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As populations grow older, societies face mounting social, economic, and health challenges, making it increasingly urgent to find interventions to slow the effects of ageing.
The proportion of Singapore residents aged 65 and above grew from 7.2% in 2000 to 16% in 2021 and is projected to reach 24.1% by 2030. This demographic shift highlights the need for significant infrastructural and personal care resources. Longer life expectancy also brings with it a need to prevent physical decline and frailty in older adults.
One way scientists from Duke-NUS' Centre for Ageing Research and Education are tackling this is by developing novel AI screening tools to identify senior citizens most at risk of falling and reducing that risk through tailored, multi-modal and multi-component interventions, work that is underway in a randomised clinical trial.
Scientists at Singapore’s only graduate-entry medical school are also harnessing regenerative medicine to improve the quality of life of ageing populations. By developing therapies that target the root causes of ageing, such as muscle degeneration and impaired tissue repair, they hope to extend not just lifespan but also healthspan — the period during which people remain active and independent. These interventions could yield vast social and economic benefits, reducing the burden on healthcare systems while enhancing the lives of the elderly.
"Here at Duke-NUS, we aren’t just focused on extending life. We want our research to enhance how individuals and communities experience their later years. From combatting a fear of falling and the chronic inflammation we accumulate with age to restoring mobility, cognition and metabolism, our innovations lead to practical health solutions. These efforts empower older adults, and others worldwide, to lead fuller, more vibrant lives for longer." - Patrick Tan, Senior Vice-Dean for Research at Duke-NUS
Is a protein the hidden enemy of youth?
In earlier work, researchers from Duke-NUS had linked the protein interleukin-11 (IL11) with inflammation in the heart, kidneys, liver, and lungs. Then, they discovered that IL11 levels rise with age, promoting inflammation and accelerating ageing.
Two mice, both the same age. The one on the left has aged normally, but the one on the right has been given an anti-ageing drug.
In experiments on mice, the researchers either genetically prevented the production of IL11 or treated the mice with a drug that removed the protein. These interventions extended the mice’s healthspan (the number of years lived in good health) and lifespan (time lived) by up to 25%, in both sexes.
The researchers nicknamed the treated mice “supermodel grannies ” because they appeared younger, were healthier, and developed fewer cancers than untreated mice. They also demonstrated improved metabolism and muscle function, had healthier fur, and got lower scores on frailty tests.
Anissa Widjaja looks at a western blot, a technique used to identify specific proteins.
With this data, which was published in Nature, the researchers plan to advance the drug into human trials to see whether it would have the same anti-ageing effect without causing side effects. “Although our work was done in mice, we hope that these findings will be highly relevant to human health,” says the study’s lead author, Anissa Widjaja of Duke-NUS’ Cardiovascular and Metabolic Disorders Programme.
Growing neurons to fight degeneration
The brain is the most intricate organ in the human body and a vital part of who we are. But with age, brain cells lose the regenerative abilities to help them recover when they’re damaged by ageing or disease. A new method developed by scientists at the GK Goh Centre for Neuroscience at Duke-NUS, which was established through a S$5 million gift from the GK Goh family, makes it possible to grow specific neurons from stem cells in the lab, offering new hope for treating conditions like Alzheimer’s, Parkinson’s, and stroke.
The team has successfully grown norepinephrine neurons — specialised cells that control functions like memory and movement. These neurons are particularly vulnerable to degeneration in diseases such as Alzheimer’s and Parkinson’s, often deteriorating long before symptoms appear.
Regenerated neurons viewed under microscope.
“With these functional brain cells, we can study how they age and uncover their roles in neurodegenerative conditions. The insights we gain will help find new and more effective therapies to treat brain diseases and perhaps even slow the ageing process,” explains Zhang Suchun, director of the centre and one of the study’s authors.
In addition, the researchers used such stem-cell-derived neurons to repair brain tissue in stroke patients. They transplanted neurons into damaged areas using a chemical mixture which protected the cells from inflammation in the stroke-affected brain. Over 30 days, the transplanted neurons survived, matured, and restored damaged tissue.
The method, published in Advanced Science, has since been licensed, and the team plans to start preclinical safety studies using the same approach in Parkinson’s disease.
Bats’ immune mysteries: Nature’s blueprint for resilience
Bats are remarkable among mammals for their long lifespan and resilience against age-related diseases. Their unique immune system allows them to coexist with viruses without falling ill, a trait that intrigued scientists at Duke-NUS’ Emerging Infectious Diseases Programme.
The researchers, led by Wang Linfa, discovered that bats control inflammation through a protein called ASC2. This protein dampens the activity of inflammasomes, key immune system components that can trigger harmful inflammation during viral infections in humans.
Drip feeding an Eonycteris spelaea, or cave nectar bat, a special food mixture that replicates their natural diet.
“This suggests that the high activity of ASC2 is a key mechanism by which bats keep inflammation under control, with implications for their long lifespan and unique status as a reservoir for viruses,” explains Matae Ahn, a Duke-NUS MD-PhD graduate, senior research fellow and first author of the study published in Cell.
Wang, senior author of the study says, “Whether we’re talking about Ebola or a coronavirus, it’s not the virus that kills us. It is the inflammation triggered by the virus that can be lethal.”
Unlike humans, bats keep inflammation in check. When scientists compared the bat ASC2 protein to the human version, they found four key differences that make the bat protein more effective at limiting inflammation.
Matae Ahn (right) investigated the similarities between the human and bat immune responses in the search of new treatments.
Paratus Sciences, a biotech startup based in New York and Singapore focused on unlocking novel disease targets and accelerating drug discovery by leveraging the extraordinary adaptive biology of bats, has in-licensed the IP underlying the ASC2 work, and is translating these discoveries into a new class of anti-inflammatory drugs. Paratus Sciences is also collaborating with Wang’s group on a broader investigation of bat immunology and viral tolerance for new insights with therapeutic potential.
Muscle health matters
Sarcopenia, a condition causing the gradual loss of muscle mass and strength, is a growing public health concern affecting millions of older adults. Researchers at Duke-NUS have made a promising discovery that could improve treatments for this debilitating condition.
Their study, published in Autophagy, shows that maintaining optimal levels of the protein DEAF1 (Deformed Epidermal Autoregulatory Factor-1) is essential for effective muscle repair and regeneration. DEAF1 plays a key role in regulating autophagy, the process by which cells remove and recycle damaged components.
Tang Hong-Wen (standing) and his team discovered that DEAF1 plays a key role in sarcopenia and cancer-related muscle wasting.
As we age, muscle stem cells become less effective at repairing and regenerating muscle tissue, contributing to muscle loss in sarcopenia. The study found that DEAF1, controlled by proteins known as FOXOs, helps muscle stem cells maintain balanced autophagy levels. This allows the muscle stem cells to stay healthy and perform their critical role in muscle repair. However, FOXO activity decreases with age, leading to an imbalance in DEAF1 and impaired muscle repair, notes Tang Hong-Wen, senior author of the study.
FOXO activators have demonstrated promise in restoring DEAF1 equilibrium, boosting muscle stem cell activity, and promoting muscle regeneration in preclinical trials. These findings could pave the way for new medicines to treat sarcopenia and other muscle-degenerative disorders by enhancing muscle repair processes and improving overall muscle health.