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Notes: The scientific view of aging is still rather fragmented, because no sound unifying aging theory yet exists. Most hypotheses are rather limited, in the sense that they describe only the some aspect of the aging phenomenon, summarized in the aspect theory of aging. But it cannot be denied that the majority of hypotheses are based on a deterministic view of aging. This kind of concept presents a single strategy of aging control wholly dependent on the replacement principle, which purports the substitution of all possible tools, such as genes, cells, tissues and organs. But, recently a novel aging concept has been proposed, based on the possible control of aged cells. Therefore, the new concept of aging and a novel approach for the development of a strategic pathway to aging control are introduced, which may hopefully result in functional longevity.The concept that aging is an irreversible, inevitable, universal process of an organism provides the basis of the deterministic view of aging. The underlying view of aging as a determined irresistible fate has conjured many hypothesis on the aging process such as aging clock hypothesis, genetic determinism, telomere hypothesis, wearing hypothesis, disposable soma hypothesis and error catastrophe hypothesis, etc. Although these hypotheses are under debates, the majority of scientists and the public are inclined to accept these ideas, preoccupied by the view that aging is a natural irresistible process leading to death. Based on the deterministic view on aging, it would be natural to adopt the replacement principle as the ultimate strategy for counteracting the aging process.In other words, if the aging process were irreversible, inevitable, irresistible and universal, only the replacement principle provides a solution, that is, just substitute the aged material with new fresh material. Many replacement principles have been developed at various levels from genes to organs. However, when we examine the replacement principle, many gloomy aspects of its approaches can be identified. At the gene level, the fundamental question of existence of gerontogene has not been resolved, though many virtual gerontogenes have been suggested. In terms of the cell therapy approach, stem cell have recently attracted a great deal of attention, but still the problem of the stem cell niche and the mode of regulating stem cell development have not been unveiled. At the tissue or organ level, tissue patches, artificial organs and the transplantation approach have been elaborately pursued. However, it is well known that these methods are restricted because of our limited knowledge on the complex of coordinated development, bionanotechnology and immuno-compatibility, etc. This reality encourages to depend on camouflage transient strategies such as plastic surgery or hormonal supplementation.The complex nature of aging, denying the consensus explanation of aging, has led us to pursue historic views of aging. The core problem in understanding the aging process is the traditional prejudice concerning aging as a one-way phenomenon based on the deterministic view. However, the aging process has now been revealed to be a reactive phenomenon based on adaptive response and designed to maintain the purpose of an organism, its LIFE. Aging-related complicated changes in metabolism, signal transduction, stress response, cytoskeletal modulation, and in genetic control are adaptive and responsive, as opposed to the deterministic programmed systems, presumed to be operating in the aging process. Therefore, it is natural that large differences in the aging process are observed not only at the individual level but also at the interorgan level in the same individuals.In our previous papers, we have reported that increased levels of caveolin are mainly responsible for the hyporesponsiveness of senescent cells through the modulation of receptor-mediated endocytosis. And we have shown that the senescent phenotype of growth factor response loss can be resumed by simply reducing the caveolin status. Moreover, the adjustment of the caveolin status of old cells restored not only their functional efficiencies by adjusting the signal transduction apparatus but also their structural features, probably by modulating focal adhesion complex activities.Therefore, it can be tentatively concluded that the fundamental notion of aging as a process of functional deterioration and morphological alteration are affected by caveolin status. Such data suggest that caveolin plays the role of gatekeeper in the aging process, for if increased, aging results, but if decreased, the senescent phenotype disappears. In addition to caveolins, there seem to be several other tentative gatekeeper molecules, such as amphiphysin and some G proteins.If the existence of a molecular gatekeeper for aging were assumed, it would be natural to suppose that an aging field could be generated inside a cell, as regulated by the gatekeeper. This novel concept would explain the aging phenotype as an adaptive responsive phenomenon toward environmental stress. Since caveolin is one of the candidate gatekeepers, its simple increase or decrease might be responsible for many aspects of the aging phenotype. Therefore, we suggest that the aging phenotype can be explained in terms of a new aging hypothesis, namely the gate theory of aging. The characteristic features of this novel view of aging are its focus upon flexibility rather than irreversibility, manageability rather than inevitability, and individuality rather than generality.The gate theory of aging implies the possibility of adjusting the aging phenotype. Based on this theory, the restoration principle can be proposed as a novel approach to aging control. For example, the effect of nutrition and exercise, which result in changes in cellular cholesterol content and promoter methylation status, would profoundly influence the cellular caveolin status. Therefore, it can be presumed that the aging phenotype can be adjusted to induce restoration by modulating gatekeeper molecules, illustrated by caveolin. There may be many other tools, which can be used to augment the actions of aging-related gatekeepers.As society enters a new era of longevity, never before experienced problems concerning the elderly are generated at the social, economic, environmental, medical and cultural levels. However, most problems are based on the traditional concept of aging; that is the deterministic view on aging as an irreversible, inevitable, inefficient status. But, now it is clear that the aging process can be explained in a totally different way, as an adaptive response to age, which implies the possibility of restoration by adjusting the cellular apparatus. Actually, this new aspect of aging is readily illustrated by the superlongevity of people like centenarians. There are now many centenarians in good shape with a good status, and sound social skills.The active attitude and the positive way of life shown by centenarians present the longlive community with a new concept; functional longevity. The adoption of this approach to life marks revolutionary conversion of the view of aging from simple longevity to functional longevity. The concept of functional longevity incorporates active participation, positive thinking, and responsible behavior. It may be concluded that the concept of functional longevity based on the gate theory of aging may be used to solve the emerging problems associated with aging and aged societies.〈section xml:id="abs1-1"〉〈title type="main"〉References 1. Cho, K.A., Ryu, S.J., Oh, Y.S., Park, J.H., Lee, J.W., Kim, K.T., Jang, I.S. and Park, S.C. Morphological adjustment of senescent cells by modulating caveolin-1 status. J. Biol. Chem. (2004) (epublication ahead of print).2. Cho, K.A., Ryu, S.J., Park, J.S., Jang, I.S., Ahn, J.S., Kim, K.T. and Park, S.C. Senescent phenotype can be reversed by reduction of caveolin status. J. Biol. Chem.278, 27789–27795 (2

