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Myogenic stem cell commitment probability remains constant as a function of organismal and mitotic age.

Chicken myogenic stem cells can undergo symmetric and asymmetric cell divisions. Symmetric divisions produce two stem cells or two cells committed to terminal muscle differentiation. Asymmetric divisions produce one stem cell and one committed cell. Committed cells undergo four divisions, and their progeny differentiate into postmitotic, biochemically distinct muscle cells, which can be identified immunocytochemically. The control of stem cell commitment was investigated in vitro by means of cell cloning and subcloning experiments, and computer modeling. We found that stem cell commitment is a process which can be modeled as a stochastic event, with a central tendency or probability of 0.2 +/- 0.1. This value is independent of organismal or mitotic age of the stem cells, cell density, or growth in a mitogen-poor environment. Myogenic stem cells stop dividing after approximately 30 divisions in vitro. Since the probability of commitment to terminal differentiation remains below 0.5, clonal senescence and terminal differentiation are separate processes in this system.

Animals↗

Differences between mitotically old and young endometrial tumors.

Human tumors likely differ in their mitotic ages, reflecting how many divisions elapse between the final tumor progenitor cell and surgical removal. We used a rapidly fluctuating CpG (fCpG) methylation clock to infer relative endometrial adenocarcinomas (EAC) mitotic ages. Experimentally, young tumors initiated from single cells show low-diversity, high-variance fCpG distributions with trimodal peaks near 0%, 50%, and 100%, reflecting inherited progenitor methylation states. fCpG methylation becomes polymorphic with divisions, and older tumors exhibit higher diversity, lower variance, and unimodal distributions centered around 50%. Mitotic ages varied across EAC samples. Synchronous hyperplasia and invasive regions generally shared similar ages, and primary-metastatic EAC pairs showed both synchronous and stepwise progression. The Cancer Genome Atlas (TCGA) EACs also showed variable mitotic ages: younger tumors were enriched for proliferation pathways, whereas older tumors showed more immune infiltration, immune-pathway activation, and evidence of T-cell exhaustion. These results show that human tumors can be ranked by mitotic age and suggest that the growth of older cancers is restrained by immune surveillance. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Humans↗

Mitotic index and cell nuclear volume of zona fasciculata externa in processes of postnatal growth of rat adrenals.

Mitotic index and nuclear volume of the zona fasciculata externa have been studied using male and female Wistar rats weighing 20, 50, 100, 250 and 300 g. Adrenal weight of females was greater than of males. Early postnatal growth of adrenals was attained at the expense of intensity of mitotic division. With age mitotic division decreased but cell hypertrophy developed. Cell hypertrophy in females began at an early age and was more marked than in males.

Adrenal Glands↗

Differential effects of age on mitotically active and inactive bone marrow stem cells and splenic T cells in mice.

Young and old BALB/c mice and thymectomized young mice were subjected to continuous exposure of 6-thioguanine (6-TG), and the numbers of their bone marrow spleen colony-forming units (CFU-S) and in vitro culture colony-forming units (CFU-C) and the number and mitogen-induced proliferative activity of their splenic T cells were determined at various time intervals. The results indicated that (a) old mice have seven times more 6-TG-resistant (6-TGr) CFU-S than young mice, (b) the mitogen-induced proliferative activity of 6-TGr T cells is comparable to that of 6-TG-sensitive (6-TGs) T cells of both young and old mice, and (c) 6-TGr CFU-S and T cells are resistant to 6-TG because they are mitotically inactive and not because they are drug-resistant mutants.

Aging↗

Clinical characteristics of placental site trophoblastic tumor (PSTT).

Placental site trophoblastic tumor (PSTT) has been demonstrated to be a rare variant of gestational trophoblastic disease, with only 43 cases of this disorder having been reported in the English language literature since 1976. It is associated with a 20% mortality rate, occurs in young women, is very resistant to standard trophoblastic disease chemotherapy, and is generally treated by hysterectomy. This report describes an additional 5 cases of PSTT, two of whom died of their disease. It aims to clarify the varied clinical characteristics of the condition through a comparative analysis of these patients with those previously reported. Specific factors in the analysis include age, mitotic count, presence of marker hormones, preceding gestational situation, cause of death, survival time from diagnosis, tumor karyotype, and treatment. The study suggests that a preceding term pregnancy, a high mitotic ratio, and an older age group may be associated with a higher mortality rate. It also supports the premise that some patients, with a low mitotic ratio and other favorable histologic features, may be treated conservatively with curettage and very careful follow-up monitoring if they wish to preserve reproductive potential.

Adult↗

Immunohistochemical and electron microscopical studies of mitotic adenohypophysial cells in different ages of rats.

