Abstract
Over the past year, Cell Stem Cell has introduced early-career researchers impacted by the COVID-19 pandemic and subsequent closures to our readers. One year since our first introductions, we’ve invited several participants to reflect on their experiences and key issues. In this Story, Weiqi Zhang discusses her lab’s research focus and how they found opportunities during COVID-19 shutdowns to provide new resources for the aging research community.
Over the past year, Cell Stem Cell has introduced early-career researchers impacted by the COVID-19 pandemic and subsequent closures to our readers. One year since our first introductions, we’ve invited several participants to reflect on their experiences and key issues. In this Story, Weiqi Zhang discusses her lab’s research focus and how they found opportunities during COVID-19 shutdowns to provide new resources for the aging research community.
Main text
Aging is a process that we all face, and its biology has long fascinated me. The mechanism of aging remains elusive, and my curiosity about this enigma drives my lab’s daily research. Stem cell aging is critically linked to organismal aging. To address the fact that primate aging usually takes years, we established an accelerated aging model using human stem cells and linked stem cell homeostasis to compact heterochromatin. Recently, using CRISPR-based screening, we identified histone acetyltransferase KAT7 as a new aging-linked gene, inhibition of which reshapes chromatin structure and delays cell senescence. More importantly, we showed that CRISPR-Cas9-mediated Kat7 knockout alleviated liver senescence and extended healthspan and lifespan of mice, demonstrating the therapeutic potential of KAT7 inactivation in aging-related processes. This link between epigenetic factors and rewiring the molecular program of aging gives me hope that we can one day understand this process. My lab seeks to integrate the advantages of different disciplines such as multi-omics, bioinformatics, chemical biology, and genetic engineering to provide new ideas for the treatment of aging-related diseases. During the COVID-19 pandemic, we still adhered to our research direction by adapting our research approaches and thinking differently about how we investigate the molecular underpinnings of aging.
I think of aging as studying a community. The individuals (cells) are prone to aging, and intrinsic changes (in organelles, epigenetics, and molecular pathways, etc.), can change communication between individuals (cell-cell interaction). The community environment (chronic inflammation, nutritional supply, etc.) has a deep impact, too. By studying this “community ecosystem,” we hope to identify early biomarkers and intervention targets to mitigate the effects of, and even delay, aging. We are also exploring new methods to delay cellular senescence or expand the lifespan/healthspan of animal models.
During the outbreak of the pandemic last year, we could not routinely go to the laboratory, and then we began to think about what could be done to make the best use of our time
In doing so, we realized that aging research is inseparable from bioinformatics and data science. High-throughput omics technologies (including genomics, transcriptomics, epigenomics, proteomics, metabolomics, and metagenomics) have been widely applied in aging studies, facilitating large-scale profiling of aging-associated molecular changes and regulatory states. In addition, emerging methods are allowing us to probe aging at single-cell resolution, providing integrated and multi-dimensional data at an unprecedented scale and depth. As a result, a growing volume of valuable aging-related data necessitates an open, integrated database to support new lines of aging research. During the outbreak of the pandemic last year, we could not routinely go to the laboratory, and then we began to think about what could be done to make the best use of our time. We soon realized that accelerating the construction of an aging-related database might be an excellent idea. We therefore established the Aging Atlas (https://bigd.big.ac.cn/aging/index) to collect multi-omics data related to aging, providing a broad map of the community of tissues we study for researchers. The Aging Atlas provides user-friendly functionalities to explore aging-related changes in gene expression and provides download services for raw multi-omics data from aging-related researches. The database is currently online, and more than 25 countries have accessed the database in a short period of time. As a continuation of this work, we are also constructing a sister database, called the Regeneration Roadmap, or RR for short, to include multi-level omics data related to regeneration.
In 2020, we also spent much time analyzing the sequencing data we had already obtained and consulting a large amount of literature to help us interpret these data. At the same time, we tried our best to keep the laboratory operational as long as possible. In addition, we had more time to read papers, write, and publish reviews. Last year, we reviewed the epigenome of aging and conducted systematic discussions on epigenetic changes that occur during aging, and on how life-extending interventions modulate epigenetic factors to alleviate aging features. In fact, due to the reduction of meetings, business trips, and social time, we were able to concentrate more on scientific research. This includes having more time to communicate with colleagues and students and thinking more deeply about the implications of our research.
Thanks to the efforts of the Chinese government, our life and work have basically returned to normal this year. However, some of our pandemic habits have remained, such as online group meetings and regular cloud salons. Caring more about your friends and partners and exercising more are also important lessons from the epidemic. I am fortunate to have excellent collaborators, a community of researchers that together explores the mysteries of aging in synergy.