Current Aging Science - Volume 3, Issue 2, 2010

The molecular mechanisms that cause physiological aging are still not completely understood, most likely because of the complex nature of the aging process. Recent discoveries on segmental progeroid syndromes emphasize the importance of studying rare diseases to discover more common mechanisms. Since the identification of mutations in the LMNA gene that causes the segmental progeroid syndrome, Hutchinson-Gilford progeria syndrome (HGPS), there has been an increasing interest in the potential role for lamins in the normal aging process. Recent data provide support for the shared mechanisms between natural and pathological aging, and show that further studies of HGPS and segmental progeroid syndromes will be of use in solving the aging puzzle. In this review, we summarize the recent findings and discuss the existing evidence for an important functional link between lamins and the aging process. In addition, we discuss the evidence for a mechanism in which defects in lamins result in genomic instability and senescence.

Sarcopenia, the progressive loss of muscle mass with age, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement and a decline in strength and power. Sarcopenia is a highly significant public health problem. Since these age-related changes in skeletal muscle are largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostatis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. We and other researchers demonstrated that a disruption of Akt-mTOR and RhoA-SRF signaling but not Atrogin-1 or MuRF1 contributes to sarcopenia. In addition, sarcopenia seems to include a marked loss of fibers attributable to apoptosis. This review deals with molecular mechanisms of muscle atrophy and provides an update on current strategies (resistance training, myostatin inhibition, treatment with amino acids or testosterone, calorie restriction, etc) for counteracting this loss. Resistance training in combination with amino acid-containing nutrition would be the best candidate to attenuate, prevent, or ultimately reverse age-related muscle wasting and weakness.

The discovery of novel uncoupling proteins (UCP2 and UCP3) over 10 years ago heralded a new era of research in mitochondrial uncoupling in a diverse range of tissues. Despite the research vigor, debate stills surrounds the exact function of these uncoupling proteins. For example, the level of uncoupling, the mechanism and mode of action are all under-appreciated at this point in time. Our recent work has used genetic mouse models to focus on the physiological relevance of UCP2. We have used these mouse models to better appreciate the role UCP2 in human health and disease. In this review we focus on new research showing that UCP2 promotes longevity by shifting a given cell towards fatty acid fuel utilization. This metabolic hypothesis underlying UCP2-dependent longevity suggests that UCP2 is critically positioned to maintain fatty acid oxidation and restrict subsequent oxidative damage allowing sustained mitochondrial oxidative capacity and mitochondrial biogenesis. These mechanisms converge within the cell to boost cell function and metabolism and the net result promotes healthy aging and increased lifespan. Finally, UCP2 is a useful dietary and therapeutic target to promote lifespan and is an important mitochondrial protein connecting longevity to metabolism.

Over the last decades estrogen has been recognized to be involved in normal brain function due to its neurothrophic and neuroprotective effects. Estrogen is intimately associated with neuronal survival, mitochondrial function, neuroinflammation and cognition through genomic as well as non-genomic pathways. It is also known that the neuroprotective actions mediated by estrogens are interlinked with the insulin-like growth factor-1 (IGF-1) signaling pathway. This review is mainly devoted to explore the physiological and pathophysiological effects of estrogen and its signaling pathways in the brain. The molecular mechanisms underlying these effects are also debated. Finally, we discuss the potential neuroprotection afforded by estrogens in Alzheimer's disease pathophysiology focusing in the “window of opportunity” for the initiation of estrogen therapy as a critical factor in the fight against neurodegeneration.

Previously we reported that Apolipoprotein E (ApoE) ε4 negatively affects performance in the novel-image-novel- location (NINL) object recognition test in healthy non-demented elderly human study participants. In this study, the participants were invited to return for testing sessions 6 and 18 months after the baseline session. Using a longitudinal study design, effects of ε4 on NINL test performance were assessed in study “dropouts”, participants that did not return for the second and/or third session(s), and “finishers”, participants that returned for all sessions. There were effects of ε4 on dropout rates and NINL total scores as well as sub-scores in both dropouts and finishers. NINL total score was a predictor of ε4 participant dropout. Compared to non-ε4 dropouts, ε4 dropouts had lower NINL scores. In contrast, ε4 finishers had higher NINL scores than non-ε4 finishers. Thus, the NINL test could be a valuable tool in detecting preclinical signs of age-related cognitive impairments, particularly those associated with ε4 risk.

