SEARCH · PubMed Health

Results for “Senescent fibroblasts”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources

PubMedDate not supplied

Differentiation of primary and secondary fibroblasts in cell culture systems.

As a function of the advancing development of Valo chicken, C3H mice, BN rats, and man in the embryonic, juvenile, adolescent, and senescent phases, stem cells and fibroblasts in the connective tissues of skin and lung differentiate along an 11-stage differentiation sequence in five compartments of the fibroblast stem cell system, when studied in primary ex vivo-in vitro systems. In the fibroblast stem cell system, three stem cells develop in the stem cell compartment along the cell lineage S1-S2-S3, three mitotic fibroblasts (MF) differentiate along the sequence MF I-MF II-MF III in the fibroblast progenitor compartment, three postmitotic fibroblasts (PMF) proceed in the fibroblast maturing compartment along the row PMF IV-PMF V-PMF VI. PMF VI is the terminally differentiated end cell of the fibroblast stem cell system. After a species- and tissue-specific period of high metabolic activity, PMF VI either dies as PMF VIIa in the fibroblast apoptosis compartment or transforms as PMF VIIb in the fibroblast transforming compartment. The reiterated appearance of the 11 cell types in primary stem cell and fibroblast populations and the reiterated age-related changes in the cell type composition of the primary stem cell and fibroblast populations make it very likely that stem cell, mitotic and postmitotic fibroblast equivalents exist in vivo and that age-related changes of the frequencies of the stem cell and fibroblast equivalents result from the progressing differentiation of stem cell, mitotic, and postmitotic fibroblast equivalents along the 11 stage differentiation sequence in the fibroblast equivalent stem cell system in vivo. Secondary fibroblast populations derived from connective tissue of prenatal and postnatal skin of Valo chicken, C3H mice, BN rats, and man, including the normal embryonic human lung fibroblast cell line WI38, were also found to develop along a terminal stem cell sequence. Thus, secondary fibroblast populations in vitro constitute a representative material for studies of general and special issues of cell biology, such as terminal differentiation, aging, apoptosis, and transformation, as long as stem cell system-specific concepts and methods are employed in such investigations.

Animals↗

PubMed2000

Replicative senescence and oxidant-induced premature senescence. Beyond the control of cell cycle checkpoints.

Normal human diploid fibroblasts (HDFs) undergo replicative senescence inevitably in tissue culture after a certain number of cell divisions. A number of molecular changes observed in replicative senescent cells occur in somatic cells during the process of aging. Genetic studies on replicative senescence indicate the control of tumor suppression mechanisms. Despite the significance of replicative senescence in aging and cancer, little is known about the central cause of the complex changes observed in replicative senescent cells. The interest in the phenomenon has intensified in recent years, since damaging agents, certain oncogenes and tumor suppressor genes have been found to induce features of senescence in early passage young HDFs or in immortalized tumor cells. The reported features of senescence are summarized here in order to clarify the concept of replicative senescence or premature senescence. The experimental results of extending the replicative life span by reducing ambient oxygen tension or by N-tert-butyl-alpha-phenylnitrone (PBN) argue a role of oxidative damage in replicative senescence. By inducing premature senescence with a pulse treatment of H2O2, we can study the role of the cell cycle checkpoint proteins p53, p21, p16 and Rb in gaining each feature of senescence. Although p53 and Rb control G1 arrest and Rb appears to control cell enlargement, activation of the senescent associate beta-galactosidase, loss of cell replication and multiple molecular changes observed in premature senescent or replicative senescent cells are likely controlled by mechanisms beyond the cell cycle checkpoints.

Animals↗

PubMed1991

Senescent cells fail to express cdc2, cycA, and cycB in response to mitogen stimulation.

