Senescent Changes Research Articles

Effects of early-fruit removal on endogenous cytokinins and abscisic acid in relation to leaf senescence in cotton

Numerous studies have shown that early-fruit removal enhances vegetative growth and development of cotton (Gossypium hirsutum L.). However, few studies have examined changes in leaf senescence and endogenous hormones due to fruit removal. The objective of this study was to determine the correlation between some endogenous phytohormones, particularly the cytokinins and abscisic acid (ABA), and leaf senescence following fruit removal. Cotton was grown in pots and in the field during 2005 and 2006. Two early-fruiting branches were excised from plants at squaring to form the fruit removal treatment while the non-excised plants served as control. Plant biomass, seed cotton yield, cytokinins and ABA levels in main-stem leaves and xylem sap as well as main-stem leaf photosynthetic rate (Pn) and chlorophyll (Chl) concentration were determined after removal or at harvest. Fruit removals increased the leaf area, root and shoot dry weight and plant biomass at 35 days after removal (DAR), whether in potted or field-grown cotton; under field conditions, it also improved plant biomass and seed cotton yield at harvest. The Pn and Chl concentration in excised plants were significantly higher than in control plants from 5 to 35 DAR, suggesting that fruit removal considerably delayed leaf senescence. Fruit-excised plants contained more trans-zeatin and its riboside (t-Z + t-ZR), dihydrozeatin and its riboside (DHZ + DHZR), and isopentenyladenine and its riboside (iP + iPA) but less ABA in both main-stem leaves and xylem sap than control plants from 5 to 35 DAR. These results suggest that removal of early fruiting branches delays main-stem leaf senescence, which can be attributed to increased cytokinin and/or reduced ABA. Cytokinin and ABA are involved in leaf senescence following early fruit removal.

Midface Lift Using A Minimally Invasive Technique and a Novel Absorbable Suture

Midface rejuvenation is a minimally invasive procedure designed to correct early ptosis of the cheeks and deepening nasolabial folds. Implementation of this technique requires a detailed understanding of the anatomy of this region in addition to recognizing the vectors of change that occur over time as one matures. Finally, aesthetic competence and requisite surgical skills are required to restore the midface in a minimally invasive fashion. To describe a new minimally invasive approach to facial rejuvenation using a novel absorbable suture with segmented stabilizers that allows for a superolateral reversal of the senescent changes of the midface. In a case series study, 30 patients with aging changes of the midface signed informed consent to have this procedure done. An incision was made in the preauricular area, followed by hydrodissection with tumescent anesthesia and blunt dissection with the aid of a 4-mm spatula cannula. Two angiocatheters (14GA 3.25 IN, 2.1 x 83 mm, 14 gauge) were tunneled through the malar fat pad and pierced the skin just lateral to the nasolabial fold. The angiocatheter was then removed and the suture tethered to facilitate the proper amount of lifting entirely in the subcutaneous supra-SMAS plane and anchored superolaterally to the temporalis fascia. The segmented stabilizers anchored themselves in multiple directions but ultimately lifted the tissues of the midface. This technique uses the multidirectional segmented stabilizers of the Monograms to counteract the downward displacement of the malar fat pad while simultaneously softening the nasolabial fold. This is a minimally invasive technique that addresses the multiple factors involved in the senescent changes of the midface. Proper patient selection, good aesthetic judgment, and surgical competence are required to restore the midface in a minimally invasive fashion. The objective of this study was to report a novel approach to midfacial rejuvenation using the Monograms. This cross-hatched suture achieves simultaneous malar fat pad elevation and nasolabial fold effacement. The midface lift adds another vital dimension to panfacial augmentation.

Ageing and testicular function in Octodon degus.