Mitotic rates of the six types of immunohistochemically identifiable adenohypophysial cells were histometrically calculated in colchicine-pretreated male rats 5, 17, 30 and 70 days old. Sections were stained with the antisera against rLH, rFSH, rTSH, oGH, rPRL and pACTH1-39. The mitotic growth rate of the anterior pituitary gland at 30 days of age was much higher than at other times. Mitotic growth rates of GH and PRL cells increased with advancing age, while those of ACTH-TSH- and immunonegative cells decreased with advancing age. LH/FSH cells showed no variation in mitotic growth rate with age. Mitotic cells can be classified into six cell types based on their fine structural properties: (1) agranular cells associated with the folliculo-stellate cells; (2) ambiguous cells with scanty minute secretory granules (50-150 nm in diameter); (3) basophils with a number of small secretory granules (130-200 nm); (4) immature acidophils whose large secretory granules (130-300 nm) are sporadically scattered; (5) acidophils with numerous spherical larger secretory granules (200-300 nm); and (6) prolactin cells with large polymorphic granules. At day 5 there was a high mitotic rate of the agranular and ambiguous cells [types (1) and (2)]; at day 70 a high mitotic rate was found in immature and mature acidophils [types (4) and (5)]. The mitotic rate of basophils (type 3) was high only at day 17 and low at all other times. The mitotic rate of prolactin cells (type 6) showed a slight increment with advancing age. It is concluded that the mitotic rates of the six cell types are age-dependent.

Aging↗

Satellite cell mitotic activity in posthatch turkey skeletal muscle growth.

The relationship between satellite cell mitotic activity and skeletal myofiber growth was examined in Pectoralis thoracicus and Biceps femoris muscles of Large White tom turkeys (Nicholas strain) at 3, 6, 9, 18, and 26 wk of age. Mitotically active satellite cells were labeled with 5-bromo-2'-deoxyuridine (BrdU). Labeled satellite cells were identified on enzymatically isolated myofiber segments using mouse anti-BrdU followed by fluorescein-5-isothiocyanate (FITC) conjugated goat anti-mouse IgG secondary antibodies. Myofiber nuclei (satellite cell nuclei + myonuclei) were counterstained with propidium iodide (PI). Myofiber segment diameter, myofiber segment length, and number of FITC- and PI-labeled nuclei were determined for each segment. At each age interval there was an increase in myofiber diameter, suggesting that the myofibers were growing during the entire experimental period. There was an age-related (P < .001) decrease in satellite cell mitotic activity and an age-related increase (P < .001) in the cytoplasmic volume to nucleus ratio (CNR) from 3 to 26 wk of age. An early phase of myofiber growth, between 3 and 6 wk of age, was characterized by a high level of satellite cell mitotic activity and increased CNR. Between 6 and 9 wk of age, satellite cell mitotic activity decreased, but the CNR showed no change (P > .05). During a late phase of myofiber growth, beyond 9 wk of age, satellite cell mitotic activity continued to decrease and myofiber growth occurred by an increased CNR. This study demonstrated that both Pectoralis thoracicus and Biceps femoris undergo a significant late phase of growth without appreciable production of myonuclei by satellite cell proliferation.

Age Factors↗

Relationships between cytoplasmic microtubular complex, DNA synthesis and cell morphology in mouse embryonic fibroblasts (effects of age, serum deprivation, aphidicolin, cytochalasin B and colchicine).

Aging, aphidicolin, serum deprivation and cytochalasin B induce a decrease in the rate of DNA synthesis, an increase in cell flattening (cell surface increase) and an extension of the cytoplasmic microtubular complex (CMTC). Age and experimental conditions affect the protein content of the cell, but there is no relationship between cell morphology and cell protein content. Serum deprivation, aphidicolin and cytochalasin B are more effective on DNA synthesis and cytoplasmic actin complex (CAC) of late than of early fibroblasts. Despite these facts, the cell morphology of late cells is fairly stable and is not affected by experimental conditions, which exert an "aging effect" upon the cell morphology in earlier cultures. Colchicine acts upon the CMTC, cell morphology and DNA synthesis at all ages of the cultures. It also induces disruption of the CAC, the intensity of the disruption depending on both the length of the treatment and the age of the culture: the sensitivity of the actin-microfilaments to colchicine increases with the mitotic age of the cells. We suggest that the microtubular integrity is needed, but not sufficient, to preserve the organization of the CAC into microfilaments. We propose a logical model comprising feedback loops between the number of the mitotic cycles, the rate of DNA synthesis, the extention rate of the plasma membranes and CMTC in normal fibroblasts. CMTC is associated, in this model, with the expression of negative or positive controls, depending on the grade of its extension (Fig. 9).

Animals↗

Age-related changes in prolactin cell percentage and serum prolactin levels in intact and neonatally gonadectomized male and female rats.

