Living a hundred years healthy: what works and what doesn’t according to science

In Kyotango, Kyoto Prefecture, the rate of centenarians is three times the Japanese national average. There people live longer and, it seems, even better: strong social ties, a diet rich in vegetables, daily physical activity. It was held right here the first World Longevity Summit to understand how to extend not only the duration, but above all the quality of life. But what are, on a scientific level, the factors that promote longevity? A report just published on Nature summarizes the summit sessions, from molecular biology to community strategies, with a common goal: reducing the gap between life expectancy and years lived in good health.

Epigenetic clocks

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Steve Horvath of Altos Labs presented epigenetic clocks, mathematical models based on DNA methylation that estimate biological age, which can be very different from chronological age. These clocks detect prenatal development and show complete rejuvenation when cells are reprogrammed into induced pluripotent stem cells. Children of centenarians have younger epigenetic ages, underscoring genetic and lifestyle influences on longevity. Aging varies between organs: in centenarians, the cerebellum and retina age more slowly, while blood and bones accelerate.

In Kyoto, Horvath presented GrimAge, a biological clock that incorporates protein biomarkers and smoking history to predict mortality and disease risk. “Obesity accelerates liver aging, while exercise and dietary changes lead to minimal reductions in biological age,” he said. A Swiss clinical study found that omega-3 supplementation led to a small but significant reduction in biological age, while vitamin D and exercise showed no significant impacts. He then presented a universal clock for mammals that estimates relative biological age in over 180 species, allowing direct comparisons between species. With this instrument the scientist – as he had anticipated a Journal a few months ago – showed that interventions such as calorie restriction, growth hormone deficiency and hibernation are associated with slower biological aging, while high-fat diets and genetic conditions such as Down syndrome accelerate it.

Autophagy

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Tamotsu Yoshimori of Osaka University explained autophagy, a process in which damaged organelles and proteins are encased in autophagosomes and degraded by lysosomes. Although autophagy was first described in the 1950s, its molecular mechanisms remained obscure until Yoshinori Ohsumi’s discovery of ATG genes in yeast, which transformed the field and earned her a Nobel. His team identified Rubicon, a protein that inhibits autophagy. “Rubicon expression increases with age, impairing autophagic function. Reducing Rubicon, especially in neurons, extended lifespan and improved motor function,” he explained. Rubicon also promotes the release of exosomes carrying senescence-inducing microRNAs, suggesting that Rubicon promotes aging not only by impairing autophagy but also by facilitating the intercellular spread of senescence signals.

Microbiome

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Francis Chan of the Chinese University of Hong Kong, however, emphasized the gut microbiome as a central regulator of healthy aging. He described how the microbiome develops from birth, initially shaped by maternal transmission and subsequently by diet and environment. With age, intestinal function declines, microbial composition changes, and inflammation increases. These changes contribute to immunosenescence, cognitive decline, metabolic disorders, and increased vulnerability to infections.

Centenarians do not maintain a youthful microbiome. Instead, they show a reduction in core microbial species and increased diversity, suggesting a unique microbial adaptation associated with advanced age. In healthy intestinal aging, a decline in mucus-degrading bacteria such as Bacteroides it is counterbalanced by beneficial species such as Akkermansia And Bifidobacteriawhich help preserve the integrity of the mucosa. In Kyoto, Chan discussed three key microbial metabolites: butyrate, exopolysaccharides and spermidine. These compounds can promote longevity by modulating epigenetics, mitochondrial function, and autophagy. Finally, it introduced a longitudinal birth cohort study in Hong Kong and mainland China. The findings revealed, for example, that infants born during the COVID-19 pandemic showed delayed microbial maturation and increased risk of allergies, likely due to increased use of disinfectants.

Platinum Society

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Tomoo Matsuda from the Mitsubishi Research Institute presented the concept at the symposium Platinum Societywhich reimagines older adults as active contributors to society. It showed that Community initiatives that promote social participation, daily activity and intergenerational connections may contribute to a decline in long-term care needseven amidst an aging population. He introduced Exadon as a representative example of community programs: combines exercise, traditional Japanese taiko drumming, and group interaction, designed to promote physical well-being and social connection among older adults. He also highlighted community practices such as multi-purpose centers where elders mentor children, illustrating how intergenerational engagement can benefit society.

Italian research

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Last but not least, Stefania Bandini of the University of Milan-Bicocca explained how digital tools and geographical data can support elderly populations, especially in rural regions. The discovery passes through AGE-IT, a large national research initiative in Italy that addresses the social and technological challenges of an aging society.

Bandini illustrated the challenges facing Italy’s “internal areas”, which comprise 60% of the national territory and are home to 22% of the population. These regions, much like rural Japan, struggle with depopulation, limited infrastructure, and reliance on informal care networks. “While traditional diets, strong social ties and clean environments in these areas support healthy ageing, the outward migration of younger generations has led to social fragmentation, loss of traditional knowledge and decline in access to essential services,” he explained. To design infrastructure that meets the needs of older populations in rural areas, Bandini says walkability is an essential factor, especially in mountainous terrain. Through case studies, he explained how Geographic Information Systems, artificial intelligence and IoT technologies can help identify local vulnerabilities, such as limited access to medical care, nutritious food and support servicesand support the planning of targeted interventions.

All findings that highlight the importance of integrating digital innovation with local needs and conditions to promote age-friendly environments in rural communities. The summit closed with a statement identifying four pillars: social connections and communication, meals rich in plant-based protein and fiber shared with others, daily routines with physical activity, and living with gratitude and Ikigai, the sense of purpose. Things that seem to happen spontaneously in Kyotango and that science is now trying to understand.