Current Aging Science - Volume 1, Issue 2, 2008

There is a critical shortage of organs available for donation to patients suffering from degenerative diseases of various organ systems. This shortage becomes more severe yearly, as the aging population grows and such diseases become more common. The fields of regenerative medicine and tissue engineering now offer hope for these aging patients with new advances in material science, cell transplantation, and bioengineering. Novel methods and materials to construct biological substitutes for diseased and injured tissues are being developed, and the goal is to restore and maintain normal function to the patient. The field of stem cell research is rapidly advancing, offering unforeseen options for treatment. For example, therapeutic cloning, where an enucleated oocyte receives a donor cell nucleus, yielding pluripotent stem cells, offers a potentially limitless source of cells for tissue engineering applications. However, recent discoveries in this field indicate that the use of non-controversial cells and tissues also has enormous potential for tissue engineering purposes. This article gives an overview of recent advances in regenerative medicine and describes their applications in tissue and organ replacement technology, as well as how these technologies offer new therapies to a person facing end-stage organ failure. There is a growing optimism that the successes in this field will achieve the goal of significantly extending the life of the patient.

Mongolians are known to have relatively short life expectancy. In order to examine the role of dietary habits in the early aging of Mongolians, the food intake inquiry, anthropometric measurements and blood clinical tests were performed for 365 healthy inhabitants in Murun, a northern Mongolia city, and compared to those of Japanese. Murun inhibitants were found to have a characteristic dietary habit of taking large amounts of meat, milk, dairy products and wheat flour products, in contrast little vegetables, fruits and fishes. The daily calorie intake of the adults was estimated to be 2,525 kcal, and the fat/total calorie ratio was calculated 33.7%, about 1.3-fold higher than that of Japanese. The intake ratio of fatty acid from the Mongolian foods, saturated : mono-unsaturated : poly-unsaturated fatty acids (PUFA) ratio, was 10.3 : 7.8 : 3.0. Results of blood clinical tests showed significantly higher levels of serum triglycerides, low-density lipoprotein cholesterol (LDL) and homocysteine, and lower levels of high-density lipoprotein cholesterol (HDL), n-3 PUFA, folic acid and adiponectin, in comparison with those of Japanese. In addition, the Mongolians were also found to have significantly high levels of oxidative stress markers, such as serum malondialdehyde-modified LDL (MDA-LDL), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum reactive oxygen metabolites (ROM). The serum ROM level in the Mongolians seemed to associate with their body fat ratio (p<0.05), and was significantly inverse-correlated to handgrip strength (p<0.001). Obesity was observed at a high incidence in the subjects over 30-year old, and over 40-year old their handgrip ability was markedly decreased. These findings suggest that in the Mongolians the dietary habits associate with their lifestyle-related diseases and early aging, and the improvement of dietary habits is an effective strategy for health promotion of the inhabitants.

The endocrine system is as affected by aging as are other systems. The effect of aging on the hypothalamuspituitary- thyroid function is still controversial. Human aging was reported as associated with a decrease in thyrotropin (TSH) secretion, but increased TSH levels in relatively healthy elders are also reported. The main point discussed is whether this increase in the immunoreactive TSH of aged subjects, and related changes in thyroid function, are “physiologic” consequences of aging on the hypothalamus-pituitary-thyroid axis or are induced by non-thyroid illnesses and/or drug use, frequent in the elderly. There are strong evidences of decreased hypothalamus-pituitary-thyroid axis activity as well as decreased thyroxine metabolism (5'-deiodination) in humans, and other mammals. For now, we must consider that the hypothalamus-pituitary-thyroid axis is affected at all three levels by normal aging, and the mild state of “total” hypothyroidism during aging is completed by a reduced response of target cells/tissues to thyroid hormones. Despite the decreased response of the old rat thyroid to TSH there is no decrease in the glands mass. Ras proteins are involved in the transduction of growth factor signals by surface receptors, in thyroid as well as in other tissues, and are key components of downstream signaling through several pathways. Ras activation of Raf, and of extracellular-signal-regulated kinases (ERK) is an important signaling pathway for many Ras effects. Very little is known about the modulation of Ras expression in the aging thyroid. We detected an increase in Ras expression in thyroids of old rats, but the signal transduction by pERK was decreased, suggesting that another RAS-signaling pathway could be activated and responsible for the maintenance of the thyroid volume.

