Current Aging Science - Volume 2, Issue 1, 2009

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Human mortality data show stabilization in mortality rates at very late ages. But human mortality data are difficult to interpret because they are affected by changing medical practices and other historically variable causes of death. However, in the 1990s, data from a variety of labs showed that the mortality rates of medflies, fruit flies, wasps, yeasts, and nematodes also stabilize at very late ages. These reproducible “mortality-rate plateaus” forced biologists to develop theories for their existence. There are two main theories of this kind. “Lifelong heterogeneity” theories suppose that highly robust subcohorts are more abundant at later ages because less robust subcohorts have mostly died off. On this type of theory, aging does not stop; aging continues inexorably in all individuals. In contrast, in evolutionary theories for mortality-rate plateaus, based on the eventual plateaus in Hamilton's Forces of Natural Selection at late ages, aging does indeed stop. A variety of experiments have cast doubt on lifelong heterogeneity theories as explanations of mortality-rate plateaus. A few experiments have corroborated the Hamiltonian theory. This has the important corollary that it appears to be possible for aging to stop, at sufficiently late ages, at least among some populations. The implications of this result for aging research are profound. Most importantly, it suggests the possibility that the physiology of adults undergoing aging may be substantially different from the physiology of life after aging.

The causes of aging and determinants of maximum lifespan in animal species are multifaceted and complex. However, a wealth of experimental data suggests that mitochondria are involved both in the aging process and in regulating lifespan. Here we outline a somatic cell depletion (SCD) model to account for correlations between: (1) mitochondrial reactive oxygen species and lifespan; (2) mitochondrial antioxidant enzymes and lifespan; (3) mitochondrial DNA mutation and lifespan and (4) cellular stress resistance and lifespan. We examine the available data from within the framework of the SCD model, in which mitochondrial dysfunction leading to cell death and gradual loss of essential somatic cells eventually contributes to the decline in physiological performance that limits lifespan. This model is useful in explaining many of the mitochondrial manipulations that alter maximum lifespan in a variety of animal species; however, there are a number of caveats and critical experiments outstanding, and these are outlined in this review.

Oxidative stress induces several diseases and early aging. Previously, we reported that Mongolians are exposed in high oxidative stress, which may cause their early aging. In this study, to know the reason of high oxidative stress, we measured hair metals. This investigation was performed in Murun city, in the northern area of this country, and 469 healthy subjects, ranging from 10 to 82 years of age, were randomly enrolled. Oxidative stress was evaluated by the levels of serum reactive oxygen metabolites (ROM), malondialdehyde-modified low-density lipoprotein (MDA-LDL) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Antioxidant capacity (AOC) was estimated by the levels of biological antioxidant potential (BAP) and superoxide dismutase (SOD) activity. Scalp hair metals were measured using an inductively coupled plasma mass spectrometry method. Murun subjects showed high ROM levels of 394±75 Carr U (n=342), compared with Japanese healthy subjects (n=356, 326±51 Carr U, p<0.001). MDA-LDL and 8-OHdG levels also showed high levels. While, BAP levels of Murun subjects were 2263±203μmol/L (n=210), Japanese subjects (n=356, 2087±215μmol/L, p<0.001). SOD activities were also high, suggesting that the high oxidative may accelerate the state of AOC. Murun subjects demonstrated high accumulation of several metals in the hairs. In particular, Mn accumulation exhibited from 2 fold to 40 fold increases of Japanese standard. These findings are indicative that the high Mn accumulation may contribute to the high oxidative stress. The mechanism of its high accumulation was not explained by food materials or drinking water. We should further investigate another influence such as sandy wind. In order to suppress the high oxidative stress, elimination of the high Mn accumulation should be urgently studied.

In the literature it is commonly reported that several spatial abilities decline with normal aging, even though such a decline is not uniform. So far, it is not yet clear which spatial components present a normal age-related decline, which ones are preserved and at what point the deficit is so severe to represent an index of mild cognitive impairment (MCI) or a symptom of potential degenerative progression as in the early-stage Alzheimer's disease (AD). In particular, AD (from early onset) is characterised by impairments in constructive abilities, visuospatial intelligence, spatial shortterm memory deficits, and disorders of spatial orientation (topographical disorientation). MCI indicates a condition, generally affecting older individuals, characterized by cognitive deficits including memory and/or non memory impairments and at high risk of progression to dementia. Three MCI subgroups have been distinguished and a very high risk of developing AD is associated to the amnestic MCI subtypes. Further, recent studies have suggested that the allocentric component of spatial memory might be taken as predictor of AD from MCI. Given the frequency of visuospatial deficits in early-stage AD, evaluation of visuospatial processes is a promising approach to find predictive markers of AD. Here we report a review of the literature exploring specific visuospatial components in normal aging, MCI, and AD. In this way we could shed some light on the role of these components in the progression from MCI to AD and pave the way for future studies.