The present study analyses cell loss and proliferation which account for the decrease in the number of germ cell populations in the senile male Octodon degus. This is a good model to study ageing in wild animals, since it has recently been incorporated as a laboratory animal but still has a high degree of genetic heterogeneity, thus representing a situation found in natural systems. The cell loss from pachytene spermatocytes to round spermatids is estimated by cell counts in the cross section of seminiferous tubules. DNA testicular synthesis is measured by scintillation counting and the index of labelling of spermatogonia by radioautography of testes comparing sexually mature young animals and senile animals. Other determinations in both groups are testis weight, thickness of the albuginea and tubular wall, daily sperm production, percentage of depleted seminiferous tubules and nuclear cell diameters of germ cells. The results suggest a decrease in the number of cell population in the senile animals resulting from an increase in physiological cell loss coupled with a decreased proliferative spermatogonial activity. There is also a decreased yield of meiosis in terms of round spermatid production. Lowered testosterone levels both in plasma and testicular parenchymal fluid are found in senile animals. All these senescent changes reflect an altered remodelling activity of the seminiferous epithelium and presumably also of Leydig cells.

Cellular senescence in usual type uterine leiomyoma

To evaluate the role of senescence in symptomatic patients with multifibroids. A cohort study. University research laboratory. Eighty-six fibroids collected from 14 patients who underwent myomectomy or hysterectomy. Senescence-associated beta-galactosidase (SA-beta-Gal) stain in fresh-frozen tissue; reverse-transcription polymerase chain reaction (RT-PCR); MicroRNA in situ hybridization (MISH); immunohistochemistry in formalin-fixed paraffin-embedded tissue. Senescence measured by percentage of SA-beta-Gal-positive cells; levels of let-7 microRNAs measured by RT-PCR and MISH; expression of p16(INK4a), Ki-67, HMGA1, and HMGA2 scaled by immunoreactivity. About 58% (48 of 82) of tumors showed significant senescent change (SA-beta-Gal positive) in >10% of the tumor volume. The overall trend was a higher level of senescence in small fibroids and older-aged women. Senescent fibroids were additionally shown to have, high levels of let-7 c, d, and f-2 and a low Ki-67 index. Senescence is a common cellular change in a large proportion of usual type fibroids. Similarly, senescence may explain the variation in growth rates of these tumors, and may prove to be an important molecular and cellular target in prevention of fibroid growth.

Role of high-order aberrations in senescent changes in spatial vision

The contributions of optical and neural factors to age-related losses in spatial vision are not fully understood. We used closed-loop adaptive optics to test the visual benefit of correcting monochromatic high-order aberrations (HOAs) on spatial vision for observers ranging in age from 18 to 81 years. Contrast sensitivity was measured monocularly using a two-alternative forced-choice (2AFC) procedure for sinusoidal gratings over 6 mm and 3 mm pupil diameters. Visual acuity was measured using a spatial 4AFC procedure. Over a 6 mm pupil, young observers showed a large benefit of AO at high spatial frequencies, whereas older observers exhibited the greatest benefit at middle spatial frequencies, plus a significantly larger increase in visual acuity. When age-related miosis is controlled, young and old observers exhibited a similar benefit of AO for spatial vision. An increase in HOAs cannot account for the complete senescent decline in spatial vision. These results may indicate a larger role of additional optical factors when the impact of HOAs is removed, but also lend support for the importance of neural factors in age-related changes in spatial vision.

Cognitive plasticity in adulthood and old age: Gauging the generality of cognitive intervention effects

Interventions enabling aging individuals to fulfill their plastic potential promise to postpone, attenuate, or even reverse the adverse effects of senescent brain changes on cognitive abilities and everyday competence in old age. Based on an overview of the concept of plasticity in lifespan development, we selectively review evidence from cognitive intervention studies and conclude that most of them have failed to observe generalizable performance improvements, as documented by the small size and scope of positive transfer to untrained tasks. We further note that generally accepted criteria for defining transfer distance are lacking, rendering the relevant evidence difficult to interpret. Hence, we propose a taxonomy of transfer distance based on the structure of human intellectual abilities.

