Vortrag von Ph.D. Oliver Hahn2. April, 2023 2023-04-02 1:01
Am Mittwoch, 18. Dezember 2019, wird Ph.D. Oliver Hahn (Wyss-Coray lab, Neurology and Neurological Sciences, University of Stanford, School of Medicine, Stanford California) einen Vortrag im Rahmen der ZBI “Distinguished Speaker Series” zum Thema “Tracing the origin of organismal ageing in health and disease through integrative systems biology” halten.
Ageing is the leading risk factor for chronic disease and disability, posing rising threat for healthcare systems and social property around the globe. Changes in gene expression can be a readout of the progressing cellular deterioration and inter-tissue dynamics accompanying the ageing process, thereby granting insights into the origin and onset of organismal frailty. Leveraging the advents of multi-layered ‘omics’ datasets, we longitudinally profiled mice throughout their entire lifespan and across all major tissues. We use these rich datasets to characterize the tissue-specific ‘ticking rate’s of ageing and aim to uncover how organs in health and disease may communicate through cellular trafficking and secretion of protein factors. By developing novel algorithms to integrate single-cell transcriptomes and bulk RNA-seq time course data, we identify the direct cellular origin of age-related expression changes, including an accumulation of T- and B-cells in white adipose tissues (WAT) of middle-aged mice. These involve plasma B-cells with a pronounced antibody-secreting phenotype, which become consecutively present in other tissues like heart and kidney.
We investigate in parallel the possible, systemic consequences of aged, inflamed WAT by characterizing the response to dietary restriction (DR), a nutritional intervention known to improve health- and lifespan. Concomitantly, we discover that WAT from old mice exhibits a largely refractory transcriptional and metabolic response to DR, indicating a nutritional memory effect. We combine these analyses with large-scale lifespan studies of over 800 mice and show how DR in aged animals can no longer improve survival.
Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of ageing – with the WAT playing a key role – thus providing a foundation to track systemic sources of declining health at old age.