Senescent human diploid fibroblasts (HDF) contain no detectable cdc2 mRNA or p34cdc2 protein. Similarly, young quiescent HDF have only low levels of cdc2 mRNA and protein. After serum stimulation, quiescent HDF accumulate increasing amounts of cdc2 mRNA and protein and go through DNA synthesis and mitosis. In contrast, serum-stimulated senescent HDF fail to accumulate detectable amounts of cdc2 mRNA and protein and fail to enter S phase. Mitosis is likewise deficient in senescent cells even when they have been induced to synthesize DNA by simian virus 40 large tumor antigen. Since p34cdc2 or its homologues appear to be required for DNA synthesis and mitosis in eukaryotes, a lack of these molecules in serum-stimulated senescent HDF could be an important reason for their inability to enter S phase or mitosis. Nuclear microinjection of cdc2 DNA into senescent HDF causes rounding up of the cells but no induction of DNA synthesis. Since cyclins A and B are important cofactors of the protein kinase activity of p34cdc2 or its homologues, we analyzed expression of these genes in serum-stimulated senescent HDF and determined that they contain little or no cycA or cycB mRNA. These deficiencies may be relevant to the lack of DNA synthesis and mitosis in senescent HDF.

Amino Acid Sequence↗

PubMed2001

Id1 regulation of cellular senescence through transcriptional repression of p16/Ink4a.

The Id family of helix-loop-helix (HLH) transcriptional regulatory proteins does not possess a basic DNA-binding domain and functions as a negative regulator of basic HLH transcription factors. Id proteins coordinate cell growth and differentiation pathways within mammalian cells and have been shown to regulate G(1)-S cell-cycle transitions. Although much recent data has implicated Id1 in playing a critical role in modulating cellular senescence, no direct genetic evidence has been reported to substantiate such work. Here we show that Id1-null primary mouse embryo fibroblasts undergo premature senescence despite normal growth profiles at early passage. These cells possess increased expression of the tumor-suppressor protein p16/Ink4a but not p19/ARF, and have decreased cyclin-dependent kinase (cdk) 2 and cdk4 kinase activity. We also show that Id1 is able to directly inhibit p16/Ink4a but not p19/ARF promoter activity via its HLH domain, and that Id1 inhibits transcriptional activation at E-boxes within the p16/Ink4a promoter. Our data provide, to our knowledge, the first genetic evidence for a role for Id1 as an inhibitor of cellular senescence and suggest that Id1 functions to delay cellular senescence through repression of p16/Ink4a. Because epigenetic and genetic abrogation of p16/Ink4a function has been implicated in the evolution of several human malignancies, we propose that transcriptional regulation of p16/Ink4a may also provide a mechanism for the dysregulation of normal cellular growth controls during the evolution of human malignancies.

Animals↗

PubMed2005

Chronically increased oxidative stress in fibroblasts from Alzheimer's disease patients causes early senescence and renders resistance to apoptosis by oxidative stress.

It is well established that oxidative stress is involved in several neurodegenerative disorders, including Alzheimer's disease (AD). Study of the induction and consequences of oxidative stress in the peripheral tissues of the familial AD patients can help to elucidate the inherent abnormalities and the mechanism of pathogenesis of this disease. AD fibroblasts have been used as a model to investigate the underlying mechanisms of oxidative stress. In our study, we used AD fibroblasts from six different donors who are either at high risk of developing AD or have already been diagnosed with AD to study the effect of oxidative stress in comparison with the effect on non-AD normal human fibroblast. Oxidative stress was induced by a brief exposure of the cells to 250microM H(2)O(2) followed by incubation in normal conditions. Neuronal loss due to oxidative stress is a characteristic of Alzheimer's patients; however, our results showed that AD fibroblasts were more resistant to oxidative stress compared to non-AD fibroblasts. Measurement of reactive oxygen species (ROS) indicated that AD fibroblasts produced more ROS than did non-AD NHF cells either in basal conditions or after induction of oxidative stress. Furthermore, we found that expression of p21 was significantly higher in AD cells than in non-AD cells and expression of Bax, a pro-apoptotic protein was downregulated/absent in AD cells during normal or under conditions of external oxidative stress. Further experiments revealed that mitochondria in AD cells moved to the peri-nuclear region following induction of oxidative stress. Thus, these results suggest that AD fibroblasts are chronically exposed to oxidative stress that may trigger senescent phenotype, making AD cell resistant to apoptosis by external oxidative stress.

Alzheimer Disease↗

PubMed2004

DNA damage checkpoint kinase Chk2 triggers replicative senescence.