Audition and Cognition: Where Lab Meets Clinic

Audition and Cognition: Where Lab Meets Clinic

Ionizing Radiation of Mesenchymal Stem Cells Results in Diminution of the Precursor Pool and Limits Potential for Multilineage Differentiation

Although ionizing radiation is an important treatment modality for a number of malignancies, it can be associated with significant morbidity. The exact mechanisms by which ionizing radiation results in cellular injury remain unknown. Mesenchymal stem cells give rise to a number of tissues including bone, fat, and cartilage and provide an excellent cellular model with which to evaluate the effects of ionizing radiation on cellular survival and function. Rat mesenchymal stem cells were irradiated with 0, 7, and 12 Gy of ionizing radiation and assessed for changes in growth, apoptosis, cell-cycle profile, senescence, differentiation, and gene expression. Ionizing radiation resulted in a significant decrease in cellular proliferation because of increased apoptosis, G2 cell-cycle arrest, and premature senescence. In addition, ionizing radiation caused low-level spontaneous osteoblastic differentiation. Conversely, cellular differentiation in response to lineage-specific culture conditions for bone, fat, and cartilage was markedly decreased in irradiated cells, thereby demonstrating a deficit in the ability of irradiated mesenchymal stem cells to respond to environmental stimuli. Although the majority of mesenchymal stem cells survive injury from ionizing radiation, this injury results in a significant decrease in cellular proliferation. Furthermore, the differentiation potential of irradiated mesenchymal stem cells in response to environmental stimuli is markedly diminished. Thus, the negative effects of ionizing radiation may result from a decreased pool of progenitor cells with limited differentiation potential. Proposed radioprotection strategies aiming to reduce tissue injury should therefore evaluate not only cellular survival but also cellular function.

Early spring leaf out enhances growth and survival of saplings in a temperate deciduous forest

Saplings of many canopy tree species in winter deciduous forests receive the major portion of their light budget for their growing season prior to canopy closure in the spring. This period of high light may be critical for achieving a positive carbon (C) gain, thus contributing strongly to their growth and survival. This study of saplings of Aesculus glabra and Acer saccharum in Trelease Woods, Illinois, USA, tested this hypothesis experimentally by placing tents of shade cloth over saplings during their spring period of high light prior to canopy closure in three consecutive years. Leaf senescence began 16 days (year 0) and 60 days (year 1) earlier for shaded A. glabra saplings than control saplings. No change in senescence occurred for A. saccharum. The annual absolute growth in stem diameter of both species was negligible or negative for shaded saplings, but positive for control saplings. Only 7% of the shaded A. glabra saplings were alive after 2 years, while all control saplings survived for 3 years; only 20% of the shaded A. saccharum saplings survived for 3 years, while 73% of control saplings were alive after the same period. Early spring leaf out is a critical mechanism that allows the long-term persistence of saplings of these species in this winter deciduous forest. Studies and models of C gain, growth, and survival of saplings in deciduous forests may need to take into account their spring phenology because saplings of many species are actually "sun" individuals in the spring prior to their longer period in the summer shade.

Ginsenoside Rg1 Delays Tert-Butyl Hydroperoxide-Induced Premature Senescence in Human WI-38 Diploid Fibroblast Cells

Tert-butyl hydroperoxide (t-BHP), an analog of hydroperoxide, induced characteristic changes of senescence in human diploid fibroblasts WI-38 cells. It was reported that ginsenoside Rg1, an active ingredient of ginseng, ameliorated learning deficits in aged rats. The present study was aimed to investigate whether ginsenoside Rg1 can delay the premature senescence of WI-38 cells induced by t-BHP and to explore the underlying molecular mechanisms. First, Rg1 pretreatment markedly reversed senescent morphological changes in WI-38 cells induced by t-BHP. Second, t-BHP treatment alone resulted in an increase in the protein levels of P16 and P21, and a decline in intracellular adenosine 5'-triphosphate (ATP) level and mitochondrial complex IV activity. Ginsenoside Rg1 pretreatment had significant effects of attenuating these changes. These data indicate that ginsenoside Rg1 has an anti-aging effect on t-BHP-induced premature senescence in WI-38 cells. This effect may be mediated by regulating cell cycle proteins and enhancing mitochondrial functioning.

