The circadian rhythm controls telomeres and telomerase activity

Chen, Wei-Dar; Wen, Ming‐Shien; Shie, Shian-Sen; Lo, Yu‐Lun; Wo, Hung‐Ta; Wang, Chun‐Chieh; Hsieh, I‐Chang; Lee, Tsong‐Hai; Wang, Chao-Yung

doi:10.1016/j.bbrc.2014.07.138

Cited by 71 publications

(64 citation statements)

References 32 publications

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“…The pathway Z scores, indicating the relative degree of activation (positive Z score) or inhibition (negative Z score) of the total of 17 coherently-regulated pathways are represented in Figure 8B. Corroborating our multiple observations of an aberrant aging process in the GIT2KO mice we found consistent and significant GIT2KO-specific alterations in aging-related pathways linked to clock gene disruption: ‘ Mitochondrial dysfunction’ [90]; ‘ AMPK Signaling’ [91]; ‘ P2Y Purinergic Receptor Signaling pathway’ [92]; ‘ P70S6K Signaling’ [93]; ‘ Telomerase Signaling pathway’ [94]; ‘ Superpathway of Cholesterol Biosynthesis’ [95]; ‘ PI3K/AKT Signaling pathway’ [96]. In the context of these multiple interconnected pathways there are also a group of inter-related pathways linking immune cell function (‘ PKCθ Signaling in T Lymphocytes’ , ‘ CD28 Signaling in T Helper Cells’ , ‘ iCOS-iCOSL Signaling in T Helper Cells ’) with Ephrin receptor signaling and clathrin-mediated endocytic subcellular trafficking [97].…”

Section: Resultssupporting

confidence: 62%

“…Nearly all of the coherent and commonly-controlled signaling pathways were strongly linked to cellular clock control mechanisms, e.g. ‘ Mitochondrial Dysfunction’ [90], ‘ AMPK Signaling’ [91], ‘ P70S6K Signaling’ [93], ‘Telomerase Signaling ’ [94], ‘ Superpathway of Cholesterol Biosynthesis’ [95] and ‘ PI3K/AKT Signaling’ [96]. Additional GIT2KO multi-immune tissue signaling pathways also demonstrated multiple functional data corpi links as ‘ P2Y Purinergic Receptor Signaling’ has been shown to strongly control the AMPK signaling pathway [92].…”

Section: Discussionmentioning

confidence: 99%

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Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption

Siddiqui

Lustig²,

Carter³

et al. 2017

Aging

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Recent research has proposed that GIT2 (G protein-coupled receptor kinase interacting protein 2) acts as an integrator of the aging process through regulation of ‘neurometabolic’ integrity. One of the commonly accepted hallmarks of the aging process is thymic involution. At a relatively young age, 12 months old, GIT2−/− mice present a prematurely distorted thymic structure and dysfunction compared to age-matched 12 month-old wild-type control (C57BL/6) mice. Disruption of thymic structure in GIT2−/− (GIT2KO) mice was associated with a significant reduction in the expression of the cortical thymic marker, Troma-I (cytokeratin 8). Double positive (CD4+CD8+) and single positive CD4+ T cells were also markedly reduced in 12 month-old GIT2KO mice compared to age-matched control wild-type mice. Coincident with this premature thymic disruption in GIT2KO mice was the unique generation of a novel cervical ‘organ’, i.e. ‘parathymic lobes’. These novel organs did not exhibit classical peripheral lymph node-like characteristics but expressed high levels of T cell progenitors that were reflexively reduced in GIT2KO thymi. Using signaling pathway analysis of GIT2KO thymus and parathymic lobe transcriptomic data we found that the molecular signaling functions lost in the dysfunctional GIT2KO thymus were selectively reinstated in the novel parathymic lobe – suggestive of a compensatory effect for the premature thymic disruption. Broader inspection of high-dimensionality transcriptomic data from GIT2KO lymph nodes, spleen, thymus and parathymic lobes revealed a systemic alteration of multiple proteins (Dbp, Tef, Per1, Per2, Fbxl3, Ddit4, Sin3a) involved in the multidimensional control of cell cycle clock regulation, cell senescence, cellular metabolism and DNA damage. Altered cell clock regulation across both immune and non-immune tissues therefore may be responsible for the premature ‘aging’ phenotype of GIT2KO mice.

