[Special Feature: The Future of Japanese "Food"] Yasumichi Arai: What is the "Diet" that Makes Longevity Possible?

As longevity increases worldwide, the average life expectancy for Japanese men has reached 81.64 years, and 87.74 years for women (2020 Ministry of Health, Labour and Welfare Abridged Life Tables). Longevity is expected to continue increasing gradually, and by around 2040-2045, it is estimated that the average life expectancy for women in long-lived countries such as Japan, Hong Kong, South Korea, and Spain will exceed 90 years. In order to spend a life that is significantly longer than that of our grandparents' generation with a sense of purpose and happiness, it is important to make our healthy life expectancy as long as possible. At the Keio University School of Medicine Center for Supercentenarian Medical Research, we have been working on academic surveys of elderly people aged 100 and over (centenarians) for a total of 30 years, including the era of its predecessor, the Department of Geriatric Medicine. We are researching factors that contribute to healthy longevity from a wide range of perspectives, including biomedical sciences, genetics, and social psychology.

"Diet" plays an important role not only in the onset of lifestyle-related diseases such as hypertension, obesity, and diabetes, but also in maintaining skeletal muscle and physical functions essential for independence in daily life. To realize a long-lived society where everyone can rejoice in living a long life, it will be necessary to develop a food environment that supports efforts to lead an independent life until the end of one's life through the practice of a "diet" based on scientific evidence. In this article, I would like to consider the "diet" that makes longevity possible based on the findings of centenarian research.

First, what kind of health management is necessary to survive the era of 100-year lifespans? In a survey we conducted jointly with the Tokyo Metropolitan Institute of Gerontology, 97% of the 304 centenarians studied had some form of chronic disease; even centenarians were not free from illness. However, there were few histories of serious illnesses such as cerebral infarction, heart disease, or cancer. In particular, only 6.0% had diabetes, which was less than half the rate of the general elderly population. This is thought to be related to the low prevalence of obesity and overeating since youth. Overseas studies have also reported low rates of diabetes and obesity, which can be said to be a common characteristic of centenarians. Among centenarians, the proportions of dyslipidemia and hypertension are also lower than in the general elderly population, and the smoking rate is also low. Therefore, having few risk factors for atherosclerosis seems to be the first step toward healthy longevity.

Most centenarians are independent in their daily lives until their mid-90s, but only about 20% are still independent at age 100. Subsequent follow-up surveys showed that the group of about 20% who were independent had a high probability of reaching age 105, and some even lived to 110 to become supercentenarians. Due to their rarity (according to the 2015 census, a ratio of 1 in 870,000 of the total population), research that actually visits and surveys supercentenarians is extremely limited worldwide. At the Center for Supercentenarian Medical Research, led by former Invited Professor Nobuyoshi Hirose, we conducted a nationwide recruitment effort spanning over 10 years and finally established a supercentenarian cohort of a scale that allows for epidemiological research.

As a result of medical investigations, it was found that the reason supercentenarians remain independent in daily life even at age 100 is related to high cognitive function and resistance to frailty. Frailty refers to a state in which the functions of organs throughout the body decline with age and stress tolerance decreases. It is diagnosed by five signs: weight loss (5% or more of body weight in 6 months), muscle weakness, easy fatigability (tiredness), slow walking speed, and decreased physical activity. In other words, it is important to maintain skeletal muscle function to avoid becoming frail.

Comparative studies of centenarians and supercentenarians have also revealed the blood characteristics of ultra-long-lived people who maintain health even beyond age 100. As a result of measuring substances in the blood related to aging (biomarkers), the concentrations of NT-proBNP and albumin were strongly associated with survival rates after age 100. NT-proBNP is a molecule secreted by the heart that rises when the heart is under stress; it is a biomarker commonly used in routine clinical practice as a guide for the diagnosis and treatment of heart failure. Although centenarians have few heart diseases such as myocardial infarction, they cannot escape the decline in cardiac function due to aging, and NT-proBNP concentrations were higher than in the general elderly population. However, supercentenarians had significantly lower NT-proBNP concentrations at age 100 compared to other centenarians. In other words, it was considered that the decline in cardiac function due to aging is slower, and people with lower NT-proBNP live longer even beyond age 100.

