Factors Controlling Growth and Age Involution of the Rat Thymus

Bellamy, D.; Hinsull, S. M.; Phillips, J. G.

doi:10.1093/ageing/5.1.12

Cited by 19 publications

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“…The thymus also gradually regresses with age (Miller, 1979). The involution of the human thymus at puberty has been attributed to androgenic steroids (Bellamy et al, 1976). Several reports suggest that the immune system is influenced by sex hormones (Eidinger and Garett, 1972).…”

Section: Introductionmentioning

confidence: 99%

Influence of age, castration, and testosterone on T cell subsets in healthy and leukemia grafted mice

Aboudkhil¹,

Zaîd

Henry³

et al. 2003

Biology of the Cell

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The distribution of T cell subsets in pubertal (2 months) and post-pubertal (10 months) mice showed a significant decrease in the percentage of CD4+ splenocytes and peripheral blood lymphocytes (PBL) with age, unlike the percentage of CD8+ cells in PBL, which remained unchanged. The change in the distribution of T cell subsets in the spleen and blood occurred in 2 months old castrated mice, as in 10 months old animals. P388 tumor grew better in post-pubertal and in castrated mice than in young mice. The intact mice survived longer than the castrated ones. The relative number of CD4+, CD8+ and CD2+ splenocytes was lower in transplanted intact mice than that in controls. The CD8+ and CD2+ subsets in the blood of 2 months transplanted mice were higher than those in controls, whereas in PBL, in 10 months old and castrated mice, the T lymphocyte subsets remain unchanged. Depo-testosterone (DT) injection strongly reduced weight and tumor growth in all the intact and castrated animals. A significant correlation is observed between the tumor weight and testosterone level in the plasma of the 2 months old DT treated mice. Moreover, DT injection induced a significant increase in the percentage of blood CD8+ cells in all the batches. These data indicate that physiologically, androgens affect the age-related distribution of lymphocyte T subsets and suggest that they slow down tumor growth, besides causing a direct effect, through an immunological process.

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Section: Introductionmentioning

confidence: 99%

Influence of age, castration, and testosterone on T cell subsets in healthy and leukemia grafted mice

Aboudkhil¹,

Zaîd

Henry³

et al. 2003

Biology of the Cell

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“…However, it is difficult to explain the timing of the process in humans, especially when it starts, except by assuming that sex hormones must play an important role. And castration can slow down the rate of thymic involution (30,32), even though in mice it does not influence the point in time where involution begins (32). It has, moreover, been reported that partial thymic regeneration could be induced in a 46-yearold human volunteer who was placed on a regimen of recombinant human growth hormone and pharmaceutical grade dehydroepiandrosterone for 1 month (33).…”

Section: Introductionmentioning

confidence: 99%

The Spanish flu as a worst case scenario?

Moxnes¹,

Christophersen²

2008

Microbial Ecology in Health and Disease

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For preparation of pandemic plans for the H5N1 bird flu virus, it has been common practice among health authorities in several countries to use crude death figures from the Spanish flu pandemic as a worst case scenario. This has been done without taking into consideration either what is known about the molecular biology of malignant influenza viruses or the detailed statistical information that is available about the Spanish flu pandemic, as regards the variation of death risk as a function of age and also as regards the different behavior of the virus during successive pandemic waves. There is no scientific basis for the assumption that a new pandemic influenza virus cannot be worse than the Spanish flu virus. However, if we hypothetically assume recurrence of a pandemic influenza virus with virulence and transmissibility properties identical to the Spanish flu virus, but belonging to a subtype other than those that have been circulating in human populations since 1918, it will be unrealistic to assume that the older part of the population will be immune against a type of virus that their immune system has never encountered before. Therefore we have attempted to estimate what might have happened by counterfactually assuming that individuals in 1918 had not been immunized earlier against H1 (or H1N1) influenza viruses that were circulating before 1890. An overview is given of age-related changes in immunological factors that may affect the age-specific mortality in different age groups, and also expected consequences for the mortality in different age groups of mitochondrial DNA aging per se. Extrapolations for age-specific death rate have been made for four different scenarios, giving lower and upper boundaries for what might have happened if nobody had been immune when the 1918Á1920 pandemic started. For the first (lower boundary) scenario the age-specific death rate is increasing up to the age of 30 and is assumed (very unrealistically) to be constant thereafter. For the second scenario the age-specific death rate is monotonically increasing as a function of age according to an almost cubic functionality. For the third (upper boundary) scenario the agespecific death rate is increasing exponentially with age. For the third scenario the mortality of the world population becomes 0.3. Thus 30% of the world population could have been killed by the Spanish flu virus, had nobody been immune when the pandemic started. For the fourth scenario the mortality by age due to the virus mimics the traditional mortality by age in a population. The fifth scenario is identical with scenario 3, except that it is also counterfactually assumed that the wave 2 virus came first. For this scenario, it is found that as much as 80% of the total world population in 1918 might have been killed by the Spanish flu virus.