Notes: A human Cu,Zn-superoxide dismutase was fused with a transcriptional transactivator protein transduction domain of HIV-1 to produce a novel anti-aging ingredient for cosmeceuticals, transcriptional transactivator superoxide dismutase (Tat-SOD). Stability tests and evaluation of the transduction efficacy and enzymatic activity suggest Tat-SOD is an effective active ingredient for anti-aging treatment.

Notes: 1 This study evaluated the inhibitory action of apigenin-7-O-β-d-glucuronopyranoside (AGC), apigenin, and omeprazole on reflux oesophagitis and gastritis in rats. AGC was isolated from Clerodendron trichotomum leaves. 2 Oesophagitis and gastritis were induced by surgical procedure and the administration of indomethacin, respectively. The intraduodenal (i.d.) administration of AGC decreased the volume of gastric juice and increased the gastric pH compared with apigenin and omeprazole. The acid output was more inhibited by AGC in a dose-dependent manner than by apigenin and omeprazole. Compared with apigenin and omeprazole, AGC significantly decreased the size of gastric lesions, which were induced by exposure of the gastric mucosa to indomethacin. 3 Malondialdehyde (MDA) content, which is the end product of lipid peroxidation, was increased significantly after the induction of reflux oesophagitis. The MDA content was decreased by AGC (i.d. 3 mg kg−1), but not by either apigenin or omeprazole. This suggests that AGC has an antioxidative effect. In the oesophagitis group, the mucosal levels of glutathione (GSH) were significantly lower than that in the normal group. However, the GSH levels were preserved after administering the AGC, suggesting that AGC possesses scavenging activity. 4 In summary, AGC is more potent than apigenin and omeprazole at inhibiting reflux oesophagitis and gastritis and may therefore be a promising drug for their treatment.

