinawan language, this fusion was often referred to as “champuru” or “chample,” which means “mixture.” The staple food of traditional Okinawan cuisine was many varieties of colorful sweet potatoes, in contrast to the polished white rice of their mainland Japanese counterparts. In addition to steamed sweet potatoes, meals regularly included large varieties of simmered or steamed green leafy, yellow root vegetables, and soy-based products such as tofu, miso soup and miso flavorings. These staples were often accompanied with smaller servings of fish, lean meats such as pork, and tropical fruit such as shikuwasa (Citrus depressa). Okinawans favored bonito flavored broths for seasoning and used herbs and spices such as turmeric or mugwort liberally in place of salt. Okinawans also celebrated various festivals on a regular basis that supplemented their diet with a variety of different foods including rice, kombu seaweed, various meats and other seafoods.

Willcox et al.  J Am Coll Nutr.  2009

Willcox et al. J Am Coll Nutr. 2009

In fact, the traditional Okinawan diet shares many characteristics with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress.

Willcox  et al. Ann NY Acad Sci.  2007

Willcox et al. Ann NY Acad Sci. 2007

In Okinawa, the low-calorie, phytonutrient-rich and nutritionally dense food choices, the healthy eating habits, and high levels of physical activity resulted in a naturally calorically restricted population without malnutrition. In the traditional dietary habits, there was a focus on small portion sizes and not eating until completely full. Even now a common saying among Okinawan elderly is hara hachi bu (eat until only 80 percent full). We estimate that Okinawans prior to the 1960s consumed 10-15% fewer calories than would normally be required per caloric guidelines (Willcox et al. 2007 PMID: 17986602). When faced with a persistent energy deficit, mammals adapt by becoming more energy efficient, producing less heat and converting a higher proportion of food into usable energy. A host of other metabolic adaptations occur that confer longevity. These changes are commonly observed in animal studies of “caloric restriction” (CR) and this is the only consistently reproducible manner of increasing mean and maximum lifespan in animal experiments, other than select genetic manipulations. (Fontana et al. 2010 PMID: 20395504).

Additionally, the traditional Okinawan diet appears to be a rich source of foods that may mimic the biological effects of CR, acting as caloric restriction “mimetics.” CR-mimetics are compounds that provide the physiological benefit of CR without the need for restriction of calories through multiple mechanisms, including reduced oxidative stress. In the Okinawan language, a common parlance is “nuchi gusui,” which can best be translated as “let food be your medicine.” This reflects the cultural context wherein the distinction between food and medicine blurs in Okinawa and deeper analyses reveals that many of the traditional foods, herbs, or spices in the Okinawan diet have medicinal properties, which are under investigation (Willcox & Willcox 2014 PMID: 24462788).

IMG_9490.jpg

Nuchi gusui

“Let food be your medicine”

Commonly consumed items that play dual roles as both traditional medicines and foods include sweet potatoes (pulp, skin and leaves), bitter melon, multiple green leafy vegetables, ginger, turmeric, mugwort (Artemisia vulgaris), peppers (Piper hancei) and carotenoid-rich marine foods (such as seaweeds), among others. Many of these foods have anti-aging properties by reducing oxidative stress and inflammation, two key factors that underlie the development of most age-related diseases.

In the Post-War period, rice supplanted the sweet potato as the staple food and the volume of food products imported into Okinawa, as throughout the rest of Japan, has increased rapidly in line with the progress of globalization. In modern Okinawa, people enjoy a widely varied diet, although large generational differences now stand out with elders sticking closer to the traditional diet. A recent dietary survey of Okinawan centenarians revealed the most frequently consumed food was white rice. However, there was a striking abundance and variety of low-caloric density vegetables and legumes (including soy-products or tofu), indicative of traditional dietary habits (unpublished data).


social

Several unique social practices seem to give the current generation of Okinawan elders a longevity edge.  Although support networks in Japan are typically thought to be mainly family-centered, support networks in Okinawa also center around friends and neighbors. It is thought the tight settlement pattern in Okinawan villages and high rates of autonomy of Okinawan elders may encourage them to stay employed longer and have greater levels of social contact. Interestingly, there is no word for “retirement” in the Okinawan language.

