Amyotrophic lateral sclerosis (ALS), first described by Jean-Martin Charcot in the 1870s, is an age-related disorder that leads to degeneration of motor neurons. The disease begins focally in the central nervous system and then spreads relentlessly. The clinical diagnosis, defined by progressive signs and symptoms of upper and lower motor neuron dysfunction, is confirmed by electromyography. Additional testing excludes other conditions. The disease is heterogeneous, but most patients die of respiratory muscle weakness less than 3 years from symptom-onset. Like other age-related neurodegenerative diseases, ALS has genetic and environmental triggers. Of the five to 10% of cases that are inherited, mutations have been discovered for a high proportion. In addition to genetic factors, age, tobacco use, and athleticism may contribute to sporadic ALS, but important etiologies are unidentified for most patients. Complex pathophysiological processes, including mitochondrial dysfunction, aggregation of misfolded protein, oxidative stress, excitotoxicity, inflammation and apoptosis, involve both motor neurons and surrounding glial cells. There is clinical and pathological overlap with other neurodegenerative diseases, particularly frontotemporal dementia. The mechanisms leading to disease propagation in the brain are a current focus of research. To date, one medication, riluzole, licensed in 1996, has been proved to prolong survival in ALS. Numerous clinical trials have so far been unable to identify another neuroprotective agent. Researchers now aim to slow disease progression by targeting known pathophysiological pathways or genetic defects. Current approaches are directed at muscle proteins such as Nogo, energetic balance, cell replacement, and abnormal gene products resulting from mutations. Until better understanding of the causes and mechanisms underlying progression lead to more robust neuroprotective agents, symptomatic therapies can extend life and improve quality of life. Palliative care programs such as hospice give emotional and physical support to patients and families throughout much of the disease course.
There is a growing scientific agreement that the cellular redox regulators such as antioxidants, particularly the natural polyphenolic forms, may help lower the incidence of some pathologies, including metabolic diseases like diabetes and diabesity, cardiovascular and neurodegenerative abnormalities, and certain cancers or even have anti-aging properties. The recent researches indicate that the degree of metabolic modulation and adaptation response of cells to reductants as well as oxidants establish their survival and homeostasis, which is linked with very critical balance in imbalances in cellular redox capacity and signaling, and that might be an answer the questions why some antioxidants or phytochemicals potentially could do more harm than good, or why some proteins lose their function by increase interactions with glyco- and lipo-oxidation mediates in the cells (carbonyl stress). Nonetheless, pursue of healthy aging has led the use of antioxidants as a means to disrupt age-associated physiological dysfunctions, dysregulated metabolic processes or prevention of many age-related diseases. Although it is still early to define their exact clinical benefits for treating age-related disease, a diet rich in polyphenolic or other forms of antioxidants does seem to offer hope in delaying the onset of age-related disorders. It is now clear that any deficiency in antioxidant vitamins, inadequate enzymatic antioxidant defenses can distinctive for many age-related disease, and protein carbonylation can used as an indicator of oxidative stress associated diseases and aging status. This review examines antioxidant compounds and plant polyphenols as redox regulators in health, disease and aging processes with hope that a better understanding of the many mechanisms involved with these distinct compounds, which may lead to better health and novel treatment approaches for age-related diseases.
We are expected to live longer than if we had been born 100 years ago however, the additional years are not necessarily spent in good health or free from disability. Body composition changes dramatically over the course of life. There is a gradual increase in body weight throughout adult life until the age of about 60–65 years. In contrast, body weight appears to decrease with age after the age of 65–75 years, even in those demonstrating a previous healthy body weight. This age related decrease in body weight, often called unintentional weight loss or involuntary weight loss can be a significant problem for the elderly. This has been shown to be related to decline in appetite and food intake is common amongst the elderly and is often referred to the anorexia of aging. Underlying mechanisms regulate energy homeostasis and appetite may change as people age. In this review, peripheral factors regulating appetite have been summarized in regards to their age-dependent changes and role in the etiology of anorexia of aging. Understanding the alterations in the mechanisms regulating appetite and food intake in conjunction with aging may help inform strategies that promote healthy aging and promote health and wellbeing in the elderly years, with the end goal to add life to the years and not just years to our lives.
