Monday, June 22, 2015

The Okinawa health advantage


Documentaries and books on the subject of diet and longevity love to focus on the super long life-spans of the people of Okinawa (e.g. here, here and here) - the folk on this Japanese island seem to have it all figured, so we are led to think. Out of curiosity I thought I'd have a gander at the latest research notes on the issue. As is the tendency, things become much more nuanced when you dive in to the detail. My cuttings and pastings are below but the take-away messages are:

  • The longevity advantage for people who are born in Okinawa today has disappeared when compared to mainland Japan.
  • The advantage is most obvious for people born before WWII.
  • Calorie/Dietary restriction (abbreviated to 'CR' or 'DR') may have played a significant role (from my experience calorie restriction increases the desire for nutritionally rich foodstuffs).
  • One question raised is whether severe calorie restriction resulted in worse health outcomes for future generations? (Le Bourg). 
  • Or is the onset of the Western diet (highly processed foods) the more likely culprit?
  • As to the effects of CR, we should await the outcome of more controlled, comprehensive studies e.g. CALERIE study.
Whereas some commentators focus solely on diet, others point out the healthy social lifestyles of many Okinawans, and they would also seem to be fairly physically independent and active. There is the question of whether their diet is optimised to their genes, or vice-versa.

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Quotes from various studies:

 From 'Comments on Dietary Restriction, Okinawa Diet and Longevity by Natalia S. Gavrilova* and Leonid A. Gavrilov. . Gerontology. 2012 Apr; 58(3): 221–223.
  • A relatively low infectious load combined with low calorie consumption in the past seems to be responsible for exceptional longevity in Okinawa. Although severe caloric restriction seems not to be a necessary condition for life extension in humans, DR should not be dismissed as a valid way of delaying atherosclerosis and eventually extending the life span of nonobese individuals.
  • A study of older Okinawans demonstrated that they appear to have undergone a mild form of prolonged DR for about half their adult lives. It was also shown that the composition of a traditional Okinawan diet is similar to a Mediterranean diet and a DASH (Dietary Approaches to Stop Hypertension) diet, which are known to be beneficial to human health later in life. Indeed, Okinawans have low mortality from aging-related diseases later in life.
  • It should be noted that this longevity advantage in Okinawa is observed only for generations born before World War II. Younger generations of Okinawans are losing their longevity advantage compared to mainland Japanese. Moreover, life expectancy at birth for men in Okinawa is now lower than the country average.
  • After World War II, BMI and energy intake of Okinawans were gradually increasing while energy expenditure was decreasing so that between the 1960s and 1970s adult Okinawans ceased to be in a caloric restriction state. This process was accompanied by a spread of cardiovascular diseases. Similar processes were well described in epidemiological studies of Japanese migrants to America. Current demographic and nutritional data suggest that the remarkable Okinawan longevity is now a phenomenon of the past.
  • Side effects of DR include: a decrease in sex hormones with subsequent bone thinning, cold sensitivity, slower wound healing, psychological changes including depression and anxiety.
  • One potential problem of low calorie consumption may be increased susceptibility to pathogens reported in animal studies. It is interesting that the Okinawa archipelago apparently had a low infectious load in the past. This conclusion follows from a relatively low infant mortality in 1900 and 1940.
  • ... that detrimental effects of obesity may have an exceptionally long time range. However, slender body build, consistent with low calorie consumption, did not give any longevity advantage compared to medium body build. Thus, severe caloric restriction is not always a necessary condition for living to 100. In this regard, we would agree with Le Bourg that in contemporary populations DR should be used first for improving the health status of obese people although DR should not be dismissed as a valid approach to extending life span in nonobese individuals.
Other interesting snippets on the topic of longevity:


Search for Mechanisms of Exceptional Human Longevity by Natalia S. Gavrilov and Leonid A. Gavrilov, Rejuvenation Res. 2010 Apr; 13(2-3): 262–264.
  • ...our findings presented here suggest that in American families siblings born to younger mothers (before age 25) have almost twice the odds to live to 100 years, even after age 75. This corresponds well with the earlier findings on laboratory mice.
  • The second study explored whether people living to 100 and beyond were any different in physical characteristics from their peers at their middle age (30 years). ... It was found that the “stout” body build (being in the heaviest 15% of control population) was negatively associated with longevity and persons with slender and medium body build had higher chances of survival to 100. Both farming occupation and having large number of children (4+) at age 30 significantly increased the chances of exceptional longevity.
In a later paper by the same authors:

