Current Aging Science (v.4, #1)

The Effect of Resveratrol on the Werner Syndrome RecQ Helicase Gene and Telomerase Activity by Fumiaki Uchiumi, Takeshi Watanabe, Shin Hasegawa, Taisuke Hoshi, Yoshikazu Higami, Sei-ichi Tanuma (1-7).
Various protein factors, including telomerase and WRN helicase, are involved in telomere maintenance. Resveratrol (Rsv), a polyphenol that extends the lifespan of diverse species is an activator of SIRT1, a NAD+ dependent deacetylating enzyme in mammalian cells. Here, we examined the changes in gene expressions and promoter activities of WRN helicase and telomerase after Rsv treatment. This treatment increased the amount of WRN transcript and protein product by activating its promoter and telomerase promoter activity and gene expression. However cell proliferation was not changed. This suggests that Rsv induces telomere maintenance factors like WRN helicase without affecting cell proliferation.

Proteins are susceptible to numerous non-enzymatic post-translational modifications which occur both during normal aging and in neurodegenerative states. For instance, formation of abnormal L-isoaspartyl residues arising from both the deamidation of L-asparaginyl residues and the isomerization of L-aspartyl residues is a frequent chemical modification that affects proteins. The formation of L- isoaspartyl residues in proteins alters their three-dimensional structure leading usually to a loss of function. Notably, accumulation of isomerized proteins could contribute to metabolic dysfunctions in neuronal cells during aging reducing cognitive functions in elderly patients and would eventually promote the development of neurodegenerative diseases. The protein L-isoaspartyl (D-aspartyl) methyltransferase (PIMT) is an enzyme that recognizes and repairs the abnormal L-isoaspartyl residues in proteins. Its expression appears to decline during aging which could partially explain the build up of damaged proteins in old age. In this review, we summarize recent findings, based mostly on proteomic data, regarding the formation and accumulation of proteins bearing atypical L-isoaspartyl residues as well as PIMT functions during normal aging and in some neurodegenerative diseases. The emphasis is on possible molecular mechanisms controlling PIMT expression and the ability of PIMT to repair isomerized substrates during aging. Investigation of processes regulating age-related accumulation of isomerized proteins is a promising avenue to a better understanding of aging at the protein level.

Influence of Aging on the Dopaminergic Neurons in the Substantia Nigra Pars Compacta of Rats by Jin Gao, Hui Miao, Cheng-hua Xiao, Yu Sun, Xia Du, Hong-hua Yuan, Hong-li Yu, Dian-shuai Gao (19-24).
To study the relationship between aging and the vulnerability of substantia nigra pars compacta (SNc) tyrosine hydroxylase immunoreactive positive (TH+) dopaminergic (DA) neurons. We determined the number of TH+ DA neurons in aged rats (24 mon) compared to adult rats (5 mon) using immunohistochemistry and cell counting. Furthermore, the expression of TH mRNA and protein levels in SN was studied by semi-quantitative RT-PCR and Western blotting. A 13.6and#x25; loss of neurons was detected in rostral segment of SNc, and the expression of TH mRNA levels was also reduced (P andlt; 0.05), however, no difference was detected in TH protein levels (P > 0.05). These data suggest that expression of TH protein may increase in the existing SNc DA neurons, which may compensate for the partial loss of TH+ DA neurons.

Adult adipose mice, high fat diet-fed (HFD) mice, anterior hypothalamus-lesioned obese mice and genetically obese mice, were injected daily with thyrotropin releasing hormone (TRH). The treatment provoked a mobilization of triglycerides in the peripheral blood, a decrease of leptin and a loss of body weight. The weight loss did not depend on TSH-mediated stimulation of thyroid hormone secretion with consequent metabolic hyperthyroidism. The levels of blood cholesterol were not affected or even suppressed. Even at a very high dosage TRH did not affect the obesity of genetically obese mice. The ubiquitous tripeptide TRH may thus constitute a key element in the hormone-controlled regulation of body weight and fat stores in the adult and aging body.

Purpose: HIV-related immunological and multisystem accelerated aging contributes to the premature occurrence of agerelated comorbidities. Such non-AIDS-defining comorbidities include cardiovascular disease, dyslipidemia, osteoporosis and frailty, and are of increasing importance with improved survival on antiretrovirals. This review will describe the underlying pathogenesis of HIVrelated accelerated aging and will thereafter focus on frailty, a clinical concept which has only recently been studied in the HIV field. Methods: A literature search was performed using PubMed. Cited articles were peer reviewed and included prospective, retrospective and basic science studies, systematic reviews and Centers for Disease Control and Prevention data. Results: HIV infection is characterized by profound immune dysregulation, which can hasten cardiovascular, renal, cerebrovascular and bone disease and precede their overt manifestation by years. Viral mediated atherogenesis further accelerates end organ dysfunction and increases mortality. Frailty, a clinical syndrome characterized by multisystem dysregulation and increased vulnerability to stressors, occurs prematurely in HIV-infected persons especially those with advanced disease. Frailty prevalence and clinical characteristics are similar in affected older adults and HIV-infected persons. Its presence is associated with a number of negative outcomes including greater comorbidity and hospitalzation. Conclusion: Premature frailty, like other non-AIDS-defining comorbidities, is a manifestation of HIV-related accelerated aging. The synergism of HIV infection and aging has alarming clinical and socioeconomic implications. Research is needed to identify the factors that predict the development of premature frailty among HIV-infected persons and the optimal prevention and management strategies.