Telomere shortening in normal human cells causes replicative senescence, a p53-dependent growth arrest state, which is thought to represent an innate defence against tumour progression. However, although it has been postulated that critical telomere loss generates a 'DNA damage' signal, the signalling pathway(s) that alerts cells to short dysfunctional telomeres remains only partially defined. We show that senescence in human fibroblasts is associated with focal accumulation of gamma-H2AX and phosphorylation of Chk2, known mediators of the ataxia-telangiectasia mutated regulated signalling pathway activated by DNA double-strand breaks. Both these responses increased in cells grown beyond senescence through inactivation of p53 and pRb, indicating that they are driven by continued cell division and not a consequence of senescence. gamma-H2AX (though not Chk2) was shown to associate directly with telomeric DNA. Furthermore, inactivation of Chk2 in human fibroblasts led to a fall in p21(waf1) expression and an extension of proliferative lifespan, consistent with failure to activate p53. Thus, Chk2 forms an essential component of a common pathway signalling cell cycle arrest in response to both telomere erosion and DNA damage.

Blotting, Western↗

PubMed2004

No increase in senescence-associated beta-galactosidase activity in Werner syndrome fibroblasts after exposure to H2O2.

Normal human diploid fibroblasts (HDFs) exposed to a single H(2)O(2) subcytotoxic stress display features of premature senescence, termed stress-induced premature senescence (SIPS). In this work, our aim was to study SIPS in Werner syndrome (WS) fibroblasts, derived from a patient with WS, a disease resembling accelerated aging. The subcytotoxic dose for WS fibroblasts was found to be inferior to that of normal HDFs, indicating WS fibroblasts are more sensitive to hydrogen peroxide than normal HDFs. SA beta-gal activity has been shown to occur both in vitro and in vivo, and we studied the proportion of WS cells positive for SA beta-gal. Intriguingly, the percentage of positive cells did not increase with the dose of H(2)O(2) used. Contrary to other HDFs, the DNA-binding activity of p53 in WS fibroblasts did not increase in SIPS. We found, based on our results, that WS fibroblasts feature an altered stress response and do not reach SIPS from H(2)O(2). We suggest that the proportion of cells that in normal HDFs would enter SIPS instead die in WS fibroblasts. Last, we propose that aging derives from a loss of integrity of the chromatin structure, which occurs faster in WS patients.

Aging↗

PubMed1996

Characterization of senescence- and apoptosis-dependent forms of terminin as derived from a precursor found in replicating and nonreplicating cells.

Previously we have reported the production of a monoclonal antibody (Mab 1.2) which recognizes a cytoplasmic protein, terminin, in three different molecular weights: 90 (Tp90), 60 (Tp60), and 30 kDa (Tp30) forms. Further characterization shows that Tp90 is found in young growing and nongrowing quiescent fibroblasts, while Tp60 is found in permanently growth-arrested senescent fibroblasts and Tp30 in cells committed to undergo programmed cell death (apoptosis). In tissue, Tp90 is found in embryonic brain; later, in neonatal brain after terminal differentiation is completed, only Tp60 is found. Tp30 is found in crude liver fractions extracted without the protective action of protease inhibitors. In all these circumstances, Tp90 is mostly seen in the detergent-soluble fraction, while Tp60 and Tp30 are detergent-insoluble. We now report that in cultured fibroblasts, as well as in tissues such as brain and liver, Tp60 and Tp30 are derived from the Tp90 polypeptide, indicated by the fact that only the Tp90 species is identified by both immunoblotting and immunoprecipitation assays, when the cell or tissue extracts are prepared in the presence of protease inhibitors. Further evidence shows that immunoprecipitation of in vitro translation products from brain, liver, and cultured fibroblasts also present a single band of Tp90 polypeptide. Pulse-chase experiments show that during apoptosis, Tp90 is processed to Tp60, and eventually to Tp30. However, when the total protein extracts are fractionated, only Tp90 is found in the detergent-soluble fraction, with diminishing quantities during the time course of apoptosis, and Tp30, in contrast, is found as the only protein species in the insoluble fraction, with increasing quantity during the same time course. Newly processed Tp60 is not found in either of the fractions, reflecting its loss during the fractionation procedure. Limited one-dimensional peptide mapping of Tp90 yields three different bands at 30, 28, and 25 kDa, but only the one at 30 kDa is recognized by Mab 1.2. These results lead us to suggest that terminin protein is synthesized in the Tp90 form, and cleaved to lower molecular weight forms depends upon different physiologic conditions, with Tp60 processed in the terminally differentiated or senescent state and rapidly to Tp30 in apoptosis. Our findings further suggest that Tp90's processing to either Tp60 or Tp30 produces insoluble protein forms. Furthermore, the presence of Tp90 in nonapoptotic (either replicating or nonreplicating) cells may reflect the absence of necessary proteolytic action required for the execution of apoptosis. Future experiments will allow us to determine the nature of this proteolytic action, as well as whether this action is due to the autocatalytic action of Tp90 or by other endogenous proteases, and then to determine the significance of this biochemical action in cells.