Declines in maximal aerobic power and skeletal muscle force production with advancing age are examples of functional declines with aging, which can severely limit physical performance and independence, and are negatively correlated with all cause mortality. It is well known that both endurance exercise and resistance training can substantially improve physical fitness and health-related factors in older individuals. Circuit-based resistance training, where loads are lifted with minimal rest, may be a very effective strategy for increasing oxygen consumption, pulmonary ventilation, strength, and functional capacity while improving body composition. In addition, circuit training is a time-efficient exercise modality that can elicit demonstrable improvements in health and physical fitness. Hence, it seems reasonable to identify the most effective combination of intensity, volume, work to rest ratio, weekly frequency and exercise sequence to promote neuromuscular, cardiorespiratory and body composition adaptations in the elderly. Thus, the purpose of this review was to summarize and update knowledge about the effects of circuit weight training in older adults and elderly population, as a starting point for developing future interventions that maintain a higher quality of life in people throughout their lifetime.
Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive “reporter cells” that are not well studied in AD. In the present study, we analyzed an array of glycolytic and related enzymes and intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age-matched controls (AC) and young adult controls (YC). AD is characterized by higher activities of hexokinase, phosphofructokinase, and bisphosphoglycerate mutase and bisphosphoglycerate phosphatase in RBCs. In our study, we observed that glycolytic and related enzymes displayed significantly lower activities in AC. However, similar or significantly higher activities were observed in AD and NA groups as compared to YC group. 2,3-diphosphoglycerate (2,3-DPG) levels were significantly decreased in AD and NA patients. The pattern of changes between groups in the above indices strongly correlates with each other. Collectively, our data suggested that AD and NA patients are associated with chronic disturbance of 2,3-DPG metabolism in RBCs. These defects may play a pivotal role in physiological processes, which predispose elderly subjects to AD and NA.
Alzheimer’s disease (AD) is associated with widespread structural and functional brain alterations. The current study examined the gray matter (GM) voxel based morphometric (VBM) correlates of cognitive and clinical severity scores in patients with AD. The study included 34 patients with AD according to NINCDS/ADRDA AD criteria and 28 matched elderly controls. All subjects were clinically evaluated using Hindi Mental Status Examination (HMSE), Everyday Abilities Scale for India (EASI) and the Clinical Dementia Rating (CDR) scale. The structural Magnetic Resonance Imaging (MRI) data were acquired using a 3 Tesla MRI scanner and VBM analysis was performed using VBM5.1 toolbox. The patients with AD had significantly lower GM volume, white matter volume and total brain volume as compared to controls. The HMSE scores were positively correlated (p=0.009) and EASI (p=0.04) & CDR (p=0.0004) were negatively correlated with the total GM volumes in patients with AD. The VBM analysis revealed diffuse GM atrophy in patients with AD. Frontal& temporal GM volumes were positively correlated with the HMSE scores. Thus the results of the study replicate the previous observations of generalized GM atrophy, in an Indian sample with AD. The cognitive decline, clinical dementia severity and impairment in activities of daily living were correlated whole brain GM and WM volumes as well as with specific brain regional atrophy in AD. However further studies with larger samples & with more detailed cognitive evaluation are required for confirmation & validation of the relationship between regional morphometric abnormalities and cognitive deficits in AD.
In the present study, we investigated the possible additive effects of epilepsy and aging on the expression of m1 muscarinic acetylcholine receptors (AChR) in the rat hippocampus. Young (3 months) and Aged (20 months) male, Wistar rats were treated with pilocarpine to induce status epilepticus (SE). Immunohistochemical procedure for m1 AChR detection was performed 2 months after pilocarpine-induced SE. In the CA1 pyramidal region m1 AChR staining was significantly decreased in aged epileptic animals when compared to young epileptic and aged control rats, indicating that the aging effect is worsened by the epileptic condition. However, the Nissl-stained cell analysis indicated that the number of pyramidal CA1 neurons was similarly reduced in both epileptic groups, young and aged animals. Therefore, our data suggest that the progressive reduction of m1 AChR expression in CA1 pyramidal cells of aged epileptic rats might bear relevance to the associated progressive cognitive impairment.