Notes: Aims : To evaluate the caveolin-1 status of invasive ductal carcinoma and its correlation with other important parameters of breast carcinogenesis. Caveolin-1, the main structural protein of caveolae, is involved in the regulation of several intracellular signalling pathways and also functions as a tumour suppressor in breast carcinogenesis.Methods and results : One hundred and thirty cases of invasive ductal carcinomas with matched normal breast tissue were evaluated immunohistochemically for caveolin-1 expression. Using a tissue microarray, caveolin-1 expression was also correlated with the expression of other antigens such as eostrogen receptor, progesterone receptor, epidermal growth factor receptor (EGFR), HER2, β-catenin, E-cadherin, p53, Ki67 and with clinicopathological parameters. Immunohistochemical results showed strong expression of caveolin-1 in all normal breast epithelial cells, but a reduction of caveolin-1 expression in 56 cases (43.1%) of invasive ductal carcinoma. Furthermore, a statistically significant inverse correlation between caveolin-1 and EGFR and HER2 was noted (P 〈 0.001).Conclusions : Our results indicate a reduction in caveolin-1 expression in invasive ductal carcinoma of the breast, which supports in vitro studies of its role as a tumour suppressor. Caveolin-1 also shows an inverse correlation with EGFR and HER2, which fits with its function as a negative regulator of signal transduction.

Notes: Aims : To evaluate the different expression patterns and the prognostic significance of cell cycle regulatory molecules in diffuse large B-cell lymphomas (DLBCLs) of germinal centre (GC) and non-GC phenotypes.Methods and results : Tissue microarray slides composed of 126 extranodal and 88 nodal DLBCLs were immunostained for p16, p21, p27, p14 and p53. DLBCLs were classified into GC and non-GC phenotype according to the immunohistochemical expression of bcl-6, CD10, and MUM1. Aberrant expression of p53 was more frequent in the GC phenotype in nodal cases (P = 0.038), and the loss of p16, p21 and p14 expression was significantly more common in the non-GC phenotype (P = 0.004, P = 0.001, P 〈 0.001). Concurrent disruptions of the p16-Rb and p14-p53 pathways as represented by the immunoprofile of p16/p14/p53 (–/–/+) were associated with a poor prognosis in the GC phenotype [mean survival 31 months in the p16/p14/p53 (–/–/+) group versus 62 months in the other groups, P =0.0485].Conclusions : The expression and prognostic implications of cell cycle regulatory molecules differ between GC and non-GC phenotypes in DLBCLs. The immunoprofile of p16/p14/p53 (–/–/+) within the GC phenotype of DLBCLs can be defined as a poor prognostic subgroup.

Notes: Summary.  Haemophilia A is an X-linked inherited bleeding disorder. Linkage diagnosis using polymorphic markers in the factor VIII gene is used to archive the carrier detection and prenatal diagnosis. The objective of this study was to establish the allele frequency and heterozygosity rate (HR) of two new intragenic markers (Intron 1 and 24) and other markers (Intron 13 and 22) using fluorescent PCR. Five hundred unrelated healthy women were screened and haemophilic family was studied for carrier detection and prenatal diagnosis. We observed five different alleles of Intron 1, 10 of Intron 24, nine of Intron 13 and six of Intron 22. The observed HR for Intron 1, 24, 13 and 22 were 34.0, 35.2, 53.0 and 42.6%, while the expected HR were 33.6, 36.3, 50.1 and 44.3%, respectively. Heterozygosity rate with the combined use of all four intragenic markers was 76.6% (383/500). In prenatal diagnosis of a haemophilic family, a pregnant woman was heterozygous with three intragenic (Intron 1, 13 and 22) and one extragenic St14 VNTR (DXS52) markers. She was considered to be a carrier, and she carried a male foetus by AMXY PCR and chromosome analysis of amniocytes. Foetus did not have mutant haplotype as his uncle, suggesting a normal male status. Our study demonstrates the utility of two new intragenic markers in FVIII gene for carrier detection and prenatal diagnosis of haemophilic families.