3T3 Cells↗

PubMed2004

Human fibroblasts require the Rb family of tumor suppressors, but not p53, for PML-induced senescence.

Cellular senescence is a permanent cell cycle arrest that can be triggered by a variety of stresses including short telomeres and activated oncogenes. Promyelocytic leukemia protein (PML) is a central component of the senescence response, and is able to trigger the process when overexpressed in human diploid fibroblasts (HDFs). Senescence induced by PML in HDFs is characterized by a modest increase in p53 levels and activity, the accumulation of hypophosphorylated Rb and a reduced expression of E2F-dependent genes. To dissect the p53 and Rb family requirements for PML-induced senescence, we used the oncoproteins E6 and E7 from human papillomavirus type 16. We found that the coexpression of E6 and E7 inhibited the growth arrest and senescence induced by PML. In addition, these viral oncoproteins blocked the formation of PML bodies and excluded both p53 and Rb from PML bodies. Expression of dominant-negative p53 alone failed to block PML-induced senescence and expression of E6 only delayed the process. On the other hand, expression of E7 was sufficient to block PML-induced senescence, while an E7 mutant unable to bind Rb did not. Together, these data indicate that PML-induced senescence engages the Rb tumor-suppressor pathway predominantly.

Cellular Senescence↗

PubMed2002

Oncogenic functions of tumour suppressor p21(Waf1/Cip1/Sdi1): association with cell senescence and tumour-promoting activities of stromal fibroblasts.

p21(Waf1/Cip1/Sdi1) is best known as a broad-specificity inhibitor of cyclin/cyclin-dependent kinase complexes, but p21 also interacts with many other regulators of transcription or signal transduction. p21 induction, which is mediated by p53 and by p53-independent mechanisms, is essential for the onset of cell cycle arrest in damage response and cell senescence. The effects of p21 knockout in mice and its expression patterns in human cancer are consistent with a role for p21 as both a tumour suppressor and an oncogene. Several functions of p21 are likely to promote carcinogenesis and tumour progression. These include endoreduplication and abnormal mitosis that develop in tumour cells after release from p21-induced growth arrest, the ability of p21 to inhibit apoptosis through several different mechanisms, and its ability to stimulate transcription of secreted factors with mitogenic and anti-apoptotic activities. The latter effects of p21 show close resemblance to paracrine activities of senescent cells and to tumour-promoting functions of stromal fibroblasts. Therapeutic strategies targeting the oncogenic consequences of p21 expression may provide a new approach to chemoprevention and treatment of cancer.

Animals↗

PubMed2003

Aging-associated increase of gelsolin for apoptosis resistance.

Gelsolin, a Ca(2+)-dependent actin regulatory protein, was recently suggested to participate in apoptosis regulation. In this study, we found that the level of gelsolin is elevated in senescent human diploid fibroblasts (HDFs) and also in the tissues of old rats, i.e., in the liver, kidney, heart, spleen, stomach, and brain, etc. The ubiquitous increase of gelsolin in the aged organs and cells led us to assume that it might be related with one of the cardinal senescent phenotypes, aging-associated apoptosis resistency. Thus, we tested the sensitivity of senescent cells to apoptosis by menadione, an apoptosis-inducing agent, before and after the down-regulation of gelsolin. The down-regulation of gelsolin in senescent HDFs, independently of Bcl-2 family expression, resulted in an increased sensitivity to menadione-induced apoptotic cell death. The observed ubiquitous increase of gelsolin in the senescent states of cells and tissues, and the increased sensitivity to apoptosis-induction by gelsolin down-regulation, suggests that gelsolin would be partly responsible for age-related apoptosis resistance.

Adaptation, Psychological↗

PubMed1995

A biomarker that identifies senescent human cells in culture and in aging skin in vivo.

