Current Aging Science

Volume 3, 3 Issues, 2010
ISSN: 1874-6098 (Print)
ISSN: 1874-6128 (Online)

Current Aging Science
Volume 2, Number 3, December 2009

Contents


Aging, Mitochondria and Male Reproductive Function Pp. 165-173
Sandra Amaral and João Ramalho-Santos
[Abstract] [Full Text Article]


Aging and Inflammation: Etiological Culprits of Cancer Pp. 174-186
Aamir Ahmad, Sanjeev Banerjee, Zhiwei Wang, Dejuan Kong, Adhip P.N. Majumdar and Fazlul H. Sarkar
[Abstract] [Full Text Article]


Age-Related Changes in P-Glycoprotein Expression in Senescence-Accelerated Mouse Pp. 187-192
Bin Wu, Masaki Ueno, Masayuki Onodera, Takashi Kusaka, Cheng-long Huang, Naohisa Hosomi, Kenji Kanenishi and Haruhiko Sakamoto
[Abstract] [Full Text Article]


Mortality According to a Prior Assessment of Biological Age Pp. 193-199
Christopher J. Bulpitt, Riitta L. Antikainen, Hugh L.J. Markowe and Martin J. Shipley
[Abstract] [Full Text Article]


Comparing Age Effects in Normally and Extremely Highly Educated and Intellectually Engaged 65 - 80 Year-olds: Potential Protection from Deficit Through Educational and Intellectual Activities Across the Lifespan Pp. 200-204
Vera Schumacher and Mike Martin
[Abstract] [Full Text Article]


Pathology Associated Memory Deficits in Swedish Mutant Genome-Based Amyloid Precursor Protein Transgenic Mice Pp. 205-213
Brian J. Hock, Kennon M. Lattal, Laura S. Kulnane, Ted Abel and Bruce T. Lamb
[Abstract] [Full Text Article]


Relationship of Dietary Habits and Obesity to Oxidative Stress in Palauan People: Compared with Japanese and Mongolian People Pp. 214-222
Fumio Komatsu, Yasuo Kagawa, Terue Kawabata, Yoshinori Kaneko and Kiyomi Ishiguro
[Abstract] [Full Text Article]


Translational Pharmacology in Aging Men with Benign Prostatic Hyperplasia: Molecular and Clinical Approaches to Alpha₁-Adrenoceptors Pp. 223-239
Yoshiyuki Kojima, Yasue Kubota, Shoichi Sasaki, Yutaro Hayashi and Kenjiro Kohri
[Abstract] [Full Text Article]


Short- and Long-Term Survival of Nonsurgical Intensive Care Patients and its Relation to Diagnosis, Severity of Disease, Age and Comorbidities Pp. 240-248
Peter A. Kaufmann, Karl H. Smolle and Guenter J. Krejs
[Abstract] [Full Text Article]




Abstracts


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Aging, Mitochondria and Male Reproductive Function
Sandra Amaral and João Ramalho-Santos

The rise in life expectancy over the last century, together with higher maternal and paternal ages and have highlighted the issue of reduced fertility with advancing age. Aging of the male reproductive system is incited by multi-factorial changes at molecular, cellular and regulatory levels, and individual characteristics are highly variable, although strongly influenced by lifestyle and environmental factors. Damage accumulated with age leads to progressive deregulation of the hypothalamic-pituitary-gonadal axis and of local auto/paracrine interactions, thereby inducing changes in target organs such as the testis, penis and prostate. Elderly human males produce less testosterone, have fewer motile sperm and a higher incidence of erectile dysfunction and prostate disorders, all of which contribute to lower fertility. Cellular aging can manifest itself at several levels. Aging cells progressively accumulate “waste” products, resulting in a decreased functionally. Changes to mitochondria are among the most remarkable features observed in aging cells and several theories place mitochondria at the hub of cellular events related to aging, namely in terms of the accumulation of oxidative damage to cells and tissues, a process in which these organelles may play a prominent role, although alternative theories have also emerged. Furthermore, mitochondrial energy metabolism is also crucial for male reproductive function and mitochondria may therefore constitute a common link between aging and fertility loss.


