Intermittent fasting attenuates CNS inflammaging - rebalancing the transposonome DOI Creative Commons
Mitchell J Cummins, Ethan T Cresswell, Doug W. Smith

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 12, 2025

Abstract A hallmark of CNS aging is sterile, chronic, low-grade neuroinflammation. Understanding how the develops chronic inflammation necessary to achieve extended healthspan. Characterisation neuroinflammatory molecular triggers remains limited. Interventions that reduce neuroinflammation and extend health lifespan could be useful in this regard. One such intervention intermittent fasting (IF), but IF impacts insufficiently understood. To address this, we performed deep RNA-sequencing on young, middle-aged, old, mouse regions. Additionally, sequenced spinal cord animals subject adult lifelong IF. We found most differentially expressed genes (DEGs) at middle age were region specific (~ 50–84%), whilst effect weakened 18–72%) old age, suggesting emergence a more general global profile. DEGs from all regions enriched for inflammatory immune ontologies. Surprisingly, SC was aging- neuroinflammation-impacted both ages, with by far highest number DEGs, largest net increase expression transposable elements (TEs), greatest enrichment immune-related ontologies, generally larger increases gene expression. Overall, normal upregulation sensors non-self, DNA/RNA, activation inflammasomes, cGAS-STING1 interferon response genes, across CNS. Whilst still developed an profile SC, average lower ~ 50% compared age-matched controls. IF-specific apparent, also acts separate, potentially targetable, pathways those impacted aging. Expression disease associated microglia, phagocytic exhaustion, STING1, inflammasome decreased Significantly, TE reversed decrease. In summary, find hotspot, attenuates neuroinflammaging rebalancing transposonome.

Язык: Английский

RNA‐mediated heterochromatin formation at repetitive elements in mammals DOI Creative Commons
Nikolaos Stamidis, Jan J. Żylicz

The EMBO Journal, Год журнала: 2023, Номер 42(8)

Опубликована: Фев. 27, 2023

The failure to repress transcription of repetitive genomic elements can lead catastrophic genome instability and is associated with various human diseases. As such, multiple parallel mechanisms cooperate ensure repression heterochromatinization these elements, especially during germline development early embryogenesis. A vital question in the field how specificity establishing heterochromatin at achieved. Apart from trans-acting protein factors, recent evidence points a role different RNA species targeting repressive histone marks DNA methylation sites mammals. Here, we review discoveries on this topic predominantly focus methylation, piRNAs, other localized satellite RNAs.

Язык: Английский

Процитировано

11
HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity DOI
Kate L. Morling, Mohamed ElGhazaly,

R Milne

и другие.

Journal of General Virology, Год журнала: 2025, Номер 106(1)

Опубликована: Янв. 13, 2025

Human immunodeficiency virus (HIV) is an exemplar virus, still the most studied and best understood a model for mechanisms of viral replication, immune evasion pathogenesis. In this review, we consider earliest stages HIV infection from transport virion contents through cytoplasm to integration genome into host chromatin. We present holistic virus-host interaction during pivotal stage infection. Central process capsid. The last 10 years have seen transformation in way understand capsid structure function. review key discoveries our latest thoughts on as dynamic regulator innate chromatin targeting. also accessory proteins Vpr Vpx because they are incorporated particles where collaborate with capsids manipulate defensive cellular responses argue that effective regulation uncoating immunity define pandemic potential pathogenesis, how comparison different lineages can reveal what makes lentiviruses special.

Язык: Английский

Процитировано

0
Recurrent oncogenic ZC3H18 mutations stabilize endogenous retroviral RNA DOI Creative Commons
Tanzina Tanu, Anna M. Cox,

Jennifer Karlow

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Endogenous retroviral (ERV) RNA is highly expressed in cancer, although the molecular causes and consequences remain unknown. We found that ZC3H18 (Z18), a component of multiple nuclear surveillance complexes, has recurrent truncating mutations cancer. show Z18 trunc are oncogenic plays an evolutionarily conserved role ERV RNA. In zebrafish, expedited melanoma onset promoted specific accumulation mutant human cell lines from Cancer Cell Line Encyclopedia also higher levels engineered cells, enhanced more than loss one copy, indicating dominant negative activity. directly bound stabilized Notably, expression was sufficient to expedite oncogenesis zebrafish model, which first evidence we aware transcripts can play functional Our work illuminates mechanism for elevated cancer supports aberrant broadly oncogenic.

Язык: Английский

Процитировано

0
Expression of LINE-1 elements is required for preimplantation development and totipotency DOI Creative Commons

Ru Ma,

Nan Xiao, Na Liu

и другие.

Genes & Diseases, Год журнала: 2025, Номер unknown, С. 101555 - 101555

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Intermittent fasting attenuates CNS inflammaging - rebalancing the transposonome DOI Creative Commons
Mitchell J Cummins, Ethan T Cresswell, Doug W. Smith

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 12, 2025

Abstract A hallmark of CNS aging is sterile, chronic, low-grade neuroinflammation. Understanding how the develops chronic inflammation necessary to achieve extended healthspan. Characterisation neuroinflammatory molecular triggers remains limited. Interventions that reduce neuroinflammation and extend health lifespan could be useful in this regard. One such intervention intermittent fasting (IF), but IF impacts insufficiently understood. To address this, we performed deep RNA-sequencing on young, middle-aged, old, mouse regions. Additionally, sequenced spinal cord animals subject adult lifelong IF. We found most differentially expressed genes (DEGs) at middle age were region specific (~ 50–84%), whilst effect weakened 18–72%) old age, suggesting emergence a more general global profile. DEGs from all regions enriched for inflammatory immune ontologies. Surprisingly, SC was aging- neuroinflammation-impacted both ages, with by far highest number DEGs, largest net increase expression transposable elements (TEs), greatest enrichment immune-related ontologies, generally larger increases gene expression. Overall, normal upregulation sensors non-self, DNA/RNA, activation inflammasomes, cGAS-STING1 interferon response genes, across CNS. Whilst still developed an profile SC, average lower ~ 50% compared age-matched controls. IF-specific apparent, also acts separate, potentially targetable, pathways those impacted aging. Expression disease associated microglia, phagocytic exhaustion, STING1, inflammasome decreased Significantly, TE reversed decrease. In summary, find hotspot, attenuates neuroinflammaging rebalancing transposonome.

Язык: Английский

Процитировано

0