Normal somatic cells invariably enter a state of irreversibly arrested growth and altered function after a finite number of divisions. This process, termed replicative senescence, is thought to be a tumor-suppressive mechanism and an underlying cause of aging. There is ample evidence that escape from senescence, or immortality, is important for malignant transformation. By contrast, the role of replicative senescence in organismic aging is controversial. Studies on cells cultured from donors of different ages, genetic backgrounds, or species suggest that senescence occurs in vivo and that organismic lifespan and cell replicative lifespan are under common genetic control. However, senescent cells cannot be distinguished from quiescent or terminally differentiated cells in tissues. Thus, evidence that senescent cells exist and accumulate with age in vivo is lacking. We show that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture. This marker was expressed by senescent, but not presenescent, fibroblasts and keratinocytes but was absent from quiescent fibroblasts and terminally differentiated keratinocytes. It was also absent from immortal cells but was induced by genetic manipulations that reversed immortality. In skin samples from human donors of different age, there was an age-dependent increase in this marker in dermal fibroblasts and epidermal keratinocytes. This marker provides in situ evidence that senescent cells may exist and accumulate with age in vivo.

Adult↗

PubMed2001

Clusterin/apolipoprotein J is a novel biomarker of cellular senescence that does not affect the proliferative capacity of human diploid fibroblasts.

Normal human fibroblasts have a limited replicative potential in culture and eventually reach a state of irreversible growth arrest, termed senescence. In a previous study aiming to identify genes that are differentially regulated during cellular senescence we have cloned clusterin/apolipoprotein J (Apo J), a 80 kDa secreted glycoprotein. In the current report we pursue our studies and show that senescence of human diploid fibroblasts is accompanied by up-regulation of both Apo J mRNA and protein levels, but with no altered biogenesis, binding partner profile or intracellular distribution of the two Apo J forms detected. To analyze the causal relationship between senescence and Apo J protein accumulation, we stably overexpressed the Apo J gene in primary as well as in SV40 T antigen-immortalized human fibroblasts and we showed no alteration of the proliferative capacity of the transduced cells. Despite previous reports on tumor-derived cell lines, overexpression of Apo J in human fibroblasts did not provide protection against apoptosis or growth arrest induced by hydrogen peroxide. Overall, our results suggest that Apo J overexpression does not induce senescence but it is rather a secondary consequence of the senescence phenotype. To our knowledge this is the first report that provides a functional analysis of human Apo J during replicative senescence.

Antigens, Differentiation↗

PubMed2000

Posttranslational modifications of p53 in replicative senescence overlapping but distinct from those induced by DNA damage.

Replicative senescence in human fibroblasts is absolutely dependent on the function of the phosphoprotein p53 and correlates with activation of p53-dependent transcription. However, no evidence for posttranslational modification of p53 in senescence has been presented, raising the possibility that changes in transcriptional activity result from upregulation of a coactivator. Using a series of antibodies with phosphorylation-sensitive epitopes, we now show that senescence is associated with major changes at putative regulatory sites in the N and C termini of p53 consistent with increased phosphorylation at serine-15, threonine-18, and serine-376 and decreased phosphorylation at serine-392. Ionizing and UV radiation generated overlapping but distinct profiles of response, with increased serine-15 phosphorylation being the only common change. These results support a direct role for p53 in signaling replicative senescence and are consistent with the generation by telomere erosion of a signal which shares some but not all of the features of DNA double-strand breaks.

Cell Line↗

PubMed2005

The p400 E1A-associated protein is a novel component of the p53 --> p21 senescence pathway.

Adenovirus E1A-associated p400 belongs to the SWI2/SNF2 family of chromatin remodeling proteins. Here, we report that p400 is a component of the p53-p21(WAF1/CIP1/sid1) pathway, regulating the p21 transcription and senescence induction program. Acute depletion of p400 expression by shRNA (short hairpin RNA) synthesis led to premature senescence of untransformed human fibroblasts, whose features include G1 arrest, p21 induction, senescence-associated heterochromatic foci (SAHF), and beta-gal staining. Importantly, p400shRNA-induced premature senescence phenotypes were rescued by coexpression of p53-shRNA or p21-shRNA. Furthermore, p400 complex colocalized with p53 on the p21 promoter. These data suggest that the p400 complex inhibits p53 --> p21 transcription and the development of premature senescence.

