Current Aging Science (v.3, #3)
Pin1: A New Genetic Link between Alzheimer's Disease, Cancer and Aging by Jane A. Driver, Kun Ping Lu (158-165).
Epidemiologic data suggest that people who develop neurodegenerative diseases of aging have a decreased risk of cancer. This is intriguing, since there is growing evidence that neurodegeneration and carcinogenesis share a number of biological pathways, such as abnormal entry into the cell cycle. The unique enzyme Pin1 plays a key role in the pathogenesis of Alzheimer's disease and many human cancers. Pin1 acts on proteins after they have been phosphorylated at specific sites, causing them to twist between two completely distinct conformations. This conformational change profoundly affects protein activity and is a major method of cellular signaling and regulation. In the neuron, Pin1 promotes cellular health by restoring phosphorylated tau and amyloid precursor protein to a functional state. The loss of active Pin1 leads to the accumulation of abnormal tau and the overproduction of and#946;-amyloid, the cardinal features of Alzheimer's disease. Pin1 also regulates the cell cycle and is a necessary enzyme for cell division. Over-expression of Pin1 can promote oncogenesis through a number of signaling pathways. We hypothesize that Pin1 might help explain an inverse relationship between Alzheimer's disease and cancer. Pin1 deficiency in mice leads to an early-aging phenotype, suggesting that Pin1 activity is necessary for healthy aging and the prevention of age-related diseases. We review the role of Pin1 in cancer and neurodegeneration, discuss the relationship between Pin1 and aging, and explore its potential as a diagnostic and therapeutic target.
Younger for Longer: Insulin Signalling, Immunity and Ageing by Francis R.G. Amrit, Robin C. May (166-176).
Genes, the environment and stochastic factors such as lifestyle are major contributors to the universally shared phenomenon of ageing. It is now clear that these different inputs act through evolutionarily conserved pathways to regulate lifespan in a wide range of animals. Among several such pathways, the IIS [Insulin/IGF (Insulin - like growth factor)- like signalling] pathway, initially identified in the roundworm, Caenorhabditis elegans, is the most significant modulator of ageing. Consisting of a PI 3 kinase-signalling cascade downstream of a transmembrane insulin-like growth factor receptor, this pathway ultimately regulates the activity of a transcription factor with a huge repertoire of transcriptional outputs. The effect of this is that the IIS pathway co-ordinately controls several processes, including immunity and stress resistance, which in tandem seem to regulate longevity. Since both the function and molecular architecture of the IIS pathway is conserved from yeast to mammals, this coordinate regulation appears to be a general feature of the ageing processes in animals. Here we review the evolutionary conservation of the IIS pathway and discuss this in relation to recent findings on the molecular basis of ageing. We also reflect on the impact and significance of the evolutionary diversification of this pathway and propose a model for how such differences could explain both inter and intra-species differences in ageing.
Potentiality of Oxygen-Ozonetherapy to Improve the Health of Aging People by Velio Bocci, Iacopo Zanardi, Valter Travagli (177-187).
During the last century the lifespan of human beings has increased from about 49 to almost 80 years owing to the great advances of biomedical sciences. This fact has strongly stimulated the idea that it may be possible to prolong productive life for another twenty years but paradoxically the problem of both hyper- and hyponutrition severely jeopardizes this objective all over the world. Many causes of premature aging have been discussed in order to prevent it or find suitable medical treatment. So far only a moderate restriction of caloric intake that does not alter essential nutrients has proved capable of keeping animals and humans healthier for a prolonged time. This modality appears to activate critical longevity genes that can prolong survival: although this is a valuable line of research it will take considerable time to produce valid drugs to selectively activate these relevant genes. Meantime we propose to evaluate an easy and wellaccepted treatment based on a weekly quasi-total body exposure to oxygen-ozone inside a thermostatically controlled cabinet. The rational exposure to a minimal amount of ozone acting as a mild stressor induces a striking improvement of crucial metabolic activities capable of preserving a good health for several years.
The Relationship between Age-Related Kidney Dysfunction and Framingham Risk Score in Healthy People in China by Xiaojuan Bai, Lulu Han, Jing Liu, Weiguang Zhang, Hongyu Zhou, Shaochen Dong, Ying Sun, Xiangmei Chen (188-197).