Notes: The present contribution reports the unlubricated friction and wear properties of Ti3SiC2 against steel. The fretting experiments were performed under varying load (1–10 N) and the detailed wear mechanism is studied using SEM-EDS, Raman spectroscopy, and atomic force microscopy. Under the selected fretting conditions, Ti3SiC2/steel tribocouple exhibits a transition in friction as well as wear behavior with coefficient of friction varying between 0.5 and 0.6 and wear rate in the order of 10−5 mm3·(N·m)−1. Raman analysis reveals that the fretting wear is accompanied by the triboxidation with the formation of TiO2, SiO2, and Fe2O3. A plausible explanation for the transition in friction and wear with load is proposed.

Notes: Chromoblastomycosis is a cutaneous and subcutaneous mycotic disease caused by the dematiaceous (black) fungi. Five species of fungi are known generally to be the cause: Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporium carrionii, F. compacta and Rhinocladiella cerphilum. In infected tissue they can appear as pigmented sclerotic bodies, commonly called ‘copper pennies’, which are pathognomonic of chromoblastomycosis. The infection usually occurs through traumatic skin inoculation, with the majority of lesions occurring on the feet and legs of outdoor workers. We report a patient in whom the lesions had begun on the right breast, which is an unexposed area, without a history of trauma. A uniform, reliable treatment does not exist but our patient was mycologically cured with the use of amphotericin B and the subsequent combination of 5-flucytosine and itraconazole.

Notes: The inhibitory activity of water extracts from the shoots and roots of three rice cultivars, Taichung native 1 (TN1) and IAC165 (both allelopathic rice) and AUS196 (non-allelopathic rice), grown in hydroponics was evaluated. The release of germination inhibitors by allelopathic rice plants into hydroponic solution was also determined with freshly collected solution and XAD-4 resin desorbate. The degree of the inhibition was quantified in terms of root growth in Echinochloa colona, Echinochloa crus-galli, Echinochloa crus-galli var. oryzicola, Triantema portulacastrum and Lactuca sativa. The allelopathic activity of rice was species specific, and depended on source and concentration. Root length of all test species was inhibited by the different concentrations of shoot extract of allelopathic and non-allelopathic rice. However, of the three cultivars, TN1 showed higher inhibition than IAC165 and AUS196 in all test species. Water extracts of shoots and roots significantly inhibited root growth in E. crus-galli but the shoot extract gave a greater inhibitory effect on E. crus-galli than the root extract. Root exudate of TN1 inhibited root elongation of E. crus-galli from 2 weeks after transplanting (WAT) and the inhibition continued for 4 WAT. The results confirmed the previous finding of a laboratory bioassay that the TN1 had allelopathic activity and produced allelochemicals that inhibit growth of some weed species.

Notes: This study was carried out to investigate the motor neurone degeneration in the ventral horn following transient spinal cord ischaemia at normothermic conditions in rabbits. Transient spinal cord ischaemia was induced by occlusion of the abdominal aorta underneath the left renal artery for 15 min at normothermia (38.7°C). Sections at the level of L7 were examined using histochemical and electron microscopic methods. Cresyl violet-positive motor neurones began to reduce in number at 3 h after ischaemia reperfusion, and were not detectable at 48 h after ischaemia reperfusion. Acid fuchsin-positive motor neurones were detected at 1 h after ischaemia reperfusion, significantly increased up to 6 h after the ischaemia reperfusion, and eventually disappeared by 48 h after ischaemia reperfusion. In electron microscopic findings, the disintegration of cytoplasmic membranes, and the disruption of mitochondria and endoplasmic reticulum were observed in motor neurones at 30 min after ischaemia reperfusion. Motor neurones showed necrotic findings with pyknotic degeneration at 1 h after ischaemia reperfusion. The necrotic degeneration became severer time dependently after ischaemia reperfusion. At 48 h after ischaemia reperfusion, cellular components were not detectable in motor neurones. In conclusion, we suggest that the degeneration pattern of motor neurones of the ischaemic spinal cord was necrotic after ischaemia reperfusion under normothermic conditions.