Background: The UK national Dementia Strategy clearly outlines a case for early detection and diagnosis of dementia. There is thus a need for a brief screening test for dementia in primary care, which can be administered and scored easily. Aim: To compare the performance of two cognitive scales, Mini-Mental State Examination (MMSE) and 6 Item Cognitive Impairment Test (6-CIT), as screening test for dementia in a naturalistic setting. Methods: 209 subjects referred to Old Age Psychiatry service were retrospectively studied. Their MMSE and 6-CIT scores were used to compare sensitivity, specificity and the Receiver Operating Characteristic (ROC) Curves for diagnosis of dementia. Results: The correlation between the MMSE score and 6-CIT score is - 0.822. The MMSE has a sensitivity of 79.7% and specificity of 86.4% (cut-off 23/24). The 6-CIT has a sensitivity and specificity of 82.5% and 90.9% respectively (cut-off 10/11). The sensitivity of the 6-CIT increases to 90.2% at a lower cut-off of 9/10, but the corresponding specificity drops to 83.3%. Conclusion: The 6-CIT is a brief and simple test of cognition, which correlates reasonably well with the MMSE in a naturalistic setting. Compared with the MMSE it performs well as a screening instrument for dementia, which makes it a more appropriate test for primary care usage.

The proportion of older persons is increasing in developed and developing countries: this aging trend can be viewed as a two-edged sword. On the one hand, it represents remarkable successes regarding advances in health care; and on the other hand, it represents a considerable challenge for health systems to meet growing demand. A growing disequilibrium between supply and demand may be particularly challenging within publicly funding health systems that ‘guarantee’ services to eligible populations. Rehabilitation, including physical therapy, is a service that if provided in a timely manner, can maximize function and mobility for older persons, which may in turn optimize efficiency and effectiveness of overall health care systems. However, physical therapy services are not considered an insured service under the legislative framework of the Canadian health system, and as such, a complex public/private mix of funding and delivery has emerged. In this article, we explore the consequences of a public/private mix of physical therapy on timely access to services, and use the World Health Organization (WHO) health system performance framework to assess the extent to which the emerging system influences the goal of aggregated and equitable health. Overall, we argue that a shift to a public/private mix may not have positive influences at the population level, and that innovative approaches to deliver services would be desirable to strengthen rather than weaken the publicly funded system. We signal that strategies aimed at scaling up rehabilitation interventions are required in order to improve health outcomes in an evolving global aging society.

Objectives: The main objective of this study is to verify the existence of a direct relation between age, ageing and hospital resources utilization. Methods: For this purpose, we use not only population variables, but also clinical parameters such as severity and complexity, as proxy of consumption and hospital costs. Through a comprehensive statistical analysis, quantitative variables of the Spanish Minimum Data Set of year 2006 (length of stay, relative weight, number of diagnoses and procedures) according to age groups and gender, types of admission (emergency or scheduled) and discharge (alive or dead), measuring the severity by weight, complications, comorbidities and mortality, and complexity by weight and length of stay. Results: The highest severity was observed in 65-69 year-old males and the highest complexity in 75-79 year-old males and 85-89 year-old females (p<.0001). The severity and complexity are also higher among 65-69 year-old males and 70- 79 year-old patients of both sexes with emergency access (p<.0001). The deceased patients are more aged with higher severity and complexity than the survivors (p<.0001). Conclusions: The age per se is not directly related to consumption of hospital resources. Therefore, aging does not necessarily imply higher consumption or increased hospital costs. Emergency admitted in-patients are older and more severe and complex than the scheduled ones, thus consuming more resources and implying higher hospital costs; the same is true for the deceased versus the survivors.