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Aging and Inflammation: Etiological Culprits of Cancer
Aamir Ahmad, Sanjeev Banerjee, Zhiwei Wang, Dejuan Kong, Adhip P.N. Majumdar and Fazlul H. Sarkar

The biochemical phenomenon of aging, as universal as it is, still remains poorly understood. A number of diseases are associated with aging either as a cause or consequence of the aging process. The incidence of human cancers increases exponentially with age and therefore cancer stands out as a disease that is intricately connected to the process of aging. Emerging evidence clearly suggests that there is a symbiotic relationship between aging, inflammation and chronic diseases such as cancer; however, it is not clear whether aging leads to the induction of inflammatory processes thereby resulting in the development and maintenance of chronic diseases or whether inflammation is the causative factor for inducing both aging and chronic diseases such as cancer. Moreover, the development of chronic diseases especially cancer could also lead to the induction of inflammatory processes and may cause premature aging, suggesting that longitudinal research strategies must be employed for dissecting the interrelationships between aging, inflammation and cancer. Here, we have described our current understanding on the importance of inflammation, activation of NF-κB and various cytokines and chemokines in the processes of aging and in the development of chronic diseases especially cancer. We have also reviewed the prevailing theories of aging and provided succinct evidence in support of novel theories such as those involving cancer stem cells, the molecular understanding of which would likely hold a great promise towards unraveling the complex relationships between aging, inflammation and cancer.


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Age-Related Changes in P-Glycoprotein Expression in Senescence-Accelerated Mouse
Bin Wu, Masaki Ueno, Masayuki Onodera, Takashi Kusaka, Cheng-long Huang, Naohisa Hosomi, Kenji Kanenishi and Haruhiko Sakamoto

P-glycoprotein, the gene product of ATP-binding cassette, sub-family B (Abcb1), is a representative efflux transporter of cerebral vessels. It was recently reported that the expressions of P-glycoprotein and Abcb1 gene were increased in hippocampal vessels with blood-brain barrier (BBB) damage in stroke–prone hypertensive rats. SAMP8, senescence-accelerated mice with age-related deficits in memory and learning, are known to show age-related damage of BBB. Accordingly, in this study, we examined the P-glycoprotein expression and the gene expression (Abcb1α/b) by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical techniques. SAMR1, which has a spontaneous retroviral insertional mutation in Abcb1α gene, was used to assess the effects of Abcb1α gene mutation. The brain samples of SAMR1 showed decreased expressions of P-glycoprotein and Abcb1α genes and increased expression of Abcb1b gene, compared with those of SAMP8 mice. The P-glycoprotein expression increased with aging in the brain samples of SAMP8, but not in those of SAMR1. The gene expressions of Abcb1α and Abcb1b increased with aging in the brain samples of SAMP8. Immunosignals of P-glycoprotein were seen in vessel walls, mainly in the cytoplasm of CD34-positive endothelial cells and partially in astrocytes, in all mice. These findings indicate that the expressions of Abcb1α and Abcb1b genes and their gene products, P-glycoprotein, were increased with aging in SAMP8, suggesting age-related response to prevent toxic substance from accumulating in the brains of SAMP8.


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Mortality According to a Prior Assessment of Biological Age
Christopher J. Bulpitt, Riitta L. Antikainen, Hugh L.J. Markowe and Martin J. Shipley

Background: Measures of biological age have not been proven to predict mortality. This study examines whether measuring biological age improves the prediction of mortality. Methods: Prospective study from 1981 to 2001 of 397 male London Civil Servants. Two indices of biological ageing were calculated. Results: 60 men died and both indices of biological ageing were related to survival. In a model that mutually adjusted for both chronological and biological age, biological age using index one was statistically significant with a hazard ratio (HR) of 1.11 per year of age (95% confidence interval 1.01 – 1.21, P=0.03). The useful components of the measures of biological ageing were systolic blood pressure (HR 1.31 for 1SD), albumin, and, to a lesser degree, Erythrocyte Sedimentation Rate (ESR). Greying of the hair, skin inelasticity, arcus senilis, and baldness were not predictors of mortality as measured by our methods. Similarly serum cholesterol, creatinine, calcium and urate could be excluded. A modified index was developed including systolic pressure, ESR, urea, albumin, and bilirubin and had a sensitivity of 78% and specificity of 51% in predicting subjects who died. Conclusion: This study represents ‘proof of principle’ in demonstrating the utility and validity of measuring biological age. The modified index needs to be tested prospectively.


