Aging disrupts circadian gene regulation and function in macrophages

Blacher, Eran; Tsai, Connie; Litichevskiy, Lev; Shipony, Zohar; Iweka, Chinyere Agbaegbu; Schneider, Kai Markus; Chuluun, Bayarsaikhan; Heller, H. Craig; Menon, Vilas; Thaiss, Christoph A.; Andreasson, Katrin I.

doi:10.1038/s41590-021-01083-0

Cited by 96 publications

(68 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ovarian cancer models using flow cytometry, we envision its usage in other i.p. studies, such as in the burgeoning focus on tissue resident macrophages [ 60 , 61 , 62 ], and its pairing with other technologies (RNA-seq, ATAC-seq, CyTOF) and cellular characterization methods.…”

Section: Discussionmentioning

confidence: 99%

Minimally Invasive Preclinical Monitoring of the Peritoneal Cavity Tumor Microenvironment

Dunn

et al. 2022

Cancers

View full text Add to dashboard Cite

Intraperitoneal (i.p.) experimental models in mice can recapitulate the process of i.p. dissemination in abdominal cancers and may help uncover critical information about future successful clinical treatments. i.p. cellular composition is studied in preclinical models addressing a wide spectrum of other pathophysiological states such as liver cirrhosis, infectious disease, autoimmunity, and aging. The peritoneal cavity is a multifaceted microenvironment that contains various immune cell populations, including T, B, NK, and various myeloid cells, such as macrophages. Analysis of the peritoneal cavity is often obtained by euthanizing mice and performing terminal peritoneal lavage. This procedure inhibits continuous monitoring of the peritoneal cavity in a single mouse and necessitates the usage of more mice to assess the cavity at multiple timepoints, increasing the cost, time, and variability of i.p. studies. Here, we present a simple, novel method termed in vivo intraperitoneal lavage (IVIPL) for the minimally invasive monitoring of cells in the peritoneal cavity of mice. In this proof-of-concept, IVIPL provided real-time insights into the i.p. tumor microenvironment for the development and study of ovarian cancer therapies. Specifically, we studied CAR-T cell therapy in a human high-grade serous ovarian cancer (HGSOC) xenograft mouse model, and we studied the immune composition of the i.p. tumor microenvironment (TME) in a mouse HGSOC syngeneic model.

show abstract

Section: Discussionmentioning

confidence: 99%

Minimally Invasive Preclinical Monitoring of the Peritoneal Cavity Tumor Microenvironment

Dunn

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…However, amplitudes generally varied more than phases measured relative to population means across subjects in each layer. Amplitudes of circadian rhythms are expected to decrease with age [36], but were not previously known to vary more than phases in similarly-aged young subjects. Finally, dermal rhythm amplitudes were smaller but less variable across subjects, while epidermal rhythms possessed larger amplitudes and were more subject-variable.…”

Section: Discussionmentioning

confidence: 99%

Inter-layer and inter-subject variability of circadian gene expression in human skin

Olmo

Spoerl

Korge

et al. 2022

Preprint

View full text Add to dashboard Cite

The skin is the largest human organ with a circadian clock that regulates its function. Although circadian rhythms in specific functions are known, rhythms in the proximal clock output, gene expression, in human skin have not been thoroughly explored. This work reports circadian gene expression in two skin layers, epidermis and dermis, in a cohort of young, healthy adults, who maintained natural, regular sleep schedules. 10% of the expressed genes showed rhythms at the population level, of which only a third differed between the two layers. Broadly, expression magnitudes of circadian genes were consistent across subjects in each layer. Amplitude and phases of circadian gene expression, however, varied more across subjects than layers, with amplitude being more variable than phases. Expression amplitudes in the epidermis were larger and more subject-variable, while they were smaller and more consistent in the dermis. Core clock gene expression was similar across layers at the population-level, but were heterogeneous in the their variability across subjects. We used this data to identify small sets of biomarkers for internal clock phase in each layer, which consisted of layer-specific non-core clock genes. This work provides a valuable resource to advance our understanding of human skin to realize the potential of circadian medicine as well as a novel methodology to quantify sources of variability in human circadian rhythms.

show abstract

“…Macrophages, as potent immunoregulatory innate immune cells, have a crucial effect on immune defense and regulation of inflammation ( 152 ). It has been highlighted that aging could disrupt circadian gene regulation and function of macrophages ( 153 ). Meanwhile, aging could be reversed by reprogramming glucose metabolism of macrophages and re-establishing youthful immune homeostasis ( 154 ).…”

Section: The Alterations Of Immune Cell Subsets Related To Immunosene...mentioning

confidence: 99%

Immunosenescence, aging and successful aging

Wang

Dong²,

Han³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Aging induces a series of immune related changes, which is called immunosenescence, playing important roles in many age-related diseases, especially neurodegenerative diseases, tumors, cardiovascular diseases, autoimmune diseases and coronavirus disease 2019(COVID-19). However, the mechanism of immunosenescence, the association with aging and successful aging, and the effects on diseases are not revealed obviously. In order to provide theoretical basis for preventing or controlling diseases effectively and achieve successful aging, we conducted the review and found that changes of aging-related phenotypes, deterioration of immune organ function and alterations of immune cell subsets participated in the process of immunosenescence, which had great effects on the occurrence and development of age-related diseases.

show abstract

Aging disrupts circadian gene regulation and function in macrophages

Cited by 96 publications

References 57 publications

Minimally Invasive Preclinical Monitoring of the Peritoneal Cavity Tumor Microenvironment

Minimally Invasive Preclinical Monitoring of the Peritoneal Cavity Tumor Microenvironment

Inter-layer and inter-subject variability of circadian gene expression in human skin

Immunosenescence, aging and successful aging

Contact Info

Product

Resources

About