The purpose of the present study was to identify the changes in the levels of proinflammatory cytokines like IL-1β, IL-6 and TNF-α in peripheral circulation in Alzheimer’s disease (AD) subjects and to correlate these with associated depression and cognitive deficit. Fifty five AD subjects and thirty seven age and sex matched controls were included in the study. The AD patients were grouped as AD with depression (n= 31) and AD without depression (n= 24). The serum levels of IL-1β, IL-6 and TNF-α were determined by immunoassay by commercially available kits. The serum levels of IL-6 and TNF-α were elevated in AD patients with depression compared to control (p<0.001) or AD without depression (p<0.001). The serum level of IL-1β was higher in AD patients with or without depression as compared to controls. Furthermore, a strong inverse correlation was observed between the MMSE scores and serum levels of IL-6 or TNF-α in AD subjects with depression. The study highlights the important role of peripheral IL-6 and TNF-α in AD associated depression and cognitive deficits.
With an increased life expectancy in humans and thus an increase in the number of the elderly population, the frequency of hip fractures will rise as well. Aside from a higher incidence, hip fractures in a geriatric population is a significant problem due to the possible onset of severe and in some cases dramatic complications and consequences. The primary purpose of treatment and rehabilitation in the elderly after a hip fracture is to improve an individual’s quality of life. It is important to underline that principles and methods of functional restoration after hip fracture should consider careful planning of a rehabilitation program individually for every patient and its implementation with respect to decisions made by the rehabilitation team.
Aging is associated with declines in the neuromuscular and cardiovascular systems, resulting in an impaired capacity to perform daily activities. Frailty is an age-associated biological syndrome characterized by decreases in the biological functional reserve and resistance to stressors due to changes in several physiological systems, which puts older individuals at special risk of disability. To counteract the neuromuscular and cardiovascular declines associated with aging, as well as to prevent and treat the frailty syndrome, the strength and endurance training seems to be an effective strategy to improve muscle hypertrophy, strength and power output, as well as endurance performance. The first purpose of this review was discuss the neuromuscular adaptations to strength training, as well as the cardiovascular adaptations to endurance training in healthy and frail elderly subjects. In addition, the second purpose of this study was investigate the concurrent training adaptations in the elderly. Based on the results found, the combination of strength and endurance training (i.e., concurrent training) performed at moderate volume and moderate to high intensity in elderly populations is the most effective way to improve both neuromuscular and cardiorespiratory functions. Moreover, exercise interventions that include muscle power training should be prescribed to frail elderly in order to improve the overall physical status of this population and prevent disability.
Aging of biological systems occurs in spite of numerous complex pathways of maintenance, repair and defense. There are no gerontogenes which have the specific evolutionary function to cause aging. Although aging is the common cause of all age-related diseases, aging in itself cannot be considered a disease. This understanding of aging as a process should transform our approach towards interventions from developing illusory anti-aging treatments to developing realistic and practical methods for maintaining health throughout the lifespan. The concept of homeodynamic space can be a useful one in order to identify a set of measurable, evidence-based and demonstratable parameters of health, robustness and resilience. Age-induced health problems, for which there are no other clear-cut causative agents, may be better tackled by focusing on health mechanisms and their maintenance, rather than only disease management and treatment. Continuing the disease-oriented research and treatment approaches, as opposed to health-oriented and preventive strategies, are economically, socially and psychologically unsustainable.
Accumulating evidence has revealed that thePI3K/AKT/PTENpathway acts as a pivotal determinant of cell fate regarding senescence and apoptosis, which is mediated by intracellular reactive oxygen species (ROS) generation. NADPH oxidase (NOX) family of enzymes generates the ROS. The regulation of NOX enzymes is complex, with many members of this family exhibiting complexity in terms of subunit composition, cellular location, and tissue-specific expression. Cells are continuously exposed to the ROS, which represent mutagens and are thought to be a major contributor to several diseases including cancer and aging process. Therefore, cellular ROS sensing and metabolism are firmly regulated by a variety of proteins involved in the redox mechanism. In this review, the roles of oxidative stress in PI3K/AKT/PTEN signaling are summarized with a focus on the links between the pathways and NOX protein in several diseases including cancer and aging.