Cell Cycle Proteins↗

PubMed1995

Alteration of DNA and RNA binding activity of human telomere binding proteins occurs during cellular senescence.

The loss of telomere sequences during in vitro and in vivo aging suggests that mechanisms affecting telomere length may have important consequences in cellular senescence. In this study, we have found that the activity of single-stranded telomere binding proteins is increased in nuclear extracts prepared from senescent human diploid fibroblasts compared to actively growing cells. Since single-stranded telomere binding proteins are closely related to RNA binding proteins, we examined the binding activity of several major RNA binding proteins to RNA by uv cross-linking. The level of activity was greatly diminished and the overall pattern of uv cross-linked products were altered in extracts prepared from senescent cells. Furthermore, Western analysis revealed a concurrent decrease in senescent extracts of the protein level for many RNA binding proteins, including those which bind to telomere sequence. Although the reduction in the level of these proteins parallels the reduced activity in RNA binding, the paradoxical increased telomere binding activity exhibited by extracts from older cells suggests a complex relationship between these proteins with RNA and DNA. Moreover, the reduced RNA binding activity of these proteins indicates that the biochemical function of several RNA binding proteins is compromised during cellular senescence, raising an intriguing possibility that a change in pre-mRNA metabolism may contribute to the multitude of changes in gene expression observed in cellular senescence.

Base Sequence↗

PubMed2006

Accumulation of senescent cells in mitotic tissue of aging primates.

Cellular senescence, a stress induced growth arrest of somatic cells, was first documented in cell cultures over 40 years ago, however its physiological significance has only recently been demonstrated. Using novel biomarkers of cellular senescence we examined whether senescent cells accumulate in tissues from baboons of ages encompassing the entire lifespan of this species. We show that dermal fibroblasts, displaying markers of senescence such as telomere damage, active checkpoint kinase ATM, high levels of heterochromatin proteins and elevated levels of p16, accumulate in skin biopsies from baboons with advancing age. The number of dermal fibroblasts containing damaged telomeres reaches a value of over 15% of total fibroblasts, whereas 80% of cells contain high levels of the heterochromatin protein HIRA. In skeletal muscle, a postmitotic tissue, only a small percentage of myonuclei containing damaged telomeres were detected regardless of animal age. The presence of senescent cells in mitotic tissues might therefore be a contributing factor to aging and age related pathology and provides further evidence that cellular senescence is a physiological event.

Aging↗

PubMed1999

Effects of an acidic fibroblast growth factor fragment analog on learning and memory and on medial septum cholinergic neurons in senescence-accelerated mice.

We examined the effects of repeated subcutaneous injections of an acidic fibroblast growth factor fragment analog, [Ala16] acidic fibroblast growth factor (1-29), on learning and memory and on the choline acetyltransferase immunoreactivity of forebrain neurons in senescence-accelerated mice. One group of accelerated senescence-prone mice (accelerated senescence-prone-8) received [Ala16] acidic fibroblast growth factor (1-29), whereas the other group of accelerated senescence-prone-8 mice and a group of accelerated senescence-resistant mice (control) received vehicle solution. Injections began at three weeks after birth and were given weekly for 10 months. In a passive avoidance test, the mean retention latency at three, six and nine months of age was significantly longer in controls (vehicle-treated accelerated senescence-resistant-1) and acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 than in vehicle-treated accelerated senescence-prone-8 mice, and the latency in acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice was significantly shorter than that in controls only at nine months of age. In the Morris water maze task, the mean latency to climb onto the platform was significantly longer in acidic fibroblast growth factor fragment- and vehicle-treated accelerated senescence-prone-8 mice than in controls. However, the mean latency in the third and fourth trial blocks was significantly shorter for acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 than for vehicle-treated accelerated senescence-prone-8 mice. In the probe trials, controls and acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice spent significantly more time in the quadrant in which the platform had previously been located than in the other three quadrants. In acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice, the density of medial septum neurons intensely stained for choline acetyltransferase was significantly greater than that in vehicle-treated accelerated senescence-prone-8 mice, but significantly less than that in controls. The results indicate that the beneficial effect of [Ala16] acidic fibroblast growth factor (1-29) on learning and memory function in accelerated senescence-prone-8 mice may be related to a preservation of function in medial septum cholinergic neurons.

Aging↗