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Comparing Age Effects in Normally and Extremely Highly Educated and Intellectually Engaged 65 - 80 Year-olds: Potential Protection from Deficit Through Educational and Intellectual Activities Across the Lifespan
Vera Schumacher and Mike Martin

Education and cognitive activity have been suggested to protect against cognitive decline in old age. However, little is known about the long-term effects of extremely high levels of education and intellectual activity across the lifespan. The present study investigated the extent to which these two variables may moderate the age-related differences in cognitive performance in old adults. Therefore, story recall, paired-associates learning, reading span and letter digit performance of 62 university professors (mean age = 72.47) were compared with those of a representative sample of 196 participants of the Zurich Longitudinal Study of Cognitive Aging (mean age = 73.04). The results demonstrate that the highly educated sample performed significantly better than the normally educated sample in the paired-associates learning and reading span test. Furthermore, age effects were found in the letter digit as well as in the paired-associates learning test. While the normally educated sample demonstrated an age-related decrease in the paired-associates learning test, the performance of the highly educated sample actually increased with increasing age. These findings suggest that extremely high levels of education and intellectual activity may postpone age-related deficits in paired-associates learning tasks, but not in speed of processing tasks.


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Pathology Associated Memory Deficits in Swedish Mutant Genome-Based Amyloid Precursor Protein Transgenic Mice
Brian J. Hock, Kennon M. Lattal, Laura S. Kulnane, Ted Abel and Bruce T. Lamb

To gain insight into the relationship between pathological alterations and memory deficits observed in Alzheimer’s disease (AD), a number of amyloid precursor protein (APP) transgenic animal models have been generated containing familial AD mutations. The most commonly utilized method involves a cDNA-based approach, utilizing heterologous promoters to drive expression of specific APP isoforms. As a result of the assumptions inherent in the design of each model, the different cDNA-based transgenic mouse models have revealed different relationships between the biochemical, pathological and behavioral alterations observed in these models. Here we provide further characterization of a genomic-based, amyloid precursor protein yeast artificial chromosome transgenic mouse model of AD, R1.40, that makes few assumptions regarding disease pathogenesis to study the relationship between brain pathology and altered behavior. Aged R1.40 transgenic and control mice were tested for learning and memory in the Morris water maze and for working memory in the Y maze. Results from the water maze demonstrated intact learning in the both control and R1.40 mice, but impairments in the long-term retention of this information in the transgenic mice, but not controls. Interestingly, however, long-term memory deficits did not correlate with the presence of Aβ deposits within the group of animals examined. By contrast, age-related working memory impairments were also observed in the Y maze in the R1.40 mice, and these deficits correlated with the presence of Aβ deposits. Our results demonstrate unique behavioral alterations in the R1.40 mouse model of AD that are likely both dependent and independent of Aβ deposition.


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Relationship of Dietary Habits and Obesity to Oxidative Stress in Palauan People: Compared with Japanese and Mongolian People
Fumio Komatsu, Yasuo Kagawa, Terue Kawabata, Yoshinori Kaneko and Kiyomi Ishiguro