Uncontrolled continued exposure to oxidative stress is a precursor to many chronic diseases including cancer, diabetes, degenerative disorders and cardiovascular diseases. Of the many known mediators of oxidative stress, reactive oxygen species (ROS) and advanced glycation end products (AGEs) are the most studied. In the present review, we have summarized current data on the origin of circulating AGEs, discussed issues associated with reliable assessment of its steady state level, and changes in its level with age and select metabolic diseases. Lastly, we have made recommendations about life style changes that may decrease AGEs burden to promote healthy aging.
The heterogeneity of parameters is a ubiquitous biological phenomenon, with critical implications for biological systems functioning in normal and diseased states. We developed a method to estimate the level of objects set heterogeneity with reference to particular parameters and applied it to type II diabetes and heart disease, as examples of age-related systemic dysfunctions. The Friedman test was used to establish the existence of heterogeneity. The Newman-Keuls multiple comparison method was used to determine clusters. The normalized Shannon entropy was used to provide the quantitative evaluation of heterogeneity. There was obtained an estimate for the heterogeneity of the diagnostic parameters in healthy subjects, as well as in heart disease and type II diabetes patients, which was strongly related to their age. With aging, as with the diseases, the level of heterogeneity (entropy) was reduced, indicating a formal analogy between these phenomena. The similarity of the patterns in aging and disease suggested a kind of “early aging” of the diseased subjects, or alternatively a “disease-like” aging process, with reference to these particular parameters. The proposed method and its validation on the chronic age-related disease samples may support a way toward a formal mathematical relation between aging and chronic diseases and a formal definition of aging and disease, as determined by particular heterogeneity (entropy) changes.
Sarcopenia, an aging-induced generalized decrease in muscle mass, strength, and function, is known to affect elderly individuals by decreasing mobile function and increasing frailty and imbalance that lead to falls and fragile fractures. Sarcopenia is a known risk factor for osteoporotic fractures, infections, and early death in some specific situations. The number of patients with sarcopenia is estimated to increase to 500 million people in the year 2050. Sarcopenia is believed to be caused by multiple factors such as disuse, malnutrition, age-related cellular changes, apoptosis, and genetic predisposition; however, this remains to be determined. Various methods have been developed, but no safe or effective treatment has been found to date. This paper is a review on the association between sarcopenia and its related-fractures and their diagnoses and management methods to prevent fractures.
Degeneration of specific neuronal populations and progressive nervous system dysfunction characterize neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. These findings are also reported in inherited diseases such as phenylketonuria and glutaric aciduria type I. The involvement of mitochondrial dysfunction in these diseases was reported, elicited by genetic alterations, exogenous toxins or buildup of toxic metabolites. In this review we shall discuss some metabolic alterations related to the pathophysiology of diseases with neurological involvement and aging process. These findings may help identifying early disease biomarkers and lead to more effective therapies to improve the quality of life of the patients affected by these devastating illnesses.
Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.
The TOR (target of rapamycin) pathway has been convincingly shown to promote aging in various model organisms. In mice, inhibiting mTOR (mammalian TOR) by rapamycin treatment later in life can significantly extend lifespan and mitigate multiple age-related diseases. However, the underlying mechanisms are poorly understood. Cellular senescence is strongly correlated to organismal aging therefore providing an attractive model to examine the mechanisms by which mTOR inhibition contributes to longevity and delaying the onset of related diseases. In this review, we examine the connections between mTOR and cellular senescence and discuss how understanding cellular senescence on the aspect of mTOR signaling may help to fully appreciate its role in the organismal aging. We also highlight the opposing roles of senescence in various human diseases and discuss the caveats in interpreting the emerging experimental data.
Beside genetic and life-style characteristics environmental factors may profoundly influence mortality and life expectancy. The high altitude climate comprises a set of conditions bearing the potential of modifying morbidity and mortality of approximately 400 million people who are permanently residing at elevations above 1500 meters. However, epidemiological data on the effects of high altitude living on mortality from major diseases are inconsistent probably due to differences in ethnicity, behavioral factors and the complex interactions with environmental conditions. The available data indicate that residency at higher altitudes are associated with lower mortality from cardiovascular diseases, stroke and certain types of cancer. In contrast mortality from COPD and probably also from lower respiratory tract infections is rather elevated. It may be argued that moderate altitudes are more protective than high or even very high altitudes. Whereas living at higher elevations may frequently protect from development of diseases, it could adversely affect mortality when diseases progress. Corroborating and expanding these findings would be helpful for optimization of medical care and disease management in the aging residents of higher altitudes.
