International collaborative research
１．5 Country Oldest Old Project (5COOP)
Research on centenarians is currently in progress not only in Japan, but also in the U.S.A., Italy, China, and other countries around the world. It is extremely important to accurately know the proportion of centenarians who need nursing care in their daily lives or who have dementia in each country, and to enable international comparisons, taking into account the countermeasures against aging societies all over the world. In previous centenarian studies, however, international comparisons were difficult because each country has different methods for measuring ADL and cognitive function.
In 2010, Dr. Jean-Merrie Robine, a French demographicist, organized an international comparative study on function, life expectancy. Called the 5 Country Oldest Old Project (5 COOP), the project involves researchers from France, Switzerland, Denmark, Sweden and Japan, and evaluates the ADL and cognitive functions of centenarians according to a common research protocol.
Dr. Yasuhiko Saito at the University Research Center, Nihon University is a representative of the project in Japan. In addition, the Graduate School of Human Sciences at Osaka University, Center for Supercentenarian Medical Research in Keio University School of Medicine, Okinawa International University and Tokyo Metropolitan Institute of Gerontology has also joined the collaborative project. Currently, Singapore, Taiwan, and Thailand are preparing for participation in the project from Asian countries with aging population.
Robine JM, Cheung SL, Saito Y, Jeune B, Parker MG, Herrmann FR. Centenarians today: new insights on selection from the 5-COOP study. Curr Gerontol Geriatr Res 2010; 2010: 120354. （PMID: 21423541; DOI: 10.1155/2010/120354）.
２．Leukocyte telomere length in centenarians: Collaboration with Newcastle University
Telomeres are a repetitive sequence located at the end of chromosomes.
Telomere length is thought to be an indicator of cellular aging, because they gradually become shorter each time cell division occurs. Based on epidemiological studies, it has been reported that the leukocyte telomere length is shortened with age and in cardiovascular disease / diabetic patients.
In collaboration with Prof. Thomas von Zglinicki of the Newcastle University Institute of Aging, world leader in telomere studies, we studied a total of 1,554 elderly people, including 684 centenarians (105–107 years of age) and their offspring and spouses, and the very old (85–99 years of age). Biomarkers were considered in the areas of anemia, glucose / lipid metabolism, major organ reserve (liver and renal function), inflammation, and cellular senescence (telomere length), which are biological regions considered to contribute to longevity. We analyzed the relationship between these and indicators of healthy longevity (life expectancy, ADL, cognitive function, and multimorbidity). Results showed that in the elderly in general, telomere length shortened with aging, but the offspring of centenarians thought to be genetically likely to reach 100 years old showed relatively long telomere length. Even when actual age was 80 years, telomere length was comparable to that of others in their 60s. Likewise, relatively long telomere length was retained even in semi-supercentenarians. In other words, we found that better maintenance of telomere length may be a familial contributing factor for healthy longevity.
Furthermore, among the biomarkers in each area, only inflammation was significantly associated with life expectancy in all age groups of 85–99 years old, 100–104 years old, and 105 years old and over. In any age group, it was found that the group with low inflammatory indices had higher ADL cognitive function than the group with high inflammatory indices. Furthermore, we found that inflammatory markers were also low in centenarians’ offspring. It is only recently that studies with mice have proved that inflammation is a factor that accelerates aging, but here, we were able to prove the relevance in the aging process of humans.
Based on this finding, if a drug that suppresses inflammation with aging could be developed safely, there is a possibility that the quality of life of elderly people could be greatly improved.
Arai Y, Martin-Ruiz CM, Takayama M, Abe Y, Takebayashi T, Koyasu S, Suematsu M, Hirose N, von Zglinicki T. Inflammation, but not telomere length predicts successful ageing at extreme old age: a longitudinal study of semisupercentenarians. EBioMedicine 2015;;2(10):1549-58. doi: 10.1016/j.ebiom.2015.07.029.
3. TULIP consortium
( Towards Understanding Longitudinal International older People Studies)
With population aging worldwide, the increase in disability rate and long-term care usage is considered one of the most serious issues facing the international community in the 21st century. In 2014, researchers from Leiden University in the Netherlands, the University of Newcastle in the UK, the University of Auckland in New Zealand, and our Keio University gathered and established the Towards Understanding Longitudinal International Older People Studies (TULIP) consortium as a collaboration of four cohort studies of the very old (85 years or older). The consortium aims to clarify the universal mechanisms of aging by comparing the health status of very old people in countries with vastly different lifestyles, cultural backgrounds, and life expectancy, as well as the importance of factors in maintaining independent living and quality of life. In June 2019, the TULIP consortium’s international conference was held at Keio University’s Shinanomachi campus, where researchers from four countries had a heated discussion and friendship.
(1) Palapar L, Kerse N, Rolleston A, den Elzen WPJ, Gussekloo J, Blom JW, Robinson L, Martin-Ruiz C, Duncan R, Arai Y, Takayama M, Teh R; TULIP Consortium. Anaemia and physical and mental health in the very old: An individual participant data meta-analysis of four longitudinal studies of ageing. Age Ageing. 2020 Sep 16:afaa178.
(PMID: 32939533; DOI: 10.1093/ageing/afaa178)
(2) Du Puy RS, Poortvliet RKE, Mooijaart SP, den Elzen WPJ, Jagger C, Pearce SHS, Arai Y, Hirose N, Teh R, Menzies O, Rolleston A, Kerse N, Gussekloo J. Outcomes of Thyroid Dysfunction in People Aged Eighty Years and Older: An Individual Patient Data Meta-Analysis of Four Prospective Studies (Towards Understanding Longitudinal International Older People Studies Consortium). Thyroid. 2020 Nov 2. (PMID: 33012278; DOI: 10.1089/thy.2020.0567)
4. Collaboration between the Singapore 90 study and the Kawasaki Aging and Wellbeing Project
The population is aging rapidly, especially in the Asian region, and the future burden of medical and long-term care is becoming a serious concern. Like Japan, Singapore has a high rate of elderly population and a declining birth rate, and the Singapore 90 Study (SG90) is being conducted to identify the factors that are important for improving the health of the elderly and to develop effective preventive programs. Just as SG90 was being launched, Keio University, in collaboration with Kawasaki City, organized the Kawasaki Aging and Wellbeing Project (KAWP), which brought together researchers from both universities who had already had a close relationship with each other and proposed a cohort collaboration aimed at addressing future aging in Asia. From the planning stage, the researchers from the National University of Singapore and Keio University have worked together to develop a research plan that include common health assessment of the elderly as much as possible. The project is supported by the Agency for Science, Technology and Research of Singapore (A*STAR) and the Japan Agency for Medical Research and Development (AMED).