Background: Aging process reduces kidney function, glomerular filtration rate (GFR) and/or creatinine clearance rate (Ccr), and also significantly increases the risk level for cardiovascular diseases. The classical Framingham risk equation provides a method for predicting cardiovascular risk, but it does not include the kidney function indexes. In this study, we investigated the relationship between age-related kidney function and Framingham risk score (FRS) in healthy Chinese people, and validated to assess the risk factor by GFR/Ccr. Methods: This community-based cross-sectional study recruited 505 healthy subjects (age from 35 to 93 yr.) with both genders is during September 2007 to June 2008 in Shenyang. Framingham risk equation was used to evaluate cardiovascular risk factors and generate FRS. GFR and Ccr were calculated with Cockcroft-Gault (CG) equation (GFRCG), abbreviated Modification of Diet in Renal Disease Study (MDRD) equation (GFRMDRD1) and modified MDRD equation (GFRMDRD2). All data were sorted according to FRS (low, moderate and high) risk levels, and five different age groups (and#x2264;44 yr; 45-54 yr; 55-64 yr; 65-74 yr and and#x2265;75 yr). The ANOVA, correlation, partial correlation between GFR/Ccr and FRS, as well as other risk factors were analyzed with SPSS16.0 statistical package. Results: As the FRS level increased, GFRCG, GFRMDRD1, GFRMDRD2 and Ccr decreased about 10 to 30and#x25; (low > moderate > high risk group, p andlt; 0.01). While the subjects were getting older, GFRCG, GFRMDRD1, GFRMDRD2 and Ccr showed significant reduction (P andlt; 0.001). Ccr decreased about 50and#x25; from the young to oldest group (p andlt; 0.001). There was a significantly inverse correlation between FRS and GFR with Ccr having the Pearson correlation coefficient -0.586 (GFRCG, P andlt; 0.001), - 0.449 (GFRMDRD1 and GFRMDRD2, P andlt; 0.001), -0.459 (Ccr, P andlt; 0.001). However, the relationship between FRS and Ccr was lost after controlling for age and other confounding variables. Conclusion: In healthy population, we found inverse correlations between Framingham risk score and GFR, Ccr and GFR were independently related to the FRS with similar correlation coefficient among three equations. With the increase of FRS, the GFR and Ccr decrease. Aging is the major factor of GFR and Ccr reduction in the healthy population. We suggest that GFR/Ccr could be used as risk indexes for cardiovascular diseases.
Aging in Bacteria, Immortality or Not-A Critical Review by Jose M.G. Gomez (198-218).
Bacteria were traditionally thought to have a symmetrical binary fission without a clear distinction between soma and germ-line, being thus considered as immortal biological entities. Yet it has been recently described that bacteria also undergo replicative aging (RA). That is, they exhibit finite replicative abilities under good conditions to growth. The apparently initial indistinguishability of sibling cells after cytokinesis is broken. After division, the daughter cell that inherits the and#x201C;oldand#x201D; pole present in the and#x201C;mother celland#x201D; progressively exhibits a decline in its proliferative capacity with increasing cell pole age. This is a clear hallmark and phenotypic manifestation of a bona fide RA phenomenon in toto. While the exact molecular mechanism(s) underlying to this lost of replicative potential are not yet fully understood, the and#x201C;old pole celland#x201D; is considered as an aging parent that in a repeatedly manner is able to produce rejuvenated offspring which inherit a resetting of the biological clock. On the order hand, bacteria exhibit in addition to this and#x201C;mandatoryand#x201D; RA the dubbed conditional senescence (CS). CS is defined as a decline in cellular viability observed in arrested-growing bacteria populations, a phenomenon apparently not related to RA under growing active conditions. To understand bacterial aging, it is necessary to put it within the socialitymulticellularity framework. This is a new conceptual paradigm that expresses the natural reality of the bacterial world. From this more ecological perspective these bacterial aging phenomena probably should represent an insurance/bethedging anticipative survival strategy. This is underpinned in a self-generation of an appropriate level of populational phenotypic diversity. That is, bacterial aging could be considered a communitarian adaptive response to cope with different environmental stresses and threats. I have highlighted the necessity to construct an integrative conceptual framework to achieve a unified view of bacteria aging to answer this fundamental question: what are the reasons of bacterial aging?
Clearance of Amyloid-β Peptide Across the Choroid Plexus in Alzheimer's Disease by Ximena Alvira-Botero, Eva M. Carro (219-229).
