Aged mice have increased inflammatory monocyte concentration and altered expression of cell-surface functional receptors

Strohacker, Kelley; Breslin, Whitney L; Carpenter, Katie C; McFarlin, Brian K.

doi:10.1007/s12038-011-9169-z

Cited by 20 publications

(19 citation statements)

References 25 publications

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“…There was increased expression of proinflammatory molecules and the activity of basilar membrane macrophages in Sesn2 KO mice. This observation is consistent with previous findings that expressions of genes associated with inflammatory are altered during age-related cochlear degeneration and accompanied by an increase in circulating macrophages (Boggs et al, 1986; Strohacker et al, 2012; Tra et al, 2011). Because excessive inflammation is detrimental to the structure and function of the cochlea (Raphael, 2002), our findings suggest that cochlear inflammation may interact with sensory cell damage and compromise the sensory cell survival.…”

Section: Discussionsupporting

confidence: 93%

Loss of sestrin 2 potentiates the early onset of age-related sensory cell degeneration in the cochlea

Zhang

Sun

et al. 2017

Neuroscience

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Sestrin 2 (SESN2) is a stress-inducible protein that protects tissues from oxidative stress and delays the aging process. However, its role in maintaining the functional and structural integrity of the cochlea is largely unknown. Here, we report the expression of SESN2 protein in the sensory epithelium, particularly in hair cells. Using C57BL/6J mice, a mouse model of age-related cochlear degeneration, we observed a significant age-related reduction in SESN2 expression in cochlear tissues that was associated with early onset hearing loss and accelerated age-related sensory cell degeneration that progressed from the base toward the apex of the cochlea. Hair cell death occurred by caspase-8 mediated apoptosis. Compared to C57BL/6J control mice, Sesn2 KO mice displayed enhanced expression of proinflammatory genes and activation of basilar membrane macrophages, suggesting that loss of SESN2 function provokes the immune response. Together, these results suggest that Sesn2 plays an important role in cochlear homeostasis and immune responses to stress.

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Section: Discussionsupporting

confidence: 93%

Loss of sestrin 2 potentiates the early onset of age-related sensory cell degeneration in the cochlea

Zhang

Sun

et al. 2017

Neuroscience

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“…Induction of a chronic inflammatory state has been associated with aging (87, 88), and inflammation can significantly reduce neurogenesis (89–91). Brain inflammation is characterized by macrophages and microglia producing proinflammatory cytokines (TNFα, IL-1β, and IL-6) during prolonged inflammation.…”

Section: Th Control Of Adult Neurogenesis In the Aging Brainmentioning

confidence: 99%

Thyroid Hormone Signaling and Adult Neurogenesis in Mammals

et al. 2014

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The vital roles of thyroid hormone in multiple aspects of perinatal brain development have been known for over a century. In the last decades, the molecular mechanisms underlying effects of thyroid hormone on proliferation, differentiation, migration, synaptogenesis, and myelination in the developing nervous system have been gradually dissected. However, recent data reveal that thyroid signaling influences neuronal development throughout life, from early embryogenesis to the neurogenesis in the adult brain. This review deals with the latter phase and analyses current knowledge on the role of T3, the active form of thyroid hormone, and its receptors in regulating neural stem cell function in the hippocampus and the subventricular zone, the two principal sites harboring neurogenesis in the adult mammalian brain. In particular, we discuss the critical roles of T3 and TRα1 in commitment to a neuronal phenotype, a process that entails the repression of a number of genes notably that encoding the pluripotency factor, Sox2. Furthermore, the question of the relevance of thyroid hormone control of adult neurogenesis is considered in the context of brain aging, cognitive decline, and neurodegenerative disease.

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“…The failure to efficiently upregulate these markers appears to be linked to changes in autophagy, rather than Atg7 specifically, and may represent a novel role for autophagy in maintaining or regulating functional endocytic pathways that control surface marker trafficking and expression. Aged macrophages also frequently exhibit a reduced expression of surface marker genes and receptors, including MHC II [8, 13] and TLR4 [11]. Upregulation of MHC I and II and coreceptors are crucial for efficient antigen presentation.…”

Section: Discussionmentioning

confidence: 99%

“…Elevated levels of IL-6, TNF-α and IL-1β produced by inflammatory macrophages [14] are also frequently found in the serum and tissues of the elderly, resulting from inflammasome over-activation [35] and increased TLR signalling mediated by ROS and DAMPs released by stressed or dying cells [36]. Increased macrophage numbers are a common feature of aging in both mouse and human models [7, 8]. Accordingly, macrophages from old mice were significantly increased in the blood and spleen, similar to Vav-Atg7 mice.…”

Section: Discussionmentioning

confidence: 99%

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Autophagy Controls Acquisition of Aging Features in Macrophages

Hansen²,

et al. 2015

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Macrophages provide a bridge linking innate and adaptive immunity. An increased frequency of macrophages and other myeloid cells paired with excessive cytokine production is commonly seen in the aging immune system, known as ‘inflamm-aging'. It is presently unclear how healthy macrophages are maintained throughout life and what connects inflammation with myeloid dysfunction during aging. Autophagy, an intracellular degradation mechanism, has known links with aging and lifespan extension. Here, we show for the first time that autophagy regulates the acquisition of major aging features in macrophages. In the absence of the essential autophagy gene Atg7, macrophage populations are increased and key functions such as phagocytosis and nitrite burst are reduced, while the inflammatory cytokine response is significantly increased - a phenotype also observed in aged macrophages. Furthermore, reduced autophagy decreases surface antigen expression and skews macrophage metabolism toward glycolysis. We show that macrophages from aged mice exhibit significantly reduced autophagic flux compared to young mice. These data demonstrate that autophagy plays a critical role in the maintenance of macrophage homeostasis and function, regulating inflammation and metabolism and thereby preventing immunosenescence. Thus, autophagy modulation may prevent excess inflammation and preserve macrophage function during aging, improving immune responses and reducing the morbidity and mortality associated with inflamm-aging.

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Aged mice have increased inflammatory monocyte concentration and altered expression of cell-surface functional receptors

Cited by 20 publications

References 25 publications

Loss of sestrin 2 potentiates the early onset of age-related sensory cell degeneration in the cochlea

Loss of sestrin 2 potentiates the early onset of age-related sensory cell degeneration in the cochlea

Thyroid Hormone Signaling and Adult Neurogenesis in Mammals

Autophagy Controls Acquisition of Aging Features in Macrophages

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