  • An important factor of survival to advanced age is childhood farm residence—a result found in our earlier study .
  • Existing literature on U.S. mortality and our own results based on the within-family approach show that month of birth may be a significant predictor of mortality not only during childhood but also in later life (they show increased longevity for people born in the second half of the year).
  • ..It is also important to note that parental longevity turned out to be one of the strongest predictors of survival to age 100. ... This study also suggests that a significant portion of life span advantage for siblings of centenarians may be related to better lifestyle and living conditions rather than pure genetic effects only (otherwise, wives of centenarians would not benefit much from husbands' longevity).
Optimal body weight for health and longevity: bridging basic, clinical, and population research by Luigi Fontan and Frank B Hu,  Aging Cell. 2014 Jun; 13(3): 391–400.
  • The continuing controversy regarding overweight and mortality has caused a great deal of confusion not only among the general public but also among health professionals. This controversy underscores the many methodological challenges in analyses of the relationship between BMI and mortality, including reverse causation, confounding by smoking, effect modification by age, and imperfect measures of adiposity. However, evidence for the adverse impact of overweight and moderate obesity on chronic disease incidence is overwhelming and indisputable. In addition, mounting evidence indicates that being overweight significantly reduces the probability of healthy aging. Many well-conducted studies in large cohorts have shown that being overweight does increase the risk of premature mortality.
Centenarians and supercentenarians: a black swan. Emerging social, medical and surgical problems by Marco Vacante,1 Velia D’Agata,2 Massimo Motta,1 Giulia Malaguarnera,3 Antonio Biondi,4 Francesco Basile,4 Michele Malaguarnera,corresponding author2 Caterina Gagliano,5 Filippo Drago,2 and Salvatore Salamone2, BMC Surg. 2012; 12(Suppl 1): S36. 
  • On Factors that influence the longevity: Many studies suggested that some factors are important to longevity in centenarians: 1) heredity, role of specific genes and family history  2) general health and lifestyle, i.e. weight, diet, amount of physical exercise, smoking habits 3) education level 4) personality. The largest population of centenarians are widowed women . The Okinawa Centenarians Study (OCS) has shown several different factors that have contributed to the large number of centenarians there. These factors are: 1) a diet based mainly on grains, fish and vegetables instead of meat, eggs, and dairy products; 2) low-stress lifestyles, compared to the mainland inhabitants of Japan; 3) caring community and active work until an older age than the average age in other countries; 5) a strong role of spirituality, with involvement in spiritual matters and prayer that ease the mind of stress and problems. Human longevity is due to genetics, age, sex, ethnicity and environment of the study population. Whether prolonged caloric restriction (CR) increases average or maximum lifespan or promotes a more youthful physiology in humans at advanced ages is not yet known. However, available epidemiological evidence indicates that CR may already have contributed to an extension of average and maximum life span in older Okinawans and appears to have lowered risk for age associated chronic diseases in other human populations.
  • Pointing out some key differences between people who make it to 100 vs those who get to 110 (Supercentenarians): The supercentenarians display an elevated percentual occurrence of alterations which do not have a deterministic role in the survival: (cataract, osteoporosis, bone fractures, etc.), and a low prevalence of more significant, chronic degenerative pathologies. Generally they reach 100 years of age in good health, and only after 105 years of age start to manifest age-dependent alterations with high variability [9]. Usually their death cause is not correlated to the typical pathologies of aged people, such as cancer, stroke, myocardial infarction, etc.. The decreased prevalence of various pathologies widely documented in the centenarians, as compared to the elderly, seems to be present also in the supercentenarians, compared to the centenarians. Even the dementia of various clinical aspects, which is the only disease condition more frequent in the elderly than in the centenarians seems to be of lower prevalence in the supercentenarians, as compared to the centenarians.
  • One study reported Medicare data indicating that, in 2000, there were 32,920 centenarians and that, of these, 0.3% were age 110 and older.
From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition? by Katarzyna Szarc vel Szic, Ken Declerck, Melita Vidaković, and Wim Vanden Berghe,  Clin Epigenetics. 2015; 7(1): 33.
  • .. it is unknown to what extent inflammaging or longevity is controlled by epigenetic events in early life. Today, human diet is believed to have a major influence on both the development and prevention of age-related diseases. Most plant-derived dietary phytochemicals and macro- and micronutrients modulate oxidative stress and inflammatory signaling and regulate metabolic pathways and bioenergetics that can be translated into stable epigenetic patterns of gene expression. Therefore, diet interventions designed for healthy aging have become a hot topic in nutritional epigenomic research. Increasing evidence has revealed that complex interactions between food components and histone modifications, DNA methylation, non-coding RNA expression, and chromatin remodeling factors influence the inflammaging phenotype and as such may protect or predispose an individual to many age-related diseases. Remarkably, humans present a broad range of responses to similar dietary challenges due to both genetic and epigenetic modulations of the expression of target proteins and key genes involved in the metabolism and distribution of the dietary constituents
  • It is not yet clear whether aging is a cause or consequence following purely epigenetic changes ...
  • Although epigenetic modifications previously were thought to be fixed during development and maintained over the lifetime, more recent research provides evidence that epigenetic mechanisms allow rapid adaptations to a changing environment and are responsive to signaling cascades.
  • The phenotype of an individual is the result of complex ongoing gene-environment interactions in the present, past, and ancestral environments, responsible for lifelong remodeling of our epigenomes. In recent years, several studies have demonstrated that disruption of epigenetic mechanisms can alter immune function and that epimutations not only contribute to certain cancers but also to lifestyle diseases such as type 2 diabetes, allergies, cardiovascular disease, and rheumatoid arthritis, as well as unhealthy aging. Various replication-dependent and -independent epigenetic mechanisms are involved in developmental programming, a lifelong intertwined process of monitoring and responding to environmental changes, and the transmission of transgenerational effects. It is likely that improved understanding of epigenetic processes will allow us to manipulate the epigenome which represents a reversible source of biological variation. We believe that herein resides a great potential for chemoprevention, alleviation of chronic inflammatory disorders, and healthy aging. Much attention is currently focused on the modulation of hyper/hypomethylation of key inflammatory genes by dietary factors as an effective approach to chronic inflammatory disease management and general health benefits. In this respect, ‘Let food be your epigenetic medicine’ could represent a novel interpretation of what Hippocrates said twenty-five centuries ago. As such, it will be a challenge for future nutritional research to identify novel epigenetic targets that promote healthy aging. Given several encouraging trials, prevention and therapy of age- and lifestyle-related diseases by individualized tailoring of optimal epigenetic diets or supplements are conceivable.

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