The differential spatiotemporal expression pattern of shelterin genes throughout lifespan

Wagner, Kay-Dietrich; Ying, Yilin; Leong, Waiian; Jiang, Jie; Hu, Xuefei; Chen, Yi; Michiels, Jean‐François; Lu, Yiming; Gilson, Éric; Wagner, Nicole; Ye, Jing

doi:10.18632/aging.101223

Cited by 22 publications

(18 citation statements)

References 25 publications

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“…Whether telomere shortening concomitant to TRF2 downregulation in skeletal muscle destabilizes the telomere‐ SIRT3 loop, as observed for other loci (Kim et al, ; Robin, Ludlow, et al, ; Robin et al, ), is an interesting hypothesis. Further, if telomere shortens in human tissues, including skeletal muscle (Daniali et al, ), diminution of TRF2, as already reported through lifetime in animal models (e.g., mice, zebrafish; Wagner et al, ), remains to be established in other human tissues. Noteworthy, recent studies focusing on another postmitotic tissue (e.g., heart) also link telomere length and TRF2 level to metabolic changes (Chang et al, , ; Oh et al, ).…”

Section: Discussionmentioning

confidence: 93%

Mitochondrial function in skeletal myofibers is controlled by a TRF2‐SIRT3 axis over lifetime

et al. 2020

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Telomere shortening follows a developmentally regulated process that leads to replicative senescence of dividing cells. However, whether telomere changes are involved in postmitotic cell function and aging remains elusive. In this study, we discovered that the level of the TRF2 protein, a key telomere‐capping protein, declines in human skeletal muscle over lifetime. In cultured human myotubes, TRF2 downregulation did not trigger telomere dysfunction, but suppressed expression of the mitochondrial Sirtuin 3 gene (SIRT3) leading to mitochondrial respiration dysfunction and increased levels of reactive oxygen species. Importantly, restoring the Sirt3 level in TRF2‐compromised myotubes fully rescued mitochondrial functions. Finally, targeted ablation of the Terf2 gene in mouse skeletal muscle leads to mitochondrial dysfunction and sirt3 downregulation similarly to those of TRF2‐compromised human myotubes. Altogether, these results reveal a TRF2‐SIRT3 axis controlling muscle mitochondrial function. We propose that this axis connects developmentally regulated telomere changes to muscle redox metabolism.

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Section: Discussionmentioning

confidence: 93%

Mitochondrial function in skeletal myofibers is controlled by a TRF2‐SIRT3 axis over lifetime

et al. 2020

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“…In addition to regulation of gene expression by telomere length, telomeres, subtelomeres, shelterin proteins and telomerase are all themselves subject to epigenetic regulatory mechanisms [ 79 , 151 ]. Of particular note, in mice and zebrafish the mRNA levels from the genes encoding the six shelterin subunits change with age, in a tissue specific fashion [ 152 ], and it will be exciting to test if these changes may impact age-related pathologies.…”

Section: Telomere Structure and Functionmentioning

confidence: 99%

Epigenetic Mechanisms Impacting Aging: A Focus on Histone Levels and Telomeres

Song

Johnson

2018

Genes

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Aging and age-related diseases pose some of the most significant and difficult challenges to modern society as well as to the scientific and medical communities. Biological aging is a complex, and, under normal circumstances, seemingly irreversible collection of processes that involves numerous underlying mechanisms. Among these, chromatin-based processes have emerged as major regulators of cellular and organismal aging. These include DNA methylation, histone modifications, nucleosome positioning, and telomere regulation, including how these are influenced by environmental factors such as diet. Here we focus on two interconnected categories of chromatin-based mechanisms impacting aging: those involving changes in the levels of histones or in the functions of telomeres.

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“…Zebrafish demonstrate agerelated decline in cognition and perception (reviewed in: Adams and Kafaligonul 2018). Age-related mitochondrial dysfunction and oculopathy (Wang et al 2019), nervous system aging and disease (Van houcke et al 2015), agerelated changes in DNA methylation (Shimoda et al 2014), oncology (Barriuso et al 2015), Peutz-Jeghers syndrome (van der Velden and Haramis 2011), telomere attrition (Wagner et al 2017), osteoarthritis (Hayes et al 2013), osteoporosis (Zhang et al 2018), immune system, and endocrine decline have all been described in zebrafish (Arslan-Ergul and Adams 2014; Beis and Agalou 2020; Carneiro et al 2016). In addition, the endocannabinoid system is well-conserved in zebrafish (reviewed in: Oltrabella et al 2017), thus making them an excellent model to study the effects of both cannabinoids and aging.…”

Section: Introductionmentioning

confidence: 99%

Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio)

et al. 2020

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Consumption of cannabinoid-containing products is on the rise, even during pregnancy. Unfortunately, the long-term, age-related consequences of developmental cannabidiol (CBD) exposure remain largely unknown. This is a critical gap given the established Developmental Origins of Health and Disease (DOHaD) paradigm which emphasizes that stressors, like drug exposure, early in life can instigate molecular and cellular changes that ultimately lead to adverse outcomes later in life. Thus, we exposed zebrafish (Danio rerio) to varying concentrations of CBD (0.02, 0.1, 0.5 μM) during larval development and assessed aging in both the F0 (exposed generation) and their F1 offspring 30 months later. F0 exposure to CBD significantly increased survival (~20%) and reduced size (wet weight and length) of female fish. While survival was increased, the age-related loss of locomotor function was unaffected and the effects on fecundity varied by sex and dose. Treatment with 0.5 μM CBD significantly reduced sperm concentration in males, but 0.1 μM increased egg production in females. Similar to other model systems, control aged zebrafish exhibited increased kyphosis as well as increased expression markers of senescence, and inflammation (p16 ink4ab , tnfα, il1b, il6, and pparγ) in the liver. Exposure to CBD significantly reduced the expression of several of these genes in a dose-dependent manner relative to the age-matched controls. The effects of CBD on size, gene expression, and reproduction were not reproduced in the F1 generation, suggesting the influence on aging was not cross-generational. Together, our results demonstrate that developmental exposure to CBD causes significant effects on the health and longevity of zebrafish.

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The differential spatiotemporal expression pattern of shelterin genes throughout lifespan

Cited by 22 publications

References 25 publications

Mitochondrial function in skeletal myofibers is controlled by a TRF2‐SIRT3 axis over lifetime

Mitochondrial function in skeletal myofibers is controlled by a TRF2‐SIRT3 axis over lifetime

Epigenetic Mechanisms Impacting Aging: A Focus on Histone Levels and Telomeres

Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio)

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