What if told you that your lifespan is probably predictable from a biopsy?

Today I have the pleasure to discuss state-of-the-art epigenetic clocks for biological age and lifespan estimation to develop interventions that slow down aging with my former mentor Professor Alessandro Cellerino. Prof Cellerino is a world leader in aging and longevity research. He is an Associate Professor and Research group leader at the Scuola Normale Superiore in Pisa and the Leibniz Institute on Aging.

Prof Cellerino and I discuss how he and his collaborators established quickly and with great success Nothobranchius furzeri, Killifish for friends, as a model organism for aging research, so to test pharmacological and non-pharmacological interventions with the hope to slow down or reverse the aging process. But this needs to measure aging and how fast it proceeds for different individuals, leading us to discuss epigenetic clocks, which might effectively predict your biological age from a simple biopsy from your skin! So if you happen to have a biological age which is more than your chronological age, take action, it means you are aging faster than your same-year old high-school peers! We discuss how striking the RNA-seq revolution has been also for the aging field, how conditions that result in faster or slower aging are probably often set early, much before the aging process begins. We analyze some of the common machine learning techniques employed by epigenetic clocks, and the difficulties to infer causality and identify crucial genes, as several different combinations of relatively few genes can all equally well predict biological age. Finally, we reason on the importance of multi-species clocks for translational research: clocks that work both in model organisms and in humans, such as the transcriptiomic clock just published by Ferrari et al. in the Cellerino Lab, which employs an innovative architecture to control for the effect of confounders such as sex on the age prediction. Looking forward to seeing what Prof Cellerino and the Cellerino lab achieve in the next few years!

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RESOURCES

[ACADEMIC – a great paper illustrating the role of the Nothobranchius furzeri “Killifish” in aging research] Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan: https://www.cell.com/fulltext/S2405-4712(16)30030-8

[ACADEMIC] A deep neural network provides an ultraprecise multi-tissue transcriptomic clock for the short-lived fish Nothobranchius furzeri and identifies predicitive genes translatable to human aging: https://www.biorxiv.org/content/10.1101/2022.11.26.517610v1

[ACADEMIC, foundational review on epigenetic clocks] DNA methylation-based biomarkers and the epigenetic clock theory of ageing: https://www.nature.com/articles/s41576-018-0004-3

The Cellerino Lab: https://www.leibniz-fli.de/research/associated-research-groups/cellerino/current-projects-and-team