Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution

Abstract

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across the organism remain unclear. Here, we present the Aging Fly Cell Atlas, a single-nucleus transcriptomic map of the whole aging Drosophila . We characterized 163 distinct cell types and performed an in-depth analysis of changes in tissue cell composition, gene expression, and cell identities. We further developed aging clock models to predict fly age and show that ribosomal gene expression is a conserved predictive factor for age. Combining all aging features, we find distinctive cell type–specific aging patterns. This atlas provides a valuable resource for studying fundamental principles of aging in complex organisms.

DrosophilaNeuronal Glucose 6 Phosphatase is a Modulator of Neuropeptide Release that Regulates Muscle Glycogen Stores via FMRFamide Signaling

“…We took advantage of the chemoconnectomics resource reported by Deng and colleagues, who generated a series of GAL4 knock-in lines for many NP receptor genes, including FMRFaR (Deng et al, 2019). In adult flies, FMRFaR 2A-GAL4 is strongly expressed in the jump muscle, with moderate expression in the CNS, while no expression was found in other tissues (flight muscle, reproductive system, fat body, gut etc; Figure 6A), a finding consistent with expression profiles reported in the aging fly cell atlas (Lu et al, 2023). We acquired a FMRFaR mutant strain (FMRFaR MB04659 ) and examined the amount of muscle glucose and glycogen in wild type and homozygous receptor mutant flies (Figure 6B).…”

Integrated multi-omics single cell atlas of the human retina

“…Complement pathways have been shown to play important roles in the pathogenesis of age-related macular degeneration (AMD) [42][43][44][45][46][47] , and alterations in steroid hormone homeostasis have been linked to glaucoma 48, 49 . In contrast, the common suppressed pathways included ribosome, cytoplasmic translation, mitochondrial gene expression, and ribonucleoprotein complex assembly, aligning with findings in a fly aging study 50 (Fig. 6D, Extended Data Fig.…”

A single-cell 3D spatiotemporal multi-omics atlas fromDrosophilaembryogenesis to metamorphosis

“…Genes whose expression level showed the strongest positive correlation with CytoTRACE scores were enriched in cell differentiation-related and ribosome protein genes (Figure S4H-I and Table S6) . The latter has been previously reported as indicators of both differentiation potential (reviewed in Ref 33 ) and aging 10 . Conversely, genes whose expression level most negatively correlated with CytoTRACE scores included specific markers of differentiated tissues (e.g., GABAergic neuron-specific marker Rdl 34 and hemocyte-specific marker Ppn 35 ) (Figure S4H) .…”

“…Drosophila melanogaster has long been a fundamental model organism for genetics and developmental biology research. Recent single-cell multi-omics studies have highlighted the versatility of Drosophila in characterizing transcriptomic and epigenomic dynamics of individual cells during embryogenesis 4,5 , tissue development 6–8 , tissue regeneration 9 , and systemic aging 10 . These studies generated rich resources for dissecting the multi-omics profiles of various tissues at single cell precision across developmental stages.…”