On the other hand, albumin is a protein synthesized in the liver and is the most abundant protein among plasma proteins. In our research, a decrease in albumin concentration was consistently associated with an increase in mortality across a wide range of age groups, from elderly people aged 85 and over to supercentenarians. Albumin decreases in states of malnutrition or liver dysfunction and is associated with edema and frailty; it is a biomarker measured in health checkups for the elderly. Furthermore, albumin is known for its protective effects against inflammation and oxidative stress, and its importance in healthy longevity was reaffirmed.

From research on centenarians and supercentenarians, who are models of healthy longevity, it has become clear that preventing obesity and diabetes from a young age to suppress the progression of atherosclerosis, and preventing dementia and frailty and slowing the aging of the heart after entering old age, is the health method for the era of 100-year lifespans. So, what kind of diet did centenarians actually use to achieve healthy longevity? In collaboration with the Keio University Hospital Catering and Nutrition Office, we conducted a three-day dietary record survey of 34 centenarians. On average, the energy intake of centenarians was about 30 kcal/kg of body weight, and it was found that they secured energy and protein intake levels comparable to those of adults. In terms of food items, intake of dairy products, sweets/sugars, and fruits was high, while intake of grains, meat, fish, and fats/oils was low. A tendency to prefer sweet and soft foods was observed, suggesting that declines in taste and oral function influence dietary habits at age 100.

The Mediterranean diet is rich in scientific evidence from epidemiological surveys and intervention trials as a healthy longevity diet. It uses plenty of olive oil and features high intake of vegetables, fruits, nuts, legumes, unrefined grains such as whole wheat, and fish, while intake of red meat and processed meat is low. In terms of nutrients, fat intake is high overall, but intake of saturated fatty acids and cholesterol, which are associated with the onset of heart disease, is low, and the proportion of omega-3 unsaturated fatty acids is high. Intake of vitamin E and polyphenols, which have strong antioxidant effects, is high, and it is thought to extend lifespan by having preventive effects against diabetes, atherosclerosis, cardiovascular disease, and cancer overall. However, it is a low-protein diet, and its preventive effect against frailty and sarcopenia is not clear.

Although it does not match the Mediterranean diet in terms of scientific evidence, the traditional Japanese diet (Washoku) is also attracting attention as a healthy longevity diet. Washoku uses rice as the staple food and includes a variety of food materials such as fish, meat, vegetables, and soybeans as "one soup and three dishes," plus fruit. It uses many food materials and contains many components effective for maintaining health. However, Washoku often uses miso, soy sauce, and salt as seasonings, and how to suppress salt intake is a challenge.

We focused on the relationship between fish consumption and healthy longevity and, with the cooperation of about 500 elderly people aged 85 and over living in Tokyo, investigated the relationship between dietary habits and health indicators (cognitive function, grip strength, walking function, carotid atherosclerosis, etc.) using a diet history questionnaire. As a result, those with higher intakes of EPA and DHA, which are abundant in fish, maintained better walking function, which is a diagnostic item for frailty. Furthermore, since EPA and DHA intake was also associated with inflammation markers and oxidative stress markers in the blood, it was suggested that EPA and DHA intake may suppress chronic inflammation and lead to the prevention of frailty.

To maintain skeletal muscle function and prevent frailty, it is also important to increase protein intake. Protein intake is also important for maintaining albumin concentration in the blood. The Dietary Reference Intakes for Japanese (2020 edition) also raised the target protein intake for the elderly from the perspective of preventing frailty and malnutrition*1. Foods containing high-quality protein with a good balance of amino acids include meat, seafood, dairy products, eggs, and soybeans/soybean products, but no clear results have been obtained as to which foods lead to the extension of healthy life expectancy. At present, it is recommended to consume these foods in a balanced manner to secure the protein necessary for maintaining skeletal muscle.