In more recent times, maintaining social support networks have become even more important for older people in depopulated rural villages because reliable support from younger family members can no longer be taken for granted. The Okinawan elderly have found ways to enhance interdependence among themselves through friendships and associations. Informal visiting, sharing of work tasks, reciprocal exchanges of gifts, information and other items help to create tight-knit communities that form strong social ties and supportive relationships between the elderly. Some additional unique cultural practices are listed below:

The “Gateball Club”

The “Gateball Club”

MOAI

One cultural tradition that has encouraged supportive relationships is forming a moai. A moai is an informal group of people who meet regularly, share common interests, and support each other. In times of need, moai provide financial and emotional support that give members greater peace of mind that their “tribe” has their back.

IKIGAI

Okinawans each embrace their own “ikigai,” which means “sense of purpose in life.” An ikigai gives their lives purpose, responsibility and a clear reason to begin each day.

For some, this allows for a high level of social integration. A good example of this is the Basho-fu weaving of Ogimi village in northern Okinawa. In this unique style of weaving, the time and labor-intensive process of cleaning the fibers and spooling the thread is performed mainly by groups of older women. In addition to providing social opportunities, it allows these women to be respected and active members of the local economy as well as supplement their income (Willcox et al. 2007 PMID: 17318443).

RELIGION AND SPIRITUALITY

religion.png

The interconnected role of religion, spirituality, aging and health in the lives of older Okinawan women has yet to be adequately explored, but likely plays another important role in their remarkable health. Okinawa remains the only contemporary society in which women actually lead the mainstream, publicly funded religion. In Okinawa, elderly women’s active engagement in religious roles may have an important role in reducing depression and associated rates of suicide (Willcox and Katata 2000; [Japanese]). Rates of suicide for elderly Okinawan women have, for many years, been among the lowest in East Asia, a region known for high rates of suicide among older women (Pritchard & Baldwin, 2002 PMID: 11942931).


GEnetics

A pilot genome-wide association study (GWAS) investigated characteristics of the Okinawan genome. When compared to other ethnic populations in human genetic databases, analysis showed that Okinawans cluster strongly with East Asians with little outside mixture (Bendjilali et al. 2014). These data support the hypothesis that Okinawans, while related to Japanese and Chinese are also genetically distinct.

A pilot genome-wide association study (GWAS) investigated characteristics of the Okinawan genome. When compared to other ethnic populations in human genetic databases, analysis showed that Okinawans cluster strongly with East Asians with little outside mixture (Bendjilali et al. 2014). These data support the hypothesis that Okinawans, while related to Japanese and Chinese are also genetically distinct.

Genetics has long been a focus of the OCS. Longevity is a complex trait and to survive another 15 or more years beyond the average, people may need a relatively rare, or exceptional combination of environmental, behavioral and genetic factors, and that many of these factors run in families. Okinawans have traditionally married within their own villages and geographic isolation has limited gene inflow resulting in less genetic variability in Okinawans that in other Japanese (Bendjilali et al. 2014 PMID: 24444611). These factors can favor clustering of genetic variants, leading to extreme phenotypes, such as longevity (Willcox et al. 2006 PMID: 22253498).

Historically, genetic research in this area relied upon studies utilizing identical and fraternal twins. Findings from twin studies have suggested that environment/lifestyle accounts for about two-thirds of lifespan, while genetics accounts for one third (Ljungquist et al. 1998 PMID: 9823748). Other twin studies have also come up with estimates in the 25-30 percent range (McGue et al. 1993 PMID: 8227991; Herskind et al. 1996 PMID: 8786073). Other scientists, using multiple methods, have argued that the contribution from genetics for predicting very long life is closer to one half  (Perls et al. 2002 PMID: 12028221).

The OCS performed the first study of candidate human longevity genes and found that Okinawan in their 90s and centenarians had higher prevalence of anti-inflammatory type-2 human leukocyte antigen (HLA) alleles and a lower prevalence of pro-inflammatory alleles (Takata  et al . 1987)

The OCS performed the first study of candidate human longevity genes and found that Okinawan in their 90s and centenarians had higher prevalence of anti-inflammatory type-2 human leukocyte antigen (HLA) alleles and a lower prevalence of pro-inflammatory alleles (Takata et al. 1987)

Regarding genetic factors and longevity, in 1985, OCS investigators performed the first extensive study of centenarian pedigrees, finding more longevity among siblings in centenarian families than control families. Two decades later, with an enlarged data set, OCS investigators found that cumulative survival advantages for the centenarian sibling cohort increased over the life span such that female centenarian siblings had a 2.58-fold likelihood and male siblings a 5.43-fold likelihood, versus their birth cohorts, of reaching their 90s (Willcox et al. 2006 PMID: 16611700).