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“…Postnatally, the thymus increases in size, with expansion of the cortex and medulla, reaching a maximum size at around 10 weeks of age. Following sexual maturation, the thymus begins to shrink, and its weight and volume gradually decrease thereafter [1,2].…”

mentioning

confidence: 99%

“…Ten areas were randomly selected in the histological sections from more than 4 pet/pet and normal thymuses each. All values were averaged and reported as number per mm 2 . Differences between normal and pet/pet rats were assessed as described above.…”

mentioning

confidence: 99%

“…4A-D and 5A). It has been reported that many mitotic cells are present in the thymuses of newborn rats and mice, with the percentage of cycling cells increasing transiently around the time of birth and decreasing to adult values by about 2 weeks of age [2,5]. Indeed, in normal rats, the number of BrdU-incorporating cells was highest at birth, gradually decreasing thereafter.…”

mentioning

confidence: 99%

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Postnatal Development of Hypoplastic Thymus in Semi-Lethal Dwarf pet/pet Males

Chiba

Suzuki

Aoyama

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. The petit rat (pet/pet) is a new semi-lethal dwarf mutant with anomalies in the thymus and testes, defects inherited as a single autosomal recessive trait. At birth, these pet/pet rats show low birth weight and extremely small thymuses; at 140 days of age, their thymuses show abnormal involution. In the present study, we examined early postnatal development of hypoplastic pet/pet thymuses. In addition to being hypoplastic at birth, pet/pet thymus growth was almost completely impaired during the early postnatal period. As shown by cellular incorporation of BrdU, the mitotic activity was lower in pet/pet than in normal thymuses, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that apoptosis occurred more often in pet/pet than in normal thymus cells during the first few days after birth. These results indicate that postnatal development of the hypoplastic pet/pet thymus is defective due to the reduced proliferation and increased apoptosis of thymic cells. The rodent thymus develops as a thymic primordium from the endoderm of the third pharyngeal pouch and from the mesenchyme of the neural crest derived from the third and fourth pharyngeal pouches [7]. Postnatally, the thymus increases in size, with expansion of the cortex and medulla, reaching a maximum size at around 10 weeks of age. Following sexual maturation, the thymus begins to shrink, and its weight and volume gradually decrease thereafter [1, 2].We have previously described pet/pet rats of the PET strain; these rats are characterized by postnatal semi-lethality, severe dwarfism from birth, testis anomalies, and markedly small thymuses (Fig. 1), all of which are controlled by a recessive mutation (pet) [4]. Newborn pet/pet rats were smaller in size, and they had very small thymuses. Relative weights (absolute weight/brain weight) of various organs were significantly lower in 140-day-old pet/pet rats than in age-matched normal rats, whereas the thymus was especially smaller in the former. Histologically, 140 day-old pet/pet thymuses contained both cortex and medulla compartments, but both were quite small, and abnormal thymic follicles were observed in the subcapsular region [4]. Because pet/pet thymuses are smaller at birth and degenerate earlier than normal thymuses, we examined the postnatal development of pet/pet thymuses in the present study.All experimental procedures and care of animals were performed in accordance with the guidelines of the Animal Care Committee of Nippon Veterinary and Life Science University. We utilized pet/pet male rats, identified by their low birth weight, and normal (+/pet or +/+) males of the PET strain; all animals were fed and maintained in our laboratory as described in a previous report [4]. At least 4 pet/ pet and normal males each were euthanized by ether overdoses at 0, 1, 3, 7, 12, and 21 days of age. Thymuses were removed from all rats, weighed, fixed in 10% phosphatebuffered formalin, and processed for paraffin sectioning as described previously [4,9,11]. Sections (thickness, ...

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Factors Controlling Growth and Age Involution of the Rat Thymus

Cited by 19 publications

References 0 publications

Influence of age, castration, and testosterone on T cell subsets in healthy and leukemia grafted mice

Influence of age, castration, and testosterone on T cell subsets in healthy and leukemia grafted mice

The Spanish flu as a worst case scenario?

Postnatal Development of Hypoplastic Thymus in Semi-Lethal Dwarf pet/pet Males

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