Heterologous overexpression of the birch FRUITFULL-like MADS-box gene BpMADS4 prevents normal senescence and winter dormancy in Populus tremula L.

MADS-box genes have been shown to be important to flower and vegetative tissue development, senescence and winter dormancy in many plant species. Heterologous overexpression of known MADS-box genes has also been used for unravelling gene regulation mechanisms in forest tree species. The constitutive expression of the BpMADS4 gene from birch in poplar, known to induce early flowering in birch and apple, induced broad changes in senescence and winter dormancy but no early flowering. Other analyses revealed that 35S::BpMADS4 poplars maintained photosynthetic activity, chlorophyll and proteins in leaves under winter conditions. BpMADS4 may be influencing transcription factors regulating the senescence and dormancy process due to homology with poplar proteins related to both traits. Little is known of the regulatory genes that co-ordinate senescence, dormancy, chlorophyll/protein degradation, and photosynthesis at the molecular level. Dissecting the molecular characteristics of senescence regulation will probably involve the understanding of multiple and novel regulatory pathways. The results presented here open new horizons for the identification of regulatory mechanisms related to dormancy and senescence in poplar and other temperate tree species. They confirm recent reports of common signalling intermediates between flowering time and growth cessation in trees (Böhlenius et al. in Science 312:1040-1043, 2006) and additionally indicate similar connections between flowering time signals and senescence.

Catch-Up Growth after Hypothyroidism Is Caused by Delayed Growth Plate Senescence

Catch-up growth is defined as a linear growth rate greater than expected for age after a period of growth inhibition. We hypothesized that catch-up growth occurs because growth-inhibiting conditions conserve the limited proliferative capacity of growth plate chondrocytes, thus slowing the normal process of growth plate senescence. When the growth-inhibiting condition resolves, the growth plates are less senescent and therefore grow more rapidly than normal for age. To test this hypothesis, we administered propylthiouracil to newborn rats for 8 wk to induce hypothyroidism and then stopped the propylthiouracil to allow catch-up growth. In untreated controls, the growth plates underwent progressive, senescent changes in multiple functional and structural characteristics. We also identified genes that showed large changes in mRNA expression in growth plate and used these changes as molecular markers of senescence. In treated animals, after stopping propylthiouracil, these functional, structural, and molecular senescent changes were delayed, compared with controls. This delayed senescence included a delayed decline in longitudinal growth rate, resulting in catch-up growth. The findings demonstrate that growth inhibition due to hypothyroidism slows the developmental program of growth plate senescence, including the normal decline in the rate of longitudinal bone growth, thus accounting for catch-up growth.

Lack of visible post-pollination effects in pollen grains of two Dendrobium cultivars: relationship with pollinia ACC, pollen germination, and pollen tube growth.

Dendrobium flowers, pollinated with pollinia from individuals of the same cultivar or other cultivars, usually show rapid post-pollination effects such as floral epinasty, a change in flower colour and early perianth senescence. However, pollination with the pollinia of cv. Karen or cv. Kenny flowers did not produce these effects. We compared these two cultivars with cvv. Pompadour, Willie and Sakura, and tested the hypotheses that the differences were related to levels of 1-aminocyclopropane-1-carboxylic acid (ACC) in the pollinia, ethylene production by the pollinated flower, pollen germination, or pollen tube growth. The pollinia of cvv. Karen and Kenny contained as much ACC as the pollinia of cv. Pompadour, but less than the pollinia of cvv. Willie and Sakura. Ethylene production after pollination with cvv. Karen and Kenny pollinia was much lower than after pollination with pollinia from the other cultivars tested. The pollen grains showed normal germination, but cvv. Karen and Kenny pollen grains exhibited much less tube growth than those of the other cultivars. Pollen tube growth in cv. Pompadour was positively affected by ethylene. Ethylene was required and sufficient for the induction of epinasty, rapid perianth colour changes and early perianth senescence, very similar to the changes after pollination. The absence of these effects after pollination with cvv. Kenny and Karen seems to be due to the low ethylene production induced by the pollinia of these cultivars. This low ethylene production could not be accounted for by the ACC content in the pollinia of cvv. Kenny and Karen.