More recently, the OCS has focused on investigating the longevity-associated FOXO3 gene, which was identified as associated with human longevity by our team at the Kuakini Medical Center Honolulu Heart Program and the John A. Burns School of Medicine, University of Hawai‘i at Manoa (Willcox et al. 2008 PMID: 18765803).


The OCS Today

Today, the OCS continues its important research into longevity. The importance of our work is underscored by the recent changes in Okinawa, which have adversely affected healthy human aging. The younger generations are straying from the traditional diet in favor of processed and fast foods high in sodium and saturated fats. Traffic jams have become a regular aspect of island life as locals increasingly rely on cars for transportation, undercutting their physical activity.

Nonetheless, healthy aging is achievable and Okinawa provides ample evidence and lessons for exceptional longevity. Whether or not future generations of elderly continue the trend towards reduced disability and an extended health expectancy may well depend upon the lifestyle choices that individuals make in mid-life or earlier, particularly in diet and exercise. These gains will be coupled with the investments in preventive medicine, public health infrastructure and long-term care that societies make in the coming decades.

To this end, the OCS is committed to generating research aimed at promoting healthy human aging. Here are some of our current ongoing projects:


longevity Genes, telomeres and inflammation

In 2008, our team at Kuakini Medical Center Honolulu Heart Program identified variants in the FOXO3 gene to be associated with human longevity. More than a dozen independent studies of populations of diverse ancestry in multiple different countries have now confirmed and extended this finding. Based on research to date, FOXO3 is one of only two genes (the other longevity-associated gene is APOE) that have been replicated consistently across diverse human populations for association with reaching extreme old age (Morris et al. 2015 PMID: 25832544).

Davy et al.  JGBS,  2018

Davy et al. JGBS, 2018

Recently, the OCS published its findings that carriers of the longevity-associated version of the FOXO3 gene have minimal telomere shortening across different age groups in a cross-sectional study of Okinawans. Telomeres are protective caps at the ends of DNA that get shorter every time our cells divide, but keep our important DNA intact. Eventually, telomeres get too short with repeated cell divisions and cause our cells to age and stop functioning properly. Thus, telomeres can be thought of as the “biological aging clock” in every cell, and telomere biology is a fundamental mechanism of aging.

The OCS believes FOXO3 may protect against telomere attrition with age by reducing chronic oxidative stress and inflammation at the cellular level. This translates to a longer, and healthier human lifespan, particularly in the elderly. Additional research efforts are currently underway to investigate these important mechanisms that may tie telomere biology, different age-associated diseases, and FOXO3 genotype together.


chample study

The famous “Chample Study” was initiated in 2005 by Dr. Hidemi Todoriki originally to study the medicinal properties of Okinawa vegetables. Another phase included a dietary intervention in American civilian volunteers to investigate the effect of increased consumption of traditional Okinawan vegetables on human health (right images). The Chample Study has since evolved to educating children and families about balanced nutrition in an effort to improve dietary habits in younger generations in primary school. Indeed, early results show that higher nutrition knowledge in children and guardians are associated with higher vegetable intake (Asakura et al. 2017 PMID: 28576447).


Keys to Optimal Cognitive Aging (KOCOA) study

The KOCOA Study is an ongoing cohort study of healthy volunteers aged over 80 years old, living in Okinawa, Japan. The goal of the KOCOA Study is to examine key factors that could explain healthy cognitive aging. This is a collaborative study between the University of the Ryukyus Graduate School of Medicine in Okinawa, Japan led by Dr. Hiroko Dodge and the Layton Aging and Alzheimer’s Disease Center at Oregon Health & Science University in Portland, OR, USA. The KOCOA study utilizes a rich collection of nutrient markers including a full panel of plasma amino acids and food frequency questionnaire, metabolic assessments, inflammation markers and MRI.

See Publications for more information.