FEBS Junior Section present Jan Hoeijmakers

Update! Watch the recording of this talk.
This talk is an activity from the FEBS Junior Section, an initiative set up by students and young researchers from some of the FEBS Constituent Societies. Each month members of the FEBS Junior Section organize an online event on either a research or a career topic. This talk was coordinated by the Young-NVBMB, the Junior Section of the Netherlands Society for Biochemistry and Molecular Biology (NVBMB).
Speaker: Prof. Jan H.J. Hoeijmakers
Affiliations: Dept. of Molecular Genetics, Erasmus Medical Centre (Rotterdam, The Netherlands); the Princess Máxima Center for Pediatric Oncology (Utrecht, The Netherlands); Oncode Institute (Utrecht, The Netherlands); and CECAD, University of Cologne (Cologne, Germany)
Topic: “DNA damage repair and the impact of nutrition on the process of aging and opportunities to promote healthy aging”
Time: 23 January 2025, 19:00 (CET)
For more information: See the abstract and biosketch below.
Biosketch
Jan Hoeijmakers heads research teams at the Erasmus Medical Center (Rotterdam), the Princess Máxima Center for Pediatric Oncology (Utrecht), the Oncode Institute (Utrecht) and at the CECAD, Univ. of Cologne (Cologne). He made major contributions to the field of DNA damage and repair, discovering that accumulating DNA damage causes systemic aging and that dietary restriction delays aging by reducing DNA damage, with clinical implications for dementia, chemotherapy, surgery and organ transplantation, impacting major areas in medicine. He received many (inter)national prizes and distinctions.
Abstract
Aging appears remarkably plastic: e.g., suppressing insulin signalling extends lifespan in numerous species. However, virtually all premature aging syndromes link with genome instability. We have generated mouse models which strikingly mimic human DNA-repair-deficiency syndromes and display wide-spread accelerated aging, and a lifespan of a few months. Simultaneously, they exhibit an anti-aging ‘survival response’, which suppresses growth and enhances maintenance, resembling the longevity response induced by dietary restriction (DR) as an attempt to delay the accelerated aging.
Interestingly, subjecting these progeroid mutants to actual (30%) DR tripled their lifespan, and drastically retarded accelerated aging, most notably neurodegeneration preserving 50% more neurons and maintaining full motoric function. The DR response in these mice resembled DR in wild type animals including reduced insulin signaling and reduced DNA damage load, explaining how DR delays aging and why DNA repair mutants overrespond. Interestingly, gene expression profiles of somatic organs showed gradual decline of expression preferentially of long genes, consistent with genome-wide accumulation of stochastic, transcription-blocking lesions, which affect long genes more than short ones. This phenomenon was also discovered in normal aging of post-mitotic tissues. DR largely prevented transcription stress, indicating that DR prolongs genome function. We will present phenotypes of conditional DNA repair models targeting aging to selected organs, striking parallels with Alzheimer’s disease and the first remarkable results translating these concepts from mice to progeroid children. Our findings identify DNA damage as main cause of aging, establish repair-deficient mice as powerful models for interventions to promote healthy aging, reveal untapped potential for reducing endogenous damage and transcription stress in neurodegeneration, explain the molecular anti-aging mechanism of DR and the aging component of proteinopathies based on transcription stress and promote a counterintuitive DR-like interventions for progeroid syndromes, preventing neurodegenerative diseases and ischemia reperfusion damage in surgery and for improving chemotherapy outcome.
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