In this investigation we assessed the extent to which young and elderly individuals become dependent on the specific visual situation present during practice of an interceptive task. Young and elderly participants practiced extensively a task of intercepting a virtually moving target under full vision or visual occlusion of the last 600 ms of target displacement. Before and after practice they were assessed in four visual conditions varying the time interval of visual display. The results showed that the elderly practicing under full vision had a progressive increase of temporal errors as a function of the period of visual occlusion after task acquisition. The elderly practicing under visual occlusion, conversely, achieved improved performance only in the visual condition experienced during task acquisition. Young individuals showed greater adaptability, presenting similar performance across visual conditions. Development of specific visuomotor integration only for the elderly seems to be related with the higher status that vision holds for movement control at this age.

Introduction: Clinical laboratory data are crucially important for the diagnosis, prognosis and therapy of agingrelated diseases. The age-dependent changes in the findings of routine clinical-chemistry analyses may influence the evaluation of health status of the elderly people. Serum endogenous antioxidant levels and lipid profiles are considered to be related to the progress of age-related diseases. Analyses of these routine parameters are also important for the evaluation in the elderly. Although the analyses of serum biochemical parameters are important, there have been not enough data on changes in the levels of parameters with aging in both genders. However, elderly people generally suffer from aging-related diseases or may be using some medication that interferes with the accuracy of the result; it is thus preferred that the same procedures be applied in aged rats as a model of human aging. Methods: Aged Sprague-Dawley rats (24 months) of both genders were used in the current study. Serum total protein, albumin, bilirubin, uric acid, lipid profiles, iron, and total iron-binding capacity levels were determined on the same day of collection by standard clinical chemistry laboratory methods. Results: Serum endogenous antioxidant parameters such as uric acid and bilirubin levels varied with gender in spite of almost no changes in the serum albumin and total iron binding capacity levels. Among the main parameters studied, lipid profile, conjugated bilirubin, and uric acid levels of male rats were significantly higher than in the aged female group. On the other hand, serum unconjugated bilirubin and iron levels were all found to be lower in the aged male group. Conclusion: Our findings support our conviction that serum biochemical parameters of aged rats have a controlling role in differing regulating mechanisms through gender differences. The gender-related data on these main serum clinical chemistry parameters in aged rats would be useful in studies of aging-related disorders using this model.

Low frequency transcutaneous sensory nerve stimulation (LF-SNS) [International Patent PCT/AU2004/001079:“nerve function and tissue healing” (Khalil, Z.)] improves sensory nerve function and accelerates wound healing of older animals. Intervention: Double blind, placebo controlled randomised trial of LF-SNS for 5 minutes, twice daily for up to 12 weeks, on healing of chronic venous leg ulcers in older people. Four layer compression bandaging was the standard therapy. Outcome measures (methods): Wound healing and the rate of epithelialisation (calculated from serial wound area estimation), microvascular blood flow (measured using LASER Doppler flowmetry), transcutaneous oxygen tension (measured using a transcutaneous oxygen monitor, TCM&trade400 Radiometer). Sensory nerve activity (assessed via measuring electrical cutaneous perception threshold using the Neurometer®CPT and the flare response to 5% capsaicin (a selective activator of C fibres). Participants: 14 older people with chronic venous ulcers randomly allocated to active (mean age 74.8±2.3 years) and 15 to Sham nerve stimulation (mean age 76.5±2.6 years). Results: Microvascular blood flow improved in all participants. A high proportion of wounds healed (∼ 60%). There were trends for better C-fibre function and faster healing rates in the Active group (1.1±0.3 cm2/wk) compared to the Sham group (0.6±0.2 cm2/wk) but failed to reach statistical significance due to the small sample size. Conclusions: The improvement in microvascular blood flow in both groups was an unexpected finding that has not previously been described. Most likely this was due to the four layer compression bandaging provided to all participants. Improved microvascular blood flow may be a significant contributor to wound healing. The observed trends to increased healing rates and improvements in C-fibre function in the actively stimulated group compared to the sham group warrant further studies of LF-SNS as an adjunct therapy for chronic venous leg ulcers. An exploration of the possibility that LFSNS induced-improvement in C-fibre function could protect against future ulceration is also warranted.

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