Wilbert P. Vermeij

Dr. Ing. Wilbert Vermeij is an expert in the field of DNA damage and accelerated aging. During his PhD at the Leiden University, he initially identified novel functions of skin cornification proteins throughout the body under stress conditions, boosting protective anti-oxidant capacities and accelerating tissue regeneration after injury. Subsequently, as Scientist at DNage B.V., he was involved in the identification of biomarkers/targets for various age-related diseases. In 2011, this research was continued in the Molecular Genetics department of the Erasmus MC Rotterdam, which is one of the world’s leading DNA repair research groups.

Using mouse mutants closely mimicking rare human DNA repair deficiency syndromes, we disclosed a causal link between DNA damage and aging, and hypothesized accelerated aging in children and adults treated with DNA-damaging chemotherapeutics during cancer treatment. He represented the department, in one of the largest EU-consortia MarkAge, for the identification of human biomarkers that could serve as a measure of biological age. Additionally, he was co-founder of AgenD, a spin-off company whose mission was to provide solutions for medical/health problems associated with aging.

He discovered that dietary restriction (DR) drastically retards numerous aspects of accelerated aging (Nature 2016): animals retained 50% more neurons, attenuated DNA damage levels, and tripled lifespan of progeroid mice for which he received the prestigious ADPS Longevity Research Award. Even when specifically targeting a DNA repair defect to one neuronal subtype, causing local accelerated aging and neurodegeneration, DR lowers the damage load and retains neuronal functioning. At the same time, we found that, since DNA damage occurs stochastically, longer genes were more hampered and declined in transcriptional output compared to shorter genes (Nature 2016). This phenomenon of transcription stress we first discovered in accelerated aging DNA repair-deficient mice and normal human brain aging, which was later confirmed by others conserved in many organs and species. DR diminished this DNA-damage-induced transcriptional stress by lowering DNA damage levels and revealing one mechanism by which DR delays aging, which was still mysterious since its discovery about 90 years.

Surprisingly, the protective response by DR even works in preventing and reducing neurodegeneration in animals where the DNA repair-defect is specifically targeted to one neuronal cell-type, indicating that DR influences damage build-up in a cell intrinsic manner, even in the brain where transcriptional changes by DR are limited due to the blood-brain-barrier, and thus might also trigger benefits in disease settings in which a part of the body or brain is aged in an accelerated fashion, but the rest still considered healthy (Front Aging Neurosci 2023). Remarkably, the benefits of DR could be further enhanced by combining with an intervention boosting muscle growth, yielding extended lifespan, improved health and reduced damage, even when applied late in life, opening opportunities for translation to human (J Cachexia Sarcopenia Muscle 2024). Together with clinicians, researchers and patient organizations, he now translates these findings towards children with genetic DNA repair deficiency syndromes.

Since 2017, at the Princess Máxima Center and Oncode Institute, he fundamentally unravels how DNA damage from endogenous and exogenous sources causes transtription stress and contributes to natural and accelerated aging (Cancers 2022; Best Paper Award). Additionally, he studies the effect of nutritional preconditioning as effective intervention for sustaining health and preventing surgery related ischemia-reperfusion injury and chemo- and radiotherapy-induced toxicities and late-life effects for pediatric oncology patients (e.g., FIURTT-Study Máxima), covering the entire range from cultured cells, organoids, organotypic tissue slices and mouse models to recent clinical trials in patients.

LinkedIn: https://www.linkedin.com/in/wilbert-vermeij-93b6a928/
ORCID: https://orcid.org/0000-0002-9690-1385