Donald Craig Willcox

Okinawa International University, Japan

Title: Islands of Longevity: Genetic & Lifestyle Insights from Okinawa & Hawai‘i

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Biography

Donald Craig Willcox, PhD, MHSc, FGSA, has dedicated over two decades to researching the genetic and lifestyle factors that contribute to healthy aging and longevity. He currently serves as Co-Principal Investigator of the Okinawa Centenarian Study and Head of the Okinawa Research Center for Longevity Science R&D. He is also a co-investigator and consultant for multiple NIH-funded studies, including the Kuakini Hawaii LIFESPAN and HEALTHSPAN Studies, which are part of the long-running Kuakini Honolulu Heart Program.

He is Fluent in Japanese and brings extensive expertise in bio-cultural approaches to aging, with a multidisciplinary background spanning anthropology, epidemiology, nutrition, and human genetics. He has successfully led cross-national research collaborations supported by the National Institute on Aging, the Japan Society for the Promotion of Science, and other major funding agencies.

His Okinawa team was the first to identify human longevity-associated gene variants (Lancet, 1987), and his Hawaii team discovered that the FOXO3 gene significantly influences human lifespan (PNAS, 2008). With over 40 years of collective experience in geriatrics and gerontology in Okinawa and more than 50 years of genetic epidemiology research in Hawaii, he continues to be a leading voice in the science of aging.

Abstract

Okinawa and Hawai‘i—two Pacific islands connected by a long history of migration and cultural exchange—have also emerged as scientific partners in the study of exceptional longevity. Okinawa is internationally recognized as the first identified Blue Zone, a region characterized by high numbers of centenarians and low prevalence of age-related diseases. In Hawai‘i, the Kuakini Honolulu Heart Program (HHP) has followed a cohort of Japanese-American men for over 50 years, producing one of the world’s most comprehensive datasets on aging. Together, these “islands of longevity” offer a rare opportunity to examine aging through the lens of both lifestyle and genetics. A central focus of this research is the FOXO3 gene, one of the most robustly validated human longevity genes. FOXO3 plays a key role in cellular stress response, inflammation regulation, and mitochondrial health. A specific FOXO3 variant has been associated with reduced telomere shortening, increased resilience to cardiometabolic disease, and extended lifespan. The Okinawan population’s exceptional healthspan is shaped not only by genetics but also by lifestyle factors, particularly diet. The traditional Okinawan diet is low in calories yet dense in nutrients and antioxidants, emphasizing vegetables, legumes, and marine-based foods. A culturally ingrained practice known as hara hachi bu—which encourages eating until only 80% full—functions as a natural form of caloric restriction, a dietary pattern shown to reduce oxidative stress, suppress inflammaging, and enhance metabolic efficiency. Our recent findings also highlight the potential of astaxanthin, a marine-derived antioxidant found in microalgae and seafood, as a dietary activator of FOXO3. Experimental data suggest that astaxanthin promotes FOXO3 expression and nuclear translocation, offering a promising nutrigenomic approach to modulate aging pathways. This presentation will summarize key discoveries from ongoing Okinawa–Hawai‘i collaborations and preview future directions focused on mitochondrial function, inflammaging, and integrative strategies to promote healthy lifespan across diverse populations.