In recent decades, the increase in human longevity has made it increasingly important to expand our knowledge on aging. To accomplish this, the use of animal models is essential, with the most common being mouse (phylogenetically similar to humans, and a model with a long life expectancy) and Caenorhabditis elegans (an invertebrate with a short life span, but quite removed from us in evolutionary terms). However, some sort of model is needed to bridge the differences between those mentioned above, achieving a balance between phylogenetic distance and life span. Fish of the genus Nothobranchius were suggested 10 years ago as a possible alternative for the study of the aging process. In the meantime, numerous studies have been conducted at different levels: behavioral (including the study of the rest-activity rhythm), populational, histochemical, biochemical and genetic, among others, with very positive results. This review compiles what we know about Nothobranchius to date, and examines its future prospects as a true alternative to the classic models for studies on aging.
The HIV-infected older adult (HOA) community is particularly vulnerable to cognitive impairment. Previous studies in the general older adult population have reported that lower scores on tests of cognitive function often correlate negatively with aerobic fitness [5–7]. HIV-infected individuals have significantly reduced aerobic fitness and physical function compared to HIV-uninfected individuals. Determining important correlates of cognitive ability may be beneficial in not only detecting precursors to future cognitive impairments, but also target areas for interventions. The purpose of this study was to investigate the relationship between cognitive ability and aerobic fitness in HIV-infected older adults. We conducted a cross-sectional study of HOA on antiretroviral therapy (ART) >50 years of age. Domain specific cognitive function was assessed by means of a neuropsychological battery. Aerobic fitness (VO2peak) was assessed using a graded, progressive treadmill test. Thirty-seven HOA on ART (mean±SD: age 59±6 years, BMI 28±5, CD4 663±337 cells/ml, duration since HIV diagnosis 17±7 years; 81% males) completed the cognitive tests. Several domains of cognition were significantly associated with VO2peak by Spearman correlation analysis (p<0.05). By step-wise adjusted regression VO2peak was most frequently and significantly related to many cognitive domains such as verbal and visual memory, visual perception, and language (p<0.05). We found that participants with higher Vo2peak were less likely to have more severe forms of HIV-associated neurocognitive disorders (HAND) such as mild neurocognitive disorder (OR=0.65; p=0.01) and HIV-associated dementia (OR=0.64; p=0.0006). In HOA and in conclusion, aerobic fitness is related to cognitive performance on various tasks. The likelihood of cognitive impairment increased with lower fitness levels. Therefore, increased fitness may serve an important factor in maintenance of cognition and neural integrity for aging HIV-infected individuals. Future prospective and large scale studies are needed to evaluate the effect of fitness and vascular stiffness and function on cognition and brain structure among HOA.
Menopause is part of the aging process and is characterized by the natural cessation of menstruation; during this time, the production of ovarian hormones, especially estrogen, is sharply reduced. This reduction can cause symptoms and disorders that affect most women and can interfere with their quality of life. Women are also more susceptible to cardiovascular diseases during this period, considering that these ovarian hormones would be associated with a protective effect on the cardiovascular system, by acting at various levels, contributing to the body homeostasis. Among several effects on the cardiovascular system, the ovarian hormones seem to play an important role in the autonomic control of heart rate and blood pressure. A reduction in ovarian hormones causes an autonomic imbalance and increases the risk of cardiovascular diseases. In fact, this increased risk is justified by the key role the autonomic nervous system plays in all cardiac regulatory mechanisms, exerting a tonic and reflexive influence on the main variables of the cardiovascular system. The autonomic system controls various cardiovascular parameters, such as the modulation of heart rate and blood pressure, myocardial contractility and venous capacitance, directly participating in the regulation of cardiac output. Over the years, the standard treatment for menopause symptoms and disorders has been hormone replacement therapy (HRT). However, many studies have indicated the risks of HRT, which justify the need for new non-pharmacological therapies. To this end, physical training, mainly aerobic, has been applied with excellent results on the cardiovascular autonomic nervous system, as it reduces the risk of cardiac diseases and improves the survival rate with direct beneficial effects on the quality of life of these women during the aging process.
