In:
Science, American Association for the Advancement of Science (AAAS), Vol. 380, No. 6650 ( 2023-06-16)
Abstract:
Aging is a natural process that is associated with the gradual decline of tissues in the body. This process increases the risk of developing various diseases, such as cardiovascular and neurodegenerative diseases and cancers. The study of aging has a long history, and several aging hypotheses have been proposed. Nonetheless, there are still many unanswered questions when it comes to understanding the effects of aging on the composition and maintenance of different cell types. It is also not clear whether all cell types age at the same rate or whether the transcriptome of one cell type can be used to predict age. Additionally, the genes and signaling pathways that contribute to aging in different cell types are not yet fully understood. RATIONALE Drosophila melanogaster , commonly known as the fruit fly, has played a vital role in advancing the fields of genetics, neurobiology, development, and aging. A large portion (~75%) of genes associated with human diseases have counterparts with functional similarity in the fly. The fly is also a useful model organism for studying the aging process, as it displays several age-related functional changes observed in humans, such as decreased motor activity, learning and memory, cardiac function, and fertility. Therefore, a comprehensive understanding of the molecular and genetic mechanisms underlying age-related decline in flies can provide valuable insights not only for aging studies in this species but also in other organisms, including humans. RESULTS Advancements in single-cell RNA sequencing technologies and the creation of the Fly Cell Atlas (FCA) have enabled the investigation of aging phenotypes at the single-cell level in D. melanogaster . Here, we present the Aging Fly Cell Atlas (AFCA), a single-nucleus transcriptomic map that characterizes changes in most tissues of male and female flies across their life span. Our analysis provides insights into age-related gene expression changes, alterations in cell composition, and common pathways that correlate with aging. Notably, we observed an increase in fat body nuclei and elevated apoptotic markers in old indirect flight muscles, which potentially contribute to the age-related decrease in muscle nuclei. We also developed aging clock models that predict an animal’s age from single-nucleus transcriptomic data. Additionally, we found variances in aging for expressed gene number and cell type identity, with different cell types being differentially affected by different aging features. CONCLUSION The AFCA is a valuable resource and will be of interest to the aging research community. It provides an important and timely resource for studying aging and age-related diseases. It has the potential to serve as a reference of whole-organism aging that can be used as a baseline for exploring different age-related diseases and understanding how different longevity perturbations increase life span at a cellular resolution. The ease of creating whole-fly aging atlases makes D. melanogaster a key model organism for examining the intersection of genetics, cell biology, and physiology going forward. We have developed a user-friendly data portal and provided access at the CELLxGENE. All resources can be accessed at https://hongjielilab.org/afca/ . The Aging Fly Cell Atlas. The AFCA includes single-nucleus transcriptomes of 868,000 nuclei across the Drosophila life span. Males and females were sequenced separately. We characterized 163 distinct cell types, developed aging clock models, and combined four aging features to rank the aging rate of different cell types. [Figure created using Biorender]
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.adg0934
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2023
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
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