Age-dependent remodeling of rat thymus. Morphological and cytofluorimetric analysis from birth up to one year of age

Quaglino, Daniela; Capri, Miriam; Bergamini, Giovanna; Euclidi, Emanuela; Zecca, Luigi; Franceschi, Claudio; Ronchetti, Ivonne Pasquali

doi:10.1016/s0171-9335(98)80029-0

Cited by 34 publications

(23 citation statements)

References 21 publications

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“…Again, therefore, genetic heterogeneity in outbred populations might be expected to contribute to marked interindividual differences. Careful experiments in the rat have shown that thymic involution cannot be viewed simply as a progressive shrinkage, but as complex remodelling dependent on unknown factors (79), and therefore susceptible to manipulation when these factors are properly identified. One of these factors may be the status of the T cells themselves in the individual; for example, thymic involution is reported not to occur in T cell antigen receptor (TCR)-transgenic mice, leading to the conclusion that successfully matured T cells can maintain thymic integrity (80,81).…”

Section: Thymusmentioning

confidence: 99%

T cells and aging update February 1999

Pawelec¹

1999

Front Biosci

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T cell immunosenescence 218effects of dysregulated immune responses in the elderly by supplementation or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age. FACTORS CONTRIBUTING TO IMMUNO-SENESCENCE HematopoiesisDysregulated hematopoiesis is seen in elderly individuals, raising the possibility that this could contribute to altered immune function in the aged. Hematopoiesis in man may be compromised because of a severely reduced capacity to produce colony stimulating factors (44) and increased production of pro-inflammatory factors such as IL 6 (45), because lower numbers of progenitor cells are present in the BM (46) and because of an age-related decline in proliferative potential of putative haematopoietic stem cells (HSC) (47). In mice, the repopulating potential of murine fetal liver-derived HSC is higher than that of adult BM-derived stem cells (48), suggesting possible aging of the HSC themselves. Normal cells with shorter telomeres possess less remaining replicative capacity than those with longer telomeres (see section 5.2). Accordingly, HSC from adult BM were found to have shorter telomeres than fetal liver-derived or umbilical cord-derived stem cells, consistent with aging of HSC (49). Telomere lengths decreased on culture despite low level expression of telomerase in these cells (50,51), although the rate of basepair loss per population doubling of cells in culture was lower during the first two weeks, when telomerase was upregulated, than in the next two, when it was downregulated (52). The telomerase expressed is therefore functionally active but may not be able to completely maintain telomere length in aging HSC cells. True embryonic stem cells (ESC), on the other hand, which may really be immortal, do retain high levels of telomerase activity (53). On the other hand, ESC from telomerase-knockout mice show gradual telomere shortening over many population doublings (PD) resulting in slowing and eventual cessation of growth (54). Certain animals which do not downregulate telomerase manifest a permanent growth phase and little or no senescence (55,56).

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Section: Thymusmentioning

confidence: 99%

T cells and aging update February 1999

Pawelec¹

1999

Front Biosci

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“…Many factors such as hormonal deficiencies, dietary impairment, exposure to stress or bacterial endotoxins have all been suggested as instrumental for increasing the physiological involution of the thymus which is seen at advanced age. The age-associated regression in size, weight and cellularity of the thymus as well as an increased apoptosis of the thymic cortex are considered to be the most important contributing factors to thymic cell death [47] . Regression of the thymus can be induced by pinealectomy [48] and, conversely, the process can be reversed by melatonin administration [49] .…”

Section: Melatonin and Thymusmentioning

confidence: 99%

Immunomodulation by Melatonin: Its Significance for Seasonally Occurring Diseases

Srinivasan

Spence²,

Trakht

et al. 2008

Neuroimmunomodulation

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Melatonin is not only synthesized by the pineal gland but also in many other organs and tissues of the body, particularly by lymphoid organs such as the bone marrow, thymus and lymphocytes. Melatonin participates in various functions of the body, among which its immunomodulatory role has assumed considerable significance in recent years. Melatonin has been shown to be involved in the regulation of both cellular and humoral immunity. Melatonin not only stimulates the production of natural killer cells, monocytes and leukocytes, but also alters the balance of T helper (Th)-1 and Th-2 cells mainly towards Th-1 responses and increases the production of relevant cytokines such as interleukin (IL)-2, IL-6, IL-12 and interferon-γ. The regulatory function of melatonin on immune mechanisms is seasonally dependent. This fact may in part account for the cyclic pattern of symptom expression shown by certain infectious diseases, which become more pronounced at particular times of the year. Moreover, melatonin-induced seasonal changes in immune function have also been implicated in the pathogenesis of seasonal affective disorder and rheumatoid arthritis. The clinical significance of the seasonally changing immunomodulatory role of melatonin is discussed in this review.

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“…(24) A unique characteristic of both organs is their early involution and the remodeling of the cellular microenvironment and lymphocyte subsets, a phenomenon recognized as a major component of immunosenescence. (29)(30)(31)(32) Aging is a complex phenotype resulting from the continuous, lifelong adaptation of the body to unrepaired molecular and cellular damage to the soma caused by a variety of external and internal agents. The process leads to a progressively decreased capability to cope with stressors and to an age-related, increased risk of morbidity and mortality.…”

Section: Thymus Involutionmentioning

confidence: 99%

“…Moreover, thymic involution is characterized by a reduction in mitoses associated with an increased number of apoptotic figures. (29) An evolution-based interpretation of thymic involution assumes, within the framework of the ''disposable soma'' theory, that thymus is made to last for a limited period of time, and that it would be a useless waste of energy and resources to maintain its full activity for the entire lifespan. (33) In this perspective, the involution of thymus and bursa of Fabricius can be taken as a paradigmatic example of eco-immunology, in which neuro-endocrinological pathways play a key role.…”

Section: Thymus Involutionmentioning

confidence: 99%

Ecoimmunology: is there any room for the neuroendocrine system?

et al. 2008

Self Cite

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Ecological Immunology assumes that immunological defenses must be minimized in terms of cost (energy expenditure). To reach this goal, a complex and still largely unexplored strategy has evolved to assure survival. From invertebrates to vertebrates, an integrated immune-neuroendocrine response appears to be crucial for the hierarchical redistribution of resources within the body according to the specific ecological demands. Thus, on the basis of experimental data on the intimate relationship between stress and immune responses that has been maintained during evolution, we argue that a broader perspective based on the integration of immune and neuroendocrine responses should be adopted to describe the comprehensive strategy that the body utilizes to adapt to dynamic environmental conditions. We discuss the hypothesis that a bow-tie architecture might be suitable to describe the variety of immune-neuroendocrine inputs that continuously target cells and organs while, at the same time, fulfilling the basic requirement of minimizing the cost of immune-neuroendocrine responses. Bow-tie architectures are able to convert a variety of stimuli (fan in) into a wide range of fine-tuned responses (fan out) by passing through the integrating activity of a core (knot) constituted by a limited number of elements. Finally, we argue that the ecologically negotiated immune-neuroendocrine strategies may have deleterious effects in the post-reproductive period of life when, at least in humans, chronic, low-grade, systemic inflammation develops, in accordance with the antagonistic pleiotropy theory of aging.

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Age-dependent remodeling of rat thymus. Morphological and cytofluorimetric analysis from birth up to one year of age

Cited by 34 publications

References 21 publications

T cells and aging update February 1999

T cells and aging update February 1999

Immunomodulation by Melatonin: Its Significance for Seasonally Occurring Diseases

Ecoimmunology: is there any room for the neuroendocrine system?

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