In situ evidence of cellular senescence in Thymic Epithelial Cells (TECs) during human thymic involution

Barbouti, Alexandra; Evangelou, Konstantinos; Pateras, Ioannis S.; Papoudou‐Bai, Alexandra; Patereli, Amalia; Stefanaki, Kalliopi; Rontogianni, Dimitra; Muñoz‐Espín, Daniel; Kanavaros, Panagiotis; Gorgoulis, Vassilis G.

doi:10.1016/j.mad.2018.02.005

Cited by 32 publications

(25 citation statements)

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“…Relevant to the above analysis is our previous study, in which we showed for the first time in human thymuses that TECs but not lymphoid cells exhibit oxidative DNA damage in samples from aged individuals [63]. These findings provide in situ evidence the TECs but not lymphoid cells are sensitive to ROS [63].…”

Section: Oxidative Stress In Age-related Thymic Involutionsupporting

confidence: 57%

“…In this context of robust thymopoiesis, an inherent deficiency of TECs in CAT may render these cells more vulnerable to ROS and could contribute to early thymic atrophy (Figure 1), thereby providing evidence to explain, at least in part, why the thymus is affected more rapidly in comparison to other organs [39]. Relevant to the above analysis is our previous study, in which we showed for the first time in human thymuses that TECs but not lymphoid cells exhibit oxidative DNA damage in samples from aged individuals [63]. These findings provide in situ evidence the TECs but not lymphoid cells are sensitive to ROS [63].…”

Section: Oxidative Stress In Age-related Thymic Involutionmentioning

confidence: 64%

“…Given that oxidative stress can induce senescence and senescent cells accumulate in tissues as a consequence of aging [57], we investigated whether senescence is present during age-related thymic involution in human archival (formalin fixed and paraffin embedded) material [63]. For this purpose, we used a novel, biotinylated Sudan Black B analogue termed GL13 (SenTraGor™) that specifically reacts with lipofuscin, a hallmark of senescent cells [41,44,63,146,147]. Indeed, a number of TECs were detected mainly within the medulla and especially in the vicinity of Hassall's corpuscles that exhibited dense cytoplasmic GL13 positivity in the majority of aged samples whereas staining in sections from infants was negative [63] ( Figure 3).…”

Section: Cellular Senescence In Age-related Thymic Involutionmentioning

confidence: 99%

“…Considering that (1 st ) oxidative stress has been linked to both the induction of cellular senescence and thymic involution and (2 nd ) aging is characterized by accumulation of senescent cells as well as a decline in thymus function, it is not unreasonable to assume that cellular senescence may exert a critical role in the induction of thymic involution, with oxidative stress being the common denominator. Indeed, recent evidence, from human and animal studies, supports this notion [62,63]. The scope of this review is to summarize data regarding the role of oxidative stress in both thymic involution and cellular senescence.…”

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confidence: 97%

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Implications of Oxidative Stress and Cellular Senescence in Age-Related Thymus Involution

Barbouti

Vasileiou

Evangelou

et al. 2020

Oxidative Medicine and Cellular Longevity

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The human thymus is a primary lymphoepithelial organ which supports the production of self-tolerant T cells with competent and regulatory functions. Paradoxically, despite the crucial role that it exerts in T cell-mediated immunity and prevention of systemic autoimmunity, the thymus is the first organ of the body that exhibits age-associated degeneration/regression, termed “thymic involution.” A hallmark of this early phenomenon is a progressive decline of thymic mass as well as a decreased output of naïve T cells, thus resulting in impaired immune response. Importantly, thymic involution has been recently linked with cellular senescence which is a stress response induced by various stimuli. Accumulation of senescent cells in tissues has been implicated in aging and a plethora of age-related diseases. In addition, several lines of evidence indicate that oxidative stress, a well-established trigger of senescence, is also involved in thymic involution, thus highlighting a possible interplay between oxidative stress, senescence, and thymic involution.

