Aging is not Senescence: A Short Computer Demonstration and Implications for Medical Practice

INTRODUCTION: The discussion regarding the evolution of aging is almost as old as Darwinian Evolution Theory, but to date, it has remained one of biology's unresolved problems. One issue is how to reconcile natural selection, which is understood as a process that purges deleterious characteristics, with senescence, which seems to offer no advantages to the individual. METHOD: A computer simulation that illustrates an evolutionary mechanism for the development of senescence in populations is presented. DISCUSSION: In this article, we debate that two popular explanations for the existence of senescence, namely, (1) the removal of elders for the benefit of the species and (2) the progressive deterioration of the organic machine due to continuous use, are not correct. While human populations continue to age, it is important that the physician understands that senescence, here defined as the progressive impairment of an organism, does not necessarily accompany aging, which we here define as the mere passage of time. As such, we argue that certain processes that were originally assumed to be part of aging should have their status changed because they are actually diseases. Physicians often encounter situations that depend on a better understanding of what limitations senescence imposes on most living species. The concepts of aging (the unavoidable passage of time), senescence (progressive physiologic impairment), and senility (the pathological development of diseases), are discussed

Signal transduction in the Sertoli cell: serum modulation of the response to FSH

Immature Sertoli cells of the testicular seminiferous tubule maintain the expression of their differentiated phenotype when cultured in unsupplemented medium. In preliminary experiments we observed that foetal bovine serum (FBS) stimulates polyphosphoinositides (PI) hydrolysis in Sertoli cells. We then evaluated the effect of serum on the function of the immature Sertoli cell in culture, in terms of cAMP and estrogen production. Treatment of Sertoli cells for 30 min with 1–10% FBS had no effect on basal cAMP accumulation but abolished the response to FSH. The serum concentration producing half-maximal inhibition of the FSH-dependent cAMP accumulation was 0.5–1%. Comparison of the FSH-dose-response in the absence or presence of serum showed a decreased maximal response when serum was present. Sertoli cells exposed to serum were also less responsive to the β-adrenergic agonist isoproterenol, to cholera toxin, and to forskolin. The serum inhibition was rapidly reversed upon removal of serum or incubating the cells with the phosphodiesterase inhibitor MIX (methyl-isobutyl-xanthine). Similarly to what observed with cAMP, serum affected androgen aromatization stimulated by FSH, isoproterenol, cholera toxin, forskolin and dibutyryl cAMP. These data indicate that factors present in serum can act as modulators of the Sertoli cell function in vitro by rapidly and reversibly inhibiting the cAMP and steroidogenic response of the Sertoli cell to FSH

Synthesis and Stereochemical Characterization of a Novel Chiral α-Tetrazole Binaphthylazepine Organocatalyst

A novel α-tetrazole-substituted 1,1'-binaphthylazepine chiral catalyst has been synthesized and its absolute configuration has been determined by DFT computational analysis of the vibrational circular dichroism (VCD) spectrum of its precursor. The VCD analysis, carried out through the model averaging method, allowed to assign the absolute configuration of a benzylic stereocenter in the presence of a chiral binaphthyl moiety. The 1,1'-binaphthylazepine tetrazole and the nitrile its immediate synthetic precursor, have been preliminarily tested as chiral organocatalysts in the asymmetric intramolecular oxa-Michael cyclization of 2-hydroxy chalcones for the synthesis of chiral flavanones obtaining low enantioselectivity

Relationship between actin microfilaments and plasma membrane changes during apoptosis of neoplastic cell lines in different culture conditions

In this study we investigated the relationship between the reorganisation of actin cytoskeleton and the changes at cell surface level (i.e. PS exposure and blebbing) in two neoplastic cell lines during apoptosis: Chang liver cells (adherent culture) and promyelocytic HL-60 cells (suspension culture), treated with the podophyllotoxin derivative VP16. The morphological analysis, performed by means of conventional fluorescence microscopy and confocal laser scanning microscopy, on Chang cells showed that onset and progress of the two processes are synchronised. The initial disassembly of stress fibers was associated with the early PS exposure on the cell surface. Moreover, the accumulation of actin at cortical level appeared strongly associated with an intense labelling for Annexin V and, in some cases, especially in the areas of membrane blebbing. The double staining for actin and PS exposure, quantitatively analysed by flow cytometry in HL-60 cells after different treatment times, demonstrated that the decrease of Annexin V binding in the late stages of apoptosis is associated with the strong reduction of actin labelling probably also due to a proteolytic cleavage. These events were also partially related to variations of 255 the functional state of mitochondria, by analysing cytofluorometrically the dissipation of the inner membrane potential (DYm)

HCV-related nervous system disorders

Chronic infection with hepatitis C virus (HCV) is associated with a wide spectrum of extrahepatic manifestations, affecting different organ systems. Neurological complications occur in a large number of patients and range from peripheral neuropathy to cognitive impairment. Pathogenetic mechanisms responsible for nervous system dysfunction are mainly related to the upregulation of the host immune response with production of autoantibodies, immune complexes, and cryoglobulins. Alternative mechanisms include possible extrahepatic replication of HCV in neural tissues and the effects of circulating inflammatory cytokines and chemokines

Progressive multifocal leukoencephalopathy in a patient with Good's syndrome

Good's syndrome (GS) is an immunodeficiency characterised by thymoma, hypogammaglobulinemia and impaired T-cell function. The clinical symptoms are recurrent or chronic infections from common or opportunistic pathogens and diarrhoea. Encephalitis is rare, mostly associated to cytomegalovirus. We present a 65-year-old woman who developed blindness, motor deficits and cognitive changes over a 4-month period. MRI of the brain showed symmetric subcortical white matter changes in the occipital lobes, first thought to correspond to posterior reversible encephalopathy syndrome. A thymoma was found and operated. The patient had no B cells, low immunoglobulins and an inverted CD4/CD8 ratio. GS was diagnosed. In the cerbrospinal fluid >1  million JC virus copies/mL were found and a repeat MRI now showed a picture compatible with progressive multifocal leucoencephalopathy (PML). Her disease had a fatal outcome. The present case is the second reported association between GS and PML

Erratum to: Prevalence of renal artery stenosis in patients undergoing cardiac catheterization

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