The impact of intraventricular ciliary neurotrophic factor (CNTF) on motor function in aged rats was evaluated. Spontaneous locomotion and motor coordination were quantified in young (5-6 months) and aged (24-25 months) rats. Relative to young animals, aged rats were significantly less active, fell more rapidly from a rotating rod, and were unable to maintain their balance on a wooden beam. Aged animals received bilateral intraventricular implants of polymerencapsulated fibroblasts that were genetically modified to secrete CNTF. Controls received either no implant or capsules loaded with mock transfected cells. One month after implantation the aged animals that received CNTF implants were significantly more active and were improved on the rotorod and beam balance tests. The improvement in performance on the rotorod and beam balance tests was dependant on the task difficulty and dissipated at higher rotations (rotorod) and smaller beam widths (beam balance). No recovery was seen in aged animals receiving control implants. Postmortem removal of the encapsulated cells confirmed that they continued to secrete CNTF. These data are the first to suggest that intracerebral delivery of CNTF might be useful for slowing or reversing age-related changes in motor function.

Evidence suggests chronic inflammation and iron accumulation may play a role in the pathogenesis of Parkinson's disease (PD) as inflammation and iron levels increase with age and appear in the disease pathology. It is hypothesized that an aggravated inflammatory response and iron accumulation, as a function of age, increase oxidative stress and participate in the pathogenesis of PD. Intracranial injection of the bacterial endotoxin, lipopolysaccharide (LPS), has been shown to induce microglia activation, oxidative stress, mitochondrial impairment, iron accumulation, and dopaminergic neurodegeneration within the substantia nigra. We tested the hypothesis that injection of LPS into the striatum would increase iron accumulation in the substantia nigra of aged rats compared to young ones. Our results showed that four weeks post injection, LPS significantly increased microglia activation, lipid peroxidation, ferritin expression, and total nigral iron content in aged rats. In addition, LPS significantly altered the turnover ratio of homovanillic acid to dopamine. Thus, an age-related increase in iron as well as susceptibility to inflammation may play an important role in PD-related neurodegeneration, as free radicals produced from the inflammatory response can become more toxic through increased ferrous iron catalyzed Fenton Chemistry. This may enhance oxidative stress, exacerbate microglia activation, and drive the progression of PD.

Since the earliest descriptions of Alzheimer’s disease (AD), the presence of senile plaques (SP) and neurofibrillary tangles (NFT) have been regarded as the typical pathological hallmarks of the disease. Studies over the last twenty years, however, have reported a considerable degree of heterogeneity within the AD phenotype and as a consequence, an overlap between the pathological features of AD not only with normal aging, but also with disorders related to AD. This review discusses: 1) the degree of heterogeneity within AD, 2) the concept of an ‘interface’ between disorders, 3) the nature and degree of the interface between AD and normal aging, vascular dementia (VD), the tauopathies, synucleinopathies, and prion disease, and 4) whether the original status of AD should be retained or whether AD, normal aging, and the related disorders should be regarded as representing a ‘continuum’ of neuropathological change.

The following review was constructed as a concept paper based on a recent workshop on neurodegenerative disease sponsored by the National Institute on Aging (NIA), the American Geriatric Society (AGS), and the John A. Hartford Foundation. The meeting was entitled “Thinking, moving and feeling: Common underlying mechanisms? 4th Annual Bedside-to-Bench Conference” and had the purpose to connect current basic and clinical findings on common brainrelated alterations occurring with aging such as depression, movement disorders, and cognitive decline. Many prominent researchers expressed their opinion on aging and it was revealed that age-related brain dysfunction of any kind seems to share several risk factors and/or pathways. But can something be done to actively achieve “successful aging”? In this review, based largely on the workshop and current literature, we have summarized some of the current theories for depression, movement and cognitive impairment with aging, as well as potential preventive measures. We have also summarized the emerging need for relevant animal models and how these could be developed and utilized.

