Functional, transcriptional, and microbial shifts associated with healthy pulmonary aging in rhesus macaques

Rhoades, Nicholas S; Davies, M.; Lewis, Sloan A.; Cinco, Isaac R; Kohama, Steven G.; Messaoudi, Ilhem; Winthrop, Kevin; Fuss, Cristina; Mattison, Julie A.; Spindel, Eliot R.; Messaoudi, Ilhem

doi:10.1016/j.celrep.2022.110725

“…To determine how these changes relate to the nongravid gut microbiome, we compared our findings to those reported for healthy, age-matched, nongravid (e.g., nonpregnant) female macaques living in the same primate center and sampled during the same year ( 33 ). The overall composition of the nongravid microbiome was distinct from that of the perinatal gut microbiome at both time points (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To address this limitation, we carried out a cross-sectional analysis and compared the microbial communities detected during pregnancy and the postpartum period to those of healthy nongravid females living in the same facility and surveyed during the same window of time using the same experimental approaches (data set extracted from reference 33 ). This comparison indicated a significant impact of pregnancy on the maternal microbiome.…”

Section: Discussionmentioning

confidence: 99%

Taxonomic and Functional Shifts in the Perinatal Gut Microbiome of Rhesus Macaques

Rhoades

¹

,

Cinco

²

,

Hendrickson

³

et al. 2022

Self Cite

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“…In fact, age-associated immune cell type enrichment has also been observed in two independent studies of macaque lungs. One study found increased mast cells, plasma cells, and CD8+ T cells in aged lung tissue ( Ma et al, 2020b ), while the other found increased alveolar and interstitial macrophage numbers in bronchoalveolar lavages of old macaques ( Rhoades et al, 2022 ). The significance of the shift in cellular composition of the aged lungs in relation to the appearance of aging traits remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Lack of evidence for increased transcriptional noise in aged tissues

Ibáñez-Solé

¹

,

Ascensión

²

,

Araúzo‐Bravo

³

et al. 2022

eLife

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Aging is often associated with a loss of cell type identity that results in an increase in transcriptional noise in aged tissues. If this phenomenon reflects a fundamental property of aging remains an open question. Transcriptional changes at the cellular level are best detected by single-cell RNA sequencing (scRNAseq). However, the diverse computational methods used for the quantification of age-related loss of cellular identity have prevented reaching meaningful conclusions by direct comparison of existing scRNAseq datasets. To address these issues we created Decibel, a Python toolkit that implements side-to-side four commonly used methods for the quantification of age-related transcriptional noise in scRNAseq data. Additionally, we developed Scallop, a novel computational method for the quantification of membership of single cells to their assigned cell type cluster. Cells with a greater Scallop membership score are transcriptionally more stable. Application of these computational tools to seven aging datasets showed large variability between tissues and datasets, suggesting that increased transcriptional noise is not a universal hallmark of aging. To understand the source of apparent loss of cell type identity associated with aging, we analyzed cell type-specific changes in transcriptional noise and the changes in cell type composition of the mammalian lung. No robust pattern of cell type-specific transcriptional noise alteration was found across aging lung datasets. In contrast, age-associated changes in cell type composition of the lung were consistently found, particularly of immune cells. These results suggest that claims of increased transcriptional noise of aged tissues should be reformulated.

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“…In fact, age-associated immune cell type enrichment has also been observed in two independent studies of macaque lungs. One study found increased mast cells, plasma cells and CD8+ T cells in aged lung tissue ( Ma et al, 2020b ), while the other found increased alveolar and interstitial macrophage numbers in bronchoalveolar lavages of old macaques ( Rhoades et al, 2022 ). The significance of the shift in cellular composition of the aged lungs in relation to the appearance of aging traits remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Lack of evidence for increased transcriptional noise in aged tissues

Ibáñez-Solé

¹

,

Ascensión

²

,

Araúzo-Bravo

³

et al. 2022

Preprint

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Aging is often associated with a loss of cell type identity that results in an increase in transcriptional noise in aged tissues. If this phenomenon reflects a fundamental property of aging remains an open question. Transcriptional changes at the cellular level are best detected by single-cell RNA sequencing (scRNAseq). However, the diverse computational methods used for the quantification of age-related loss of cellular identity have prevented reaching meaningful conclusions by direct comparison of existing scRNAseq datasets. To address these issues we created Decibel, a Python toolkit that implements side-to-side four commonly used methods for the quantification of age-related transcriptional noise in scRNAseq data. Additionally, we developed Scallop, a novel computational method for the quantification of membership of single cells to their assigned cell type cluster. Cells with a greater Scallop membership score are transcriptionally more stable. Application of these computational tools to seven aging datasets showed large variability between tissues and datasets, suggesting that increased transcriptional noise is not a universal hallmark of aging. To understand the source of apparent loss of cell type identity associated with aging, we analyzed cell type-specific changes in transcriptional noise and the changes in cell type composition of the mammalian lung. No robust pattern of cell type-specific transcriptional noise alteration was found across aging lung datasets. In contrast, age-associated changes in cell type composition of the lung were consistently found, particularly of immune cells. These results suggest that claims of increased transcriptional noise of aged tissues should be reformulated.

show abstract

Functional, transcriptional, and microbial shifts associated with healthy pulmonary aging in rhesus macaques

Cited by 11 publications

References 107 publications

Taxonomic and Functional Shifts in the Perinatal Gut Microbiome of Rhesus Macaques

Taxonomic and Functional Shifts in the Perinatal Gut Microbiome of Rhesus Macaques

Lack of evidence for increased transcriptional noise in aged tissues

Lack of evidence for increased transcriptional noise in aged tissues

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