Profiling influences of senescent and aged fibroblasts on prostate carcinogenesis

Experimental evidence suggests that ageing-associated alterations in the tissue microenvironment act to promote prostate carcinogenesis. In this review, we survey the cellular state of senescence, review its causes, and describe associations with ageing and cancer. We further discuss senescent stromal gene expression changes, which may mediate these effects, and that may serve as therapeutic targets.

Time- and Dose-Dependent Effects of Chronic Wound Fluid on Human Adult Dermal Fibroblasts

Wound healing is a biologic process that is altered in patients affected by chronic venous ulcers. The wound microenvironment is reflected in the chronic wound fluid (CWF), an exudate containing serum components and tissue-derived proteins. We investigated the effects of increasing doses of CWF collected from patients suffering from chronic venous ulcers on human adult dermal fibroblasts cultured in vitro and the relationship among CWF effects and treatment length. Fibroblasts were treated with 60, 240, and 720 microg/mL CWF for 3 and 7 days. We evaluated cell proliferation and viability by MTT and Trypan blue assay, cell morphology by light microscopy, F-actin microfilaments organization by tetramethylrhodamine B isothiocyanate-conjugated phalloidin, alpha-smooth muscle actin expression by immunofluorescence, and senescence-associated beta-galactosidase activity. CWF induced an increase in cell proliferation in the first 3 days of treatment. In contrast, at 7 days, a strong decrease in cell viability was observed. These changes were related to a cytoskeletal F-actin reorganization and not to fibroblast-myofibroblast differentiation nor to changes in cellular senescence. This study shows a dose-dependent and biphasic effect of CWF on dermal fibroblasts, suggesting that a continuous exposure to chronic wounds microenvironment may induce late cellular dysfunctions possibly involved in the delayed wound healing.

Are green islands red herrings? Significance of green islands in plant interactions with pathogens and pests

The term green island was first used to describe an area of living, green tissue surrounding a site of infection by an obligately biotrophic fungal pathogen, differentiated from neighbouring yellowing, senescent tissue. However, it has now been used to describe symptoms formed in response to necrotrophic fungal pathogens, virus infection and infestation by certain insects. In leaves infected by obligate biotrophs such as rust and powdery mildew pathogens, green islands are areas where senescence is retarded, photosynthetic activity is maintained and polyamines accumulate. We propose such areas, in which both host and pathogen cells are alive, be termed green bionissia. By contrast, we propose that green areas associated with leaf damage caused by toxins produced by necrotrophic fungal pathogens be termed green necronissia. A range of biotrophic/hemibiotrophic fungi and leaf-mining insects produce cytokinins and it has been suggested that this cytokinin secretion may be responsible for the green island formation. Indeed, localised cytokinin accumulation may be a common mechanism responsible for green island formation in interactions of plants with biotrophic fungi, viruses and insects. Models have been developed to study if green island formation is pathogen-mediated or host-mediated. They suggest that green bionissia on leaves infected by biotrophic fungal pathogens represent zones of host tissue, altered physiologically to allow the pathogen maximum access to nutrients early in the interaction, thus supporting early sporulation and increasing pathogen fitness. They lead to the suggestion that green islands are 'red herrings', representing no more than the consequence of the infection process and discrete changes in leaf senescence.