Electron microscopically the percentages of various pituitary cell types were calculated at 30 and 90 days of age. Prolactin cell percentage was more at 90 days of age than at 30 days in both intact male and female rats. No sexual difference was observed in the percentage of prolactin cells at 30 days of age, but at 90 days female pituitaries contained more numerous prolactin cells than males ones. Neonatal ovariectomy did not affect the prolactin cell percentage at 30 days of age, while it lowered the percentage at 90 days. Neonatal orchidectomy did not affect the prolactin cell percentage at both 30 and 90 days of age. Mitotic prolactin cells were more frequently observed in intact female rats at estrus than in intact male rats at 90 days of age. These results shown the presence of the sexual difference in the proliferation of prolactin cells. Serum prolactin levels increased with age in intact male and female rats. In neonatally gonadectomized male and female rats the serum prolactin levels failed to increase at 60 and 90 days of age. In general conclusion, the changes in serum prolactin levels are in line with the changes in prolactin cell population during postnatal development.

Age Factors↗

Effects of continuous intravenous infusion of diethylstilbestrol into pregnant mice on fetus: testicular morphology at fetal and postnatal period.

Diethylstilbestrol was continuously infused into pregnant mice through the tail vein. In male fetus exposed to diethylstilbestrol (DES) from days 15 to 19 of gestation, Leydig cells of the testis were found to be increased in number when examined at 3-60 days of age. Mitotic rate in the interstitial tissue was elevated in 0- to 3-day-old mice exposed prenatally to DES. The ratio of the intertubular space to testis size was greater at 3 days of age than at 1 day in prenatally DES-exposed mice, while in the controls, the rate was lower at 3 days than at 1 day. Spermatogenic activity was lower in DES-exposed adult mice than in the controls, as shown by the spermatogenic index.

Animals↗

Cationized ferritin binding and internalization during in vitro aging of mouse embryonic fibroblasts.

The anionic surface sites of mouse embryo fibroblasts in primary culture, aging in vitro, have been studied using cationized ferritin (CF) as a marker. We have not observed significant differences between early and late cells with respect to CF binding; the labelling is uneven and patchy in both cases. Due to the increase of their surface area with the mitotic age, the total amount of negative charges, per cell, must however be much higher in the late passage cells. Virtually no differences in the rates of CF endocytosis via coated pits, with subsequent delivery to large vacuoles and lysosomes, have again been observed, but there was a cisternal formation from apposed plasma membranes in the late cells. New findings with regard to previous studies with CF concern the capping of the labelled surface components, followed by phagocytosis of the cap material, and the organization of the extracellular matrix in a rather regular network at the periphery of the cells.

Animals↗

The effect of early posthatch nutrition on satellite cell mitotic activity.

Myofiber growth is dependent upon the contribution of new nuclei from the mitotically active satellite cell population. The objective of this study was to examine satellite cell mitotic activity in conjunction with different nutritional paradigms during the early posthatch period. Turkey poults were provided a standard turkey starter diet; the starter diet top-dressed with a hydrated low-fat, highly digestible protein and carbohydrate nutritional hatchling supplement, Oasis; the starter diet top-dressed with Solka-floc dyed green; or no food for the first 3 d posthatch. All birds were fed a standard starter diet during the experimental period. 5-Bromo-2'-deoxyuridine (BrdU) was continuously infused into all treatments (n = 5 all groups) between hatch and 3 d of age. A second group of identically treated poults housed in separate pens (n = 3 to 5) was continuously infused with BrdU between 2 and 9 d of age. Mitotically active satellite cells were identified in the pectoralis thoracicus and quantitated using BrdU immunohistochemistry in combination with computer-based image analysis. Satellite cell mitotic activity was significantly higher (P < or = 0.05) in the birds fed a standard starter diet compared to all other treatments at 3 d posthatch. However, there were no (P > or = 0.05) differences in satellite cell mitotic activity among treatments at 9 d posthatch. The results of the current study suggest that any improvements in meat yield through early nutritional supplementation do not appear to occur through a satellite cell pathway and that there is no compensatory response in the satellite cell population following refeeding after early posthatch starvation.

Age Factors↗

Initiation of oogenesis in the human fetal ovary: ultrastructural and squash preparation study.

Ovaries from 27 human fetuses at less than or equal to 12 weeks' gestational age were examined with electron microscopy and squash preparation studies. The findings demonstrated that meiosis begins in the fetal ovary between 11 and 12 weeks of age. This is several weeks after gonadal sex differentiation, which can be recognized in the testis at 6 weeks. Ovaries at earlier ages included primitive germ cells and oogonia. With advancing fetal age, mitotic activity and germ cell degeneration became increasingly evident. Preleptotene cells were found as early as 9 to 10 weeks, suggesting that meiotic capacity is present soon after gonadal sex differentiation but further progression into meiosis is delayed until some specific inductive influence is exerted.

Female↗