A High Accumulation of Hair Minerals in Mongolian People: 2nd Report; Influence of Manganese, Iron, Lead, Cadmium and Aluminum to Oxidative Stress, Parkinsonism and Arthritis by Fumio Komatsu, Yasuo Kagawa, Terue Kawabata, Yoshinori Kaneko, Ulziiburen Chimedregzen, Baatar Purvee, Jugder Otgon (42-56).
It was previously reported that the hair of Mongolian people showed very high accumulation of manganese (Mn), which may increase oxidative stress. This study (2nd report), indicated that not only Mn but other minerals had also accumulated at high levels in hair. It describes the influence of these minerals on oxidative stress, Parkinson's disease-like symptom (Parkinsonism) and arthritis, these diseases being prevalent in Mongolia. Methods: 299 subjects were enrolled (including 21; Parkinsonism and 25; arthritis) from Ulaanbaatar and 5 other areas in Mongolia. Oxidative stress was evaluated by measuring the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). The minerals accumulated in scalp hair were measured by the inductively coupled plasma mass spectrometry method. As a control, 81 healthy Japanese subjects were enrolled. Results: Mongolian subjects showed high accumulated levels of Mn, iron, lead, cadmium and aluminum accumulations in hair, as compared with Japanese subjects. These levels were correlated with urinary 8-OHdG levels. The subjects with Parkinsonism and arthritis demonstrated higher levels in these minerals than healthy subjects. Conclusion: High accumulations of these minerals may increase oxidative stress in Mongolian people, and induce Parkinsonism and arthritis through the high oxidative stress. The high accumulations of these minerals may be induced by eating large amounts of sheep meat. In addition, sandy wind pollution may also contribute to it.

Ex Vivo Proton NMR Analysis and Characterization of Thymus Lipid Metabolites and their Variation with Age in C57BL/6 Mice by Iago Pinal-Fernandez, Manuel Martin-Pastor, Pedro Ferro-Gallego, Lourdes Dominguez-Gerpe (57-69).
Application 1H NMR spectroscopy techniques to the ex vivo study of thymus of 0.5-24 month-old C57BL/6 mice allowed the identification, the quantification and the estimation of some structural parameters (length and unsaturation) of various lipids in the thymus and their changes with age. An initial decrease of lipid metabolites in the thymus from 0.5 to 1 month of age was followed by large raises on further ageing, with 14, 8, and 4 fold increases for the total lipid content, fatty acids and glycerides, respectively, which correlated positively with age and negatively with thymus involution. The estimated average number of methylene groups per lipid chain essentially doubled its value from approximately 4-5 for the youngest mice to around 8 for the elderly, while the values obtained for the average number of double bonds per chain decreased with age from about 1-0.9 at 0.5/1 months of age to 0.6-0.7 for 18/24 months-old mice. The combination of NMR and histological data allowed studying the age-associated changes of the contribution of adipose- derived lipids to the total lipid content of the thymus and the amount of adipose tissue infiltrating the thymus. Both parameters initially showed a decrease from 0.5 months of age to (the adipose-free thymus at) 1 month of age. Afterwards, a continuous increase was observed on ageing: at 2 months about 55and#x25; of the lipids in the thymus were adipose-derived, while at 24 months they amounted to as much as about 95and#x25; of the total lipid content; for the same age-period, the estimated minimum adipose lipid content in the thymus changed from about 0.26and#x25; to 4.5and#x25;.

Decline of Executive Processes Affects the Identification of Emotional Facial Expressions in Aging by Beatriz Garcia-Rodriguez, Anna Fusari, Sara Fernandez-Guinea, Ana Frank, Jose Antonio Molina, Heiner Ellgring (70-75).
The current study examined the hypothesis that old people have a selective deficit in the identification of emotional facial expressions (EFEs) when the task conditions require the mechanism of the central executive. We have used a Dual Task (DT) paradigm to assess the role of visuo-spatial interference of working memory when processing emotional faces under two conditions: DT at encoding and DT at retrieval. Previous studies have revealed a loss of the ability to identify specific emotional facial expressions (EFEs) in old age. This has been consistently associated with a decline of the ability to coordinate the performance of two tasks concurrently. Working memory is usually tested using DT paradigms. Regarding to aging, there is evidence that with DT performance during encoding the costs are substantial. In contrast, the introduction of a secondary task after the primary task (i.e. at retrieval), had less detrimental effects on primary task performance in either younger or older adults. Our results demonstrate that aging is associated with higher DT costs when EFEs are identified concurrently with a visuo-spatial task. In contrast, there was not a significant age-related decline when the two tasks were presented sequentially. This suggests a deficit of the central executive rather than visuo-spatial memory deficits. The current data provide further support for the hypothesis that emotional processing is and#x201C;top-downand#x201D; controlled, and suggest that the deficits in emotional processing of old people depend, above all, on specific cognitive impairment.

Acknowledgment to the Reviewers by Bentham Science Publishers (76-77).
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