Acoustic Communication and Sexual Behaviour of Insects

Acoustic communication functions in different taxons of insects are discussed. Peculiarities of Drosophila melanogaster acoustic system are under special interest. Different acoustic signal types are described. Senescence changes in love song and neurophysiology aspects of courtship behavior are examined.

Macrophages feel their age in macular degeneration

Macular degeneration, during which the posterior part of the eye known as the macula suffers from thinning, atrophy, and bleeding caused by abnormal angiogenesis (blood vessel formation), predominantly affects elderly adults and results in the loss of central vision. In this issue of the JCI, Kelly et al. investigate the regulation of innate immune cells, specifically macrophages, in ocular neovascularization following eye injury in mice (see the related article beginning on page 3421). They found that, as the mice aged, increased expression of IL-10 by senescent macrophages and changes in their expression of other cytokines altered the ability of these cells to restrain trauma-induced angiogenesis in the eye. These data provide insight into the effect of senescence on macrophage function and angiogenesis and have important implications for age-related diseases such as macular degeneration.

Mitochondrial Fission and Fusion Mediators, hFis1 and OPA1, Modulate Cellular Senescence

The number and morphology of mitochondria within a cell are precisely regulated by the mitochondrial fission and fusion machinery. The human protein, hFis1, participates in mitochondrial fission by recruiting the Drp1 into the mitochondria. Using short hairpin RNA, we reduced the expression levels of hFis1 in mammalian cells. Cells lacking hFis1 showed sustained elongation of mitochondria and underwent significant cellular morphological changes, including enlargement, flattening, and increased cellular granularity. In these cells, staining for acidic senescence-associated beta-galactosidase activity was elevated, and the rate of cell proliferation was greatly reduced, indicating that cells lacking hFis1 undergo senescence-associated phenotypic changes. Reintroduction of the hFis1 gene into hFis1-depleted cells restored mitochondrial fragmentation and suppressed senescence-associated beta-galactosidase activity. Moreover, depletion of both hFis1 and OPA1, a critical component of mitochondrial fusion, resulted in extensive mitochondrial fragmentation and markedly rescued cells from senescence-associated phenotypic changes. Intriguingly, sustained elongation of mitochondria was associated with decreased mitochondrial membrane potential, increased reactive oxygen species production, and DNA damage. The data indicate that sustained mitochondrial elongation induces senescence-associated phenotypic changes that can be neutralized by mitochondrial fragmentation. Thus, one of the key functions of mitochondrial fission might be prevention of the sustained extensive mitochondrial elongation that triggers cellular senescence.

Differentiation potential of urothelium from patients with benign bladder dysfunction

To develop a novel in vitro approach to test the hypothesis that failure of urothelial differentiation underlies the aetiopathology of interstitial cystitis (IC), where there is evidence of compromised urinary barrier function, as benign dysfunctional bladder disease encompass several poorly understood clinically defined conditions, including IC, idiopathic detrusor overactivity (IDO) and stress urinary incontinence (SUI). Biopsy-derived urothelial cells from dysfunctional bladder biopsies were propagated as finite cell lines and examined for their capacity to differentiate in vitro, as assessed by the acquisition of a transitional cell morphology, a switch from a cytokeratin (CK)13(lo)/CK14(hi) to a CK13(hi)/CK14(lo) phenotype, expression of claudin 3, 4 and 5 proteins, and induction of uroplakin gene transcription. Two of 12 SUI cell lines showed early senescent changes in culture and were not characterized further; one of seven IC, one of five IDO and a further three SUI cell lines had some evidence of senescence at passage 3. Of the seven IC-derived cell lines, four showed a near normal range of differentiation-associated responses, but the remainder showed little or no response. Most IDO cell lines (four of five) showed a normal differentiation response, but at least three of the 10 SUI cell lines showed some compromise of differentiation potential. This study supports the existence of a subset of patients with IC in whom a failure of urothelial cytodifferentiation might contribute to the disease, and provides a novel platform for investigating the cell biology of urothelium from SUI and other benign dysfunctional conditions.