Last month, I attended Wellcome Connecting Science’s virtual conference on Healthy Ageing. The conference was designed to bring researchers together from across the wide-ranging field of ageing in order to promote communication across disciplines, from cell biology to epidemiology.
Several talks focused on the senescence-associated secretory phenotype (SASP), by which many senescent cells exert harmful effects on neighboring cells via the secretion of inflammatory cytokines, immune modulators, growth factors, and proteases. Both Peter de Keizer (University Medical Center Utrecht) and Darren J. Baker (Mayo Clinic) showed how the selective removal of these cells can slow ageing or disease progression in mouse models of defective DNA damage repair and Alzheimer’s disease, respectively.
Judith Campisi (Buck Institute), in her excellent keynote address, expanded on two classes of drugs currently being developed to combat SASP-driven ageing: senolytics, which selectively eliminate senescent cells, and senomorphics, which suppress certain SASP pathways. As senescent cells can also play important roles in tissue development and repair, a major challenge is to target only those senescent cells that are deleterious rather than beneficial.
Aside from SASP, other mechanisms of ageing explored by the speakers included cellular drivers of protein aggregation (Ellen Nollen, University of Groningen); ribosome pausing during translation (Judith Frydman, Stanford University); age-acquired X chromosome inactivation (Amy Roberts from Kerrin Small’s lab, King’s College London); and impaired meningeal lymphatics (Jonathan Kipnis, Washington University). Conversely, several talks focused on anti-ageing mechanisms and potential therapeutic approaches, including activation of the unfolded protein response during cellular stress (Rebecca Taylor, Medical Research Council Laboratory of Molecular Biology); mitochondrially-targeted dosing of hydrogen sulfide to extend healthspan and lifespan in C. elegans (Adriana Vintila from Timothy Etheridge’s lab, University of Exeter); ectopic activation of meiotic rejuvenation pathways to extend lifespan in mitotically-dividing yeast (Elçin Ünal, University of California, Berkeley); and personalized nutrition in older adults (José Ordovas, USDA).
As an evolutionary biologist by training, I was particularly interested in a pair of talks focusing on the ageing process across species. Alex Cagan (Inigo Martincorena’s lab, Wellcome Sanger Institute) and colleagues used whole genome sequencing to measure somatic mutation rates in 16 species of mammals. While lifespan varied 30-fold across these species, the end-of-lifespan mutational burden varied only threefold, pointing to differences in mutation rates that may help explain the paradoxical lack of a cross-species correlation between lifespan and cancer incidence. Mirre Simons (University of Sheffield) also took a comparative approach, investigating differential gene expression caused by dietary restriction in eight species of Drosophila. Most of the genes involved in the dietary restriction longevity response were specific to Diptera, a surprising result as this response is thought to be evolutionarily conserved.
Also in the cross-species department, Lena Pernas (University of Cologne) gave a fascinating and somewhat unsettling talk on the microbial co-opting of cellular senescence. Her lab found that the human parasite Toxoplasma gondii, which infects an estimated third of the population, induces cellular senescence in both infected cells and non-infected neighboring cells. In turn, these senescent cells promote the development of the chronic stage over the acute stage of the parasite, producing latent reservoirs that enable chronic infection and prolonged host-to-host transmission.
For those interested, more information on the meeting can be found at: https://coursesandconferences.wellcomeconnectingscience.org/event/healthy-ageing-virtual-conference-20220525/