Alzheimer's dementia is one of the most commost mental health disorders associated with aging. In its earlier stages sufferers live independently but gradually rely increasingly on loved ones or formal carers for support as the illness progresses. Its treatment involves both medical and social care. This study assesses the impact of outpatients’ care and cholinesterase inhibitors in patients being treated for Alzheimer's dementia. The needs and quality of life of patients attending an outpatients dementia care service were assessed using the Camberwell Assessment of Need for the Elderly (CANE) and Quality of Life in Alzheimer's Disease: Patient and Caregiver report. Other tools used were the Problems Checklist and Carer Strain, the Minimental State Examination (MMSE) and a proforma to obtain sociodemographic details. All patients who had informal care were assessed using the questionnaires. 104 patients were seen of whom 34 were new and 70 were follow-up patients. 43 patients lived alone while the rest lived with their spouses or other relatives such as children. There was reduction in the number of CANE unmet needs and increased combined Quality of Life in Alzheimer's Dementia scores in the first three months amongst the newly referred patients. The findings suggest that outpatients' dementia care and prescribing of cholinesterase inhibitors helped to meet the needs of patients and improve patients' quality of life in first three months.

As there is a rapid rise in the elderly population and incidence of related old age diseases, an emerging social challenge is to maintain health throughout ones lifespan. In this context, the present book is timely written by experts in the subject and presents state-of-art status of research on hormesis and aging. Although the book is multi-authored, chapters are highly coordinated. It aims to explore whether hormesis can be used for healthy aging of human beings and presents excellent and interesting information on hormesis with respect to aging. The editors, Eric Le Bourg and Suresh I.S. Rattan, are leading researchers and popularly known for their longstanding contributions in the area of aging and hormesis. The book comprises 10 well-written chapters covering a wide range of topics on hormesis and aging. Each chapter is thoroughly discussed and provides new information. The first two chapters deal with detailed introduction of hormesis and aging, the next five chapters discuss hormetic effects of various types of stresses, and the last three chapters are concerned with clinical applications of hormesis. At the end, it is concluded how hormesis can be useful for healthy aging, though the underlying mechanism of action is not clearly understood. The book begins with an excellent introduction and brief historical analysis of hormesis and aging by the editors. The second chapter by Edward Calabrese further explains the phenomenon of hormesis and focuses on its use in gerontological research. The third chapter written by Alexander Vaiserman describes the beneficial effects of low dose irradiation on the longevity of fruitflies, nematodes, rodents and human beings. The next chapter by Eric Le Bourg presents results of hormetic effects of hypergravity on aging and longevity of D. melanogaster. The following chapter by Jesper Sorensen and colleagues focuses on the use of extreme temperatures, either hot or cold in D. melanogaster. The next chapter by the editor Suresh Rattan himself describes the effects of mild stresses on human cells, mainly fibroblasts. Focusing on rodents and human beings, Li Li Ji shows that an increased physical activity can act as a mild stress with hormetic effects. The last three chapters are concerned with clinical applications of hormesis. Brian Morris discusses the use of hormetic compounds for health benefits. Pasquale Abete and Franco Rengo present evidences to show how mild stress can be used to protect the aging heart from pathological insults. Akmal Safwat argues that low dose whole body irradiation enhances the efficiency of immune system. Finally, in conclusion, all authors emphasize the perspectives for human beings mentioning that hormesis can be used as an effective anti-aging, health-promoting and lifespan-extending strategy. The book is thought provoking and opens an exciting new area for detailed study. It would be highly useful for young researchers in biogerontology as well as for the established biogerontologist to analyse their results in the light of hormetic effects. Thus the book is worth reading by not only biogerontologists but by all those who are interested in understanding the hormetic approach for healthy aging.