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Section: Resultssupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption

Siddiqui

Lustig²,

Carter³

et al. 2017

Aging

View full text Add to dashboard Cite

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“…TERT mRNA expression has also been reported to oscillate with the circadian rhythm [144]. In mice, deficiency of the clock gene CLOCK has been demonstrated to cause lower telomerase activity, loss of rhythmicity in TERT mRNA expression, and shorter telomeres [144].…”

Section: Telomeres Metabolism and Circadian Rhythmsmentioning

confidence: 99%

“…In mice, deficiency of the clock gene CLOCK has been demonstrated to cause lower telomerase activity, loss of rhythmicity in TERT mRNA expression, and shorter telomeres [144]. Similarly, hospital physicians who work a regular day time pattern have regular and rhythmical circadian oscillation of telomerase activity, while physicians who work a shift pattern in the emergency department lose the normal circadian rhythms of telomerase activity [144]. This dysregulation of telomerase activity may contribute to accelerated ageing and be linked to the higher risk seen in shift workers for a variety of health conditions [145].…”

Section: Telomeres Metabolism and Circadian Rhythmsmentioning

confidence: 99%

“…Taken together, these findings indicate that the circadian regulation of telomerase activity and Mg 2+ homeostasis may play an important role in health, disease, and ageing [144,147]. In light of the twin role of telomerase and Mg 2+ in telomere maintenance and oxidative resilience, circadian disruption could impair the homeostasis and synchronization between telomerase activity and localisation, local [Mg 2+ ], DNA replication, and redox balance.…”

Section: Telomeres Metabolism and Circadian Rhythmsmentioning

confidence: 99%

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Telomere Homeostasis: Interplay with Magnesium

Maguire

Neytchev

Talwar

et al. 2018

IJMS

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Telomere biology, a key component of the hallmarks of ageing, offers insight into dysregulation of normative ageing processes that accompany age-related diseases such as cancer. Telomere homeostasis is tightly linked to cellular metabolism, and in particular with mitochondrial physiology, which is also diminished during cellular senescence and normative physiological ageing. Inherent in the biochemistry of these processes is the role of magnesium, one of the main cellular ions and an essential cofactor in all reactions that use ATP. Magnesium plays an important role in many of the processes involved in regulating telomere structure, integrity and function. This review explores the mechanisms that maintain telomere structure and function, their influence on circadian rhythms and their impact on health and age-related disease. The pervasive role of magnesium in telomere homeostasis is also highlighted.

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Mechanisms of breast cancer risk in shift workers: association of telomere shortening with the duration and intensity of night work

et al. 2017

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Occupational factors such as shiftwork and especially night work that involves disruption of the circadian rhythm may contribute to increased breast cancer risk. Circadian disruption may also affect telomere length (TL). While short TL generally is associated with increased cancer risk, its association with breast cancer risk is inconclusive. We suggest that working schedules might be an important factor in assessment of effects of TL on breast cancer risk. Moreover, telomere shortening might be a potential mechanism for night work‐related breast cancer. In this study, effects of shift work on TL and its association with breast cancer risk were investigated in a nested breast cancer case–control study of Norwegian nurses. TL was assessed by qPCR in DNA from 563 breast cancer patients and 619 controls. Here, we demonstrate that TL is affected by intensive night work schedules, as work with six consecutive night for a period of more than 5 years was associated with decreased telomere lengths (−3.18, 95% CI: −6.46 to −0.58, P = 0.016). Furthermore, telomere shortening is associated with increased breast cancer risk in workers with long periods of consecutive night shifts. Thus, nurses with longer telomere lengths had a lower risk for breast cancer if they had worked more than four (OR: 0.37, 95% CI: 0.16–0.79, P = 0.014) or five (OR: 0.31, 95% CI: 0.10–0.83, P = 0.029) consecutive night shifts for a period of 5 years or more. These data suggest that telomere shortening is associated with the duration and intensity of night work and may be a contributing factor for breast cancer risk among female shift workers.

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The circadian rhythm controls telomeres and telomerase activity

Cited by 71 publications

References 32 publications

Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption

Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruption

Telomere Homeostasis: Interplay with Magnesium

Mechanisms of breast cancer risk in shift workers: association of telomere shortening with the duration and intensity of night work

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