The Republic of Palau belongs to Micronesia, and obese people and lifestyle-related diseases are prevalent there. We investigated the relationship of dietary habits and obesity to oxidative stress in Palauan people, as compared with those of Japanese and Mongolian people. A total of 126 healthy Palauan subjects were enrolled. Oxidative stress was evaluated by serum level of reactive oxygen metabolites (ROM). Antioxidant capacity was evaluated by serum level of biological antioxidant potential (BAP). In Palauan subjects, BMI30 was observed in 45.0% of males and 59.1% of females (Japanese: males 1.3%, females 0.8%, Mongolian: males 6.3%, females 14.7%). Palauan subjects consumed 2553 kcal per day (Japanese 2121 kcal, Mongolians 2534 kcal). The ratios of carbohydrate energy to total energy were 59.8 % (Japanese 54.7 %, Mongolians 50.2%). The ratios of fat energy to total energy were 22.9% (Japanese 26.7%, Mongolians 34.5%). ROM levels in Palauan subjects showed higher than those in Japanese subjects, while BAP levels of Palauan subjects did not decrease compared to those of Japanese. ROM levels correlated with body fat ratio, and showed a reverse correlation with handgrip strength. Handgrip strength decreased in the subjects of more than forty years of age. These findings suggest that the obesity in Palauan people may have a connection with high intake of calories through carbohydrate eating rather than through fat eating. Their high oxidative stress may be induced by obesity, and contribute to an early decline of handgrip strength, ultimately in early aging.


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Translational Pharmacology in Aging Men with Benign Prostatic Hyperplasia: Molecular and Clinical Approaches to Alpha₁-Adrenoceptors
Yoshiyuki Kojima, Yasue Kubota, Shoichi Sasaki, Yutaro Hayashi and Kenjiro Kohri

Benign prostatic hyperplasia (BPH) occurs in over 50% of men over 60 years of age, most of whom have lower urinary tract symptoms (LUTS). The incidence of BPH appears to be increasing due to the increased longevity of men. LUTS associated with BPH (LUTS/BPH) greatly affects the patient’s quality of life. Physicians should be aware of other issues associated with advancing age, such as cardiovascular diseases, sexual dysfunction and cataract, that may complicate the treatment of aging men with LUTS/BPH; therefore, management of LUTS/BPH requires careful selection of the most appropriate treatment for each patient. Alpha1-adrenoceptor (α₁-AR) stimulation plays an important role in the regulation of prostate smooth muscle contraction. Recent remarkable advances in molecular biology offer the possibility of new findings about the role of α₁-AR subtypes and new therapeutic options for BPH; however, even though α₁-AR antagonists are used as the first-line medical treatment for patients affected by LUTS/BPH, responses to α₁-AR antagonists differ among patients. The risks of unexpected adverse events, acute urinary retention and the need for invasive therapy also differ among patients. Translational pharmacology is the collaboration between researchers and clinicians to discover more effective medical therapies and to identify new drugs for various diseases. This review summarizes the recent molecular and physiological findings of α₁-AR subtypes and discusses potential new strategies for BPH medical treatment. In the future, the promise of genetic-based prescriptions and therapeutic plans as a useful strategy to improve clinical outcomes of BPH medical therapy may become credible and warrants further investigation.


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Short- and Long-Term Survival of Nonsurgical Intensive Care Patients and its Relation to Diagnosis, Severity of Disease, Age and Comorbidities
Peter A. Kaufmann, Karl H. Smolle and Guenter J. Krejs

Objective: To identify variables associated with mortality in the ICU and 1 year following discharge. Design: Prospective observational cohort study. Setting: ICU of a tertiary care center and university hospital. Patients: A total of 3,119 medical and neurological intensive care patients. Measurements and Main Results: Pre-admission health status was quantified by the sum of risk factors and chronic diseases. Severity of the acute disease was estimated by counting the number of organ dysfunctions and the Acute Physiology Score. Concerning the primarily affected organ system, ICU mortality was highest in hematological diseases (63%) and 1-year mortality was 82%. Lowest death rates were observed with metabolic (ICU 4%, 1-yr 18%) and psychiatric diagnoses (ICU 5%, 1-yr 13%). Greater severity of illness with the need for mechanical life support was associated with decreased 1-year survival. In the respiratory and in renal diseases, the artificial support of the primarily affected organ system incurred an ICU mortality equaling the average (23%) or below (14%) that of the whole ICU population. Pre-admission health status increased the probability of developing multiple organ failure and worsened outcome 1 year after discharge in non-cardiovascular patients. Age showed a weak correlation with chronic diseases and severity of the acute illness and was related to long-term, but not short-term survival. Conclusions: The most important risk factors associated with short- and long-term mortality in non- surgical intensive care patients are disease severity and the primarily affected organ system that necessitates admission. The artificial support of this organ system can improve only short-term outcome.