Okinawan sea grapes, or ‘umi budo’.
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.
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
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
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).
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.
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).
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.