Prevention of dementia is also important for achieving healthy longevity. The Mediterranean diet involves high intake of ingredients rich in folic acid, B vitamins, and vitamin E, such as green-yellow vegetables, nuts, fruits, and whole grains, and low intake of red meat, which suppresses saturated fatty acid intake. Therefore, it is thought to be effective in preventing dementia, but the evidence is not yet fully established. Since risk factors for atherosclerosis such as diabetes and hypertension increase the risk of not only vascular dementia but also Alzheimer's disease, it is recommended to strive for a well-balanced diet while being careful not to consume too many calories or too much salt.

Considering the survey results of centenarians and supercentenarians, it seems that a "diet" suited to the life stage plays a major role in achieving healthy longevity. For the working generation, dietary guidance for metabolic syndrome measures aimed at preventing atherosclerotic diseases will also be important for extending healthy life expectancy. Upon reaching old age, it is important to take high-quality protein from meat, fish, and soybean products in a balanced way to maintain skeletal muscle, and to consume vegetables and fruits rich in vitamins as a measure against oxidative stress associated with aging. In anticipation of the aging population, the Dietary Reference Intakes for Japanese (2020 edition) established intake targets for nutrients and other substances by dividing the elderly age categories into two: 65-74 years and 75 years and older, in consideration of frailty prevention and lifestyle-related disease prevention. However, in older generations, individual differences in physical strength, activity levels, and the functions of organs such as the kidneys and liver become larger, making it difficult to group people by chronological age. For example, in elderly people with decreased kidney function, a high-protein diet may actually increase the load on the body. Therefore, in the future, a system that recommends nutritional intake suited to an individual's physical condition, using indicators such as functional age (reflecting physical strength, cognitive function, physical activity, etc.) and biological age (reflecting the degree of aging of cells and organs), is desired.

When considering "diet" in a long-lived society, it is also necessary to consider the decline in chewing and swallowing functions associated with aging. Elderly people with decreased occlusal force find it difficult to consume meat, seafood, and raw vegetables, and their intake of nutrients such as protein, vitamins A and C, dietary fiber, EPA, and DHA tends to decrease. Recently, foods in forms suited to the degree of swallowing and chewing disorders, such as Smile Care Foods, have been developed, and it will be necessary to find ways to expand the range of food intake.

"Diet" is not only an aspect of nutritional intake but also a daily pleasure. From that perspective, considering changes in taste associated with aging, the development of ingredients and cooking methods that elderly people find delicious, and the "dietary" situation, such as who they eat with, are also important aspects. The problem of eating alone is not limited to the elderly, but health hazards due to malnutrition tend to be more serious in the elderly, and especially for men, eating alone carries a high risk of leading to depression. Although there are restrictions during the COVID-19 pandemic, the role of communal eating involving family, friends, and neighbors will also be important.

In order for the international community to work together to address the aging population progressing on a global scale, the United Nations adopted the "United Nations Decade of Healthy Ageing 2021-2030." Over these 10 years, it aims to improve the lives of the elderly, their families, and local communities through coordination between governments, civil society, international organizations, academia, the media, and the private sector. When considering the "diet" that makes longevity possible, it will be necessary for industry, government, academia, and the community to work together on everything from clarifying the mechanisms of biological aging and the onset of dementia and frailty, and the preventive effects of various nutrients against them, to developing foods that suit the tastes of the elderly and providing food systems that involve the community. The Center for Supercentenarian Medical Research will continue to contribute to the establishment of a scientific foundation that supports a "long-lived society where everyone can rejoice in living a long life" as a hub for interdisciplinary longevity research.

*1 Ministry of Health, Labour and Welfare "Dietary Reference Intakes for Japanese" (2020 edition)