Aging and several neurodegenerative diseases bring about changes in the anatomy and physiology of the choroid plexus. The identification of specific membrane receptors that bind and internalize extracellular ligands has revolutionized the traditional roles of this tissue. Amyloid beta peptide (Aand#946;), the major constituent of the amyloid core of senile plaques in patients with Alzheimer's disease (AD) is known to contribute to disease neuropathology and progression. Recent emphasis on comorbidity of AD and a deficient clearance of Aand#946; across the blood brain barrier and bloodcerebrospinal fluid barrier have highlighted the importance of brain Aand#946; clearance in AD. The megalin receptor has also been implicated in the pathogenesis of AD. Faulty Aand#946; clearance from the brain across the choroid plexus epithelium by megalin appears to mediate focal Aand#946; accumulation in AD. Patients with AD have reduced levels of megalin at the choroid plexus, which in turn seem to increase brain levels of Aand#946; through a decreased efflux of brain Aand#946;. Therapies that increase megalin expression at the choroid plexus could potentially control accumulation of brain Aand#946;. This review covers in depth the anatomy and function of the choroid plexus, focusing on the brain barrier at the choroid plexus, as it actively participates in Aand#946; clearance. In addition, we describe the role of the choroid plexus in brain functions, aging and AD, as well as the role of megalin in the process of Aand#946; clearance. Finally, we present current data on the use of choroid plexus cells to repair the damaged brain.
Amyloid Beta (Aβ) Protein- and Amyloid Precursor Protein (APP)- Immunoreactive Structures in the Brains of Aged Tree Shrews by Akiko Yamashita, Eberhard Fuchs, Masato Taira, Motoharu Hayashi (230-238).
Background: Amyloid beta (Aand#946;) accumulates in the human brain in an age-dependent manner during normal aging. However, Aand#946; accumulation has not been observed in rodents during normal aging. Tree shrews, the experimental animals studied here, are as small as rats but have a longer life span than rodents. Methods: We investigated Aand#946; accumulations in the brains of young and aged tree shrews by amyloid histochemistry and immunohistochemistry using antibodies to Aand#946;-42, Aand#946;-40, Aand#946;-16 and amyloid precursor protein (APP). Results: In the brain of young tree shrews, there were no Aand#946;- immunoreactive (-ir) and APP-ir profiles. In the brains of aged tree shrews, Aand#946;-42-ir neuronal profiles were observed in the cortex, subiculum, basal ganglia, mammillary body and hypothalamus, but there were only a few weak Congo red-positive amyloid deposits. Aand#946;-42-, Aand#946;-40-, Aand#946;-16- and APP-ir blood vessels were observed. Conclusions: An early stage of amyloid accumulation occurs in the brains of aged tree shrews, indicating that this animal may be a good model for studying the start of Aand#946; accumulation.
Honey, Health and Longevity by Rose A. Cooper, Ann M. Fehily, Janet E. Pickering, Jorge D. Erusalimsky, Peter C. Elwood (239-241).
Honey is a broad spectrum antimicrobial agent which can enhance wound healing. A beneficial effect in cancer has been shown in cell cultures and in animal studies and a number of further nutritional and physiological effects of relevance to health and function have been shown for honey. A representative sub-sample of 665 men within the Caerphilly Cohort kept a weighed dietary record for seven days. Risk factors for vascular and other diseases in 41 men who recorded eating honey suggest that these men were on the whole healthier than the 624 men who had not recorded honey consumption. All-cause mortality during 25 years of follow-up was considerably lower in the men who had consumed honey, the hazard ratio, adjusted for a number of possible confounding factors, being 0.44 (95and#x25; confidence limits 0.23, 0.86; P andlt; 0.017). Because of the small number of subjects and of deaths in this study, further data from other large cohorts will be required before any effect upon mortality and other health effects of honey consumption can be adequately evaluated.
Effects of Music Therapy on Psychological Symptoms and Heart Rate Variability in Patients with Dementia. A Pilot Study by Alfredo Raglio, Osmano Oasi, Marta Gianotti, Veronica Manzoni, Silvia Bolis, Maria C. Ubezio, Simona Gentile, Daniele Villani, Marco Stramba-Badiale (242-246).
We assessed the effects of music therapy (MT) on behavioral and psychological symptoms (BPSD) in dementia associated with changes in physiological parameters, as heart rate (HR) and heart rate variability (HRV). Twenty subjects were randomly assigned to MT treatment or standard care; all patients underwent neuropsychological assessment and ECG Holter recordings before and after the 15-week treatment. The treatment included 30 MT sessions. Depression significantly decreased (p=0.021) in the MT group. PNN50 improved in 50and#x25; patients of the MT group, but in none of the control group (p=0.013). MT may improve symptoms of depression and increase HRV in demented patients.