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Section: Oxidative Stress In Age-related Thymic Involutionsupporting

confidence: 57%

Section: Oxidative Stress In Age-related Thymic Involutionmentioning

confidence: 64%

Section: Cellular Senescence In Age-related Thymic Involutionmentioning

confidence: 99%

mentioning

confidence: 97%

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Implications of Oxidative Stress and Cellular Senescence in Age-Related Thymus Involution

Barbouti

Vasileiou

Evangelou

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Cellular senescence although represents an age-related process, also occurs during normal development and adult life. The short communication byBarbouti et al, (2018) represents the first in situ evidence linking cellular senescence with human thymic involution. The regulating mechanisms of this age related process are still not fully elucidated, thus the author, by using the novel chemical compound, a Sudan Black-B analogue-SenTraGorTM, demonstrates that cellular senescence occurs during human thymic involution, providing thus further insights in thymus histophysiology (Barbouti et al, 2018).…”

mentioning

confidence: 99%

Where ageing goes nowadays: Mechanisms, pathways, biomarkers and anti-ageing strategies

Gonos

Chondrogianni

Djordjevic

2019

Mechanisms of Ageing and Development

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Although ageing is (still) an inevitable biological process, humans currently are facing an unprecedented increase in their lifespan. However, healthy ageing has a primate above the simple increase in lifespan and thus the current anti-ageing strategies are switching the focus from suppressing ageing to promote successful ageing and healthspan. The main aim is not just to maximize the length of life, but instead to increase the period of life time spent free of detrimental conditions accompanying old age. Discovering fully the fundamental molecular mechanisms and factors underlying the process of ageing and longevity is a prerequisite for developing appropriate strategies for increasing "healthy lifespan". In this respect ageing research nowadays goes to

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Thymus Microenvironment: Maintenance, Ageing and Strategies for Thymus Regeneration Following Damage

Alsharif¹,

Chidgey²

2022

Encyclopedia of Life Sciences

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The thymus is the major site of T‐lymphocyte production. Nonlymphoid elements, referred to as the thymic stroma, create the thymic microenvironment required to govern differentiation, maturation and tolerance induction of haematopoietic precursors into immune‐competent, nonautoreactive T cells. Thymic epithelial cells (TECs) are integral to thymopoiesis but are affected by ageing. From the onset of puberty, a proportional imbalance of TEC subpopulations coincides with a dramatic numerical loss of developing T cells. By middle‐age numerical loss of TECs accompanies further loss of thymocytes. Ongoing functional impediment of bipotent thymic epithelial progenitor cells (TEPC) has been proposed as one possible underlying cause and is more apparent in males. As such, endogenous recovery following thymic damage, such as from chemotherapy, in middle‐aged males relies heavily on proliferation of residual immature and mature TECs than through homeostatic differentiation of bipotent TEPC evident in middle‐aged females. Various strategies have been proposed to enhance thymus recovery following cytoablative therapies; however, thus far, temporary suppression of sex hormone production appears to have the most wide‐ranging impact on enhancing mature TEC replenishment and thymopoiesis. Key Concepts Thymic epithelial cells are critical for T cell development. Single‐cell transcriptomics and mapping identified more TEC subsets than first realised. Mature thymic medullary epithelial cells are essential for the presentation of self‐antigens for central tolerance induction. During age‐related thymus involution, an imbalance in TEC subsets accompanies the numerical loss of developing T cells from the onset of puberty. Postnatal bipotent thymic epithelial progenitor cells (TEPC) undergo functional attenuation from puberty with sexual dimorphism apparent. Increased reliance on activation and proliferation of enduring single‐lineage cortical and medullary TEC precursors for mature TEC maintenance during ageing. Thymic damage induces homeostatic TEC replenishment via bipotent TEPC in middle‐aged females but is restricted to proliferation and differentiation of single lineage progenitors in middle‐aged males. Temporary suppression of sex hormone production as a strategy for thymus regeneration releases the postpubertal TEPC functional block in males. Therapeutic strategies with clinical potential include adoptive transfer of in vitro generated progenitor T cells, exogenous administration of cytokines and growth factors, and temporary sex steroid inhibition.

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In situ evidence of cellular senescence in Thymic Epithelial Cells (TECs) during human thymic involution

Cited by 32 publications

References 34 publications

Implications of Oxidative Stress and Cellular Senescence in Age-Related Thymus Involution

Implications of Oxidative Stress and Cellular Senescence in Age-Related Thymus Involution

Where ageing goes nowadays: Mechanisms, pathways, biomarkers and anti-ageing strategies

Thymus Microenvironment: Maintenance, Ageing and Strategies for Thymus Regeneration Following Damage

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