Depression is a common disease among young and older adults. Although it can be treated, non-adherence is very common among individuals of different ages. The aim of the present paper is to review and summarize research findings regarding depression among young and older adults, with a special focus on the phenomenon of treatment non-adherence among young and older adults with depression. The first section of the review focuses on describing the characteristics of depression in young and older adults. The second section focuses on treatment non-adherence of young and older adults, the prevalence of this phenomenon, and its consequences. The third section focuses on several factors (illness beliefs, treatment beliefs, self-stigma, and self-esteem) that were identified as having a significant association with treatment non-adherence of individuals with depression, with special attention focused on age differences. Results of the review of the literature reveal that research in the area of depression treatment non-adherence and its predictors among young and older adults has received, to date, very minor and limited attention. Thus, there is a need to expand the current body of knowledge and promote future interventions geared towards the unique characteristics of depression among young and older adults, in order to increase their treatment adherence.
A significant body of work, accumulated over the years, strongly suggests that damage in mitochondrial DNA (mtDNA) contributes to aging in humans. Contradictory results, however, are reported in the literature, with some studies failing to provide support to this hypothesis. With the purpose of further understanding the aging process, several models, among which mouse models, have been frequently used. Although important affinities are recognized between humans and mice, differences on what concerns physiological properties, disease pathogenesis as well as life-history exist between the two; the extent to which such differences limit the translation, from mice to humans, of insights on the association between mtDNA damage and aging remains to be established. In this paper we revise the studies that analyze the association between patterns of mtDNA damage and aging, investigating putative alterations in mtDNA copy number as well as accumulation of deletions and of point mutations. Reports from the literature do not allow the establishment of a clear association between mtDNA copy number and age, either in humans or in mice. Further analysis, using a wide spectrum of tissues and a high number of individuals would be necessary to elucidate this pattern. Likewise humans, mice demonstrated a clear pattern of age-dependent and tissue-specific accumulation of mtDNA deletions. Deletions increase with age, and the highest amount of deletions has been observed in brain tissues both in humans and mice. On the other hand, mtDNA point mutations accumulation has been clearly associated with age in humans, but not in mice. Although further studies, using the same methodologies and targeting a larger number of samples would be mandatory to draw definitive conclusions, the revision of the available data raises concerns on the ability of mouse models to mimic the mtDNA damage patterns of humans, a fact with implications not only for the study of the aging process, but also for investigations of other processes in which mtDNA dysfunction is a hallmark, such as neurodegeneration.
Aging is a multi-factorial process that ultimately induces a decline in our physiological functioning, causing a decreased health-span, quality of life and independence for older adults. Exercise participation is seen as a way to reduce the impact of aging through maintenance of physiological parameters. Eccentric exercise is a model that can be employed with older adults, due to the muscle’s ability to combine high muscle force production with a low energy cost. There may however be a risk of muscle damage before the muscle is able to adapt. The first part of this review describes the process of aging and how it reduces aerobic capacity, muscle strength and therefore functional mobility. The second part highlights eccentric exercise and the associated muscle damage, in addition to the repeated bout effect. The final section reviews eccentric exercise interventions that have been completed by older adults with a focus on the changes in functional mobility. In conclusion, eccentric endurance exercise is a potential training modality that can be applied to older adults for improving muscle strength, aerobic capacity and functional ability. However, further research is needed to assess the effects on aerobic capacity and the ideal prescription for eccentric endurance exercise.
Mitochondria are independent organelles with their own DNA. As a primary function, mitochondria produce the energy for the cell through Oxidative Phosphorylation (OXPHOS) in the Electron Transport Chain (ETC). One of the toxic products of this process is Reactive Oxygen Species (ROS), which can induce oxidative damage in macromolecules like lipids, proteins and DNA. Mitochondrial DNA (mtDNA) is less protected and has fewer reparation mechanisms than nuclear DNA (nDNA), and as such is more exposed to oxidative, mutation-inducing damage. This review analyzes the causes and consequences of mtDNA mutations and their relationship with the aging process. Neurodegenerative diseases, related with the aging, are consequences of mtDNA mutations resulting in a decrease in mitochondrial function. Also described are “mitochondrial diseases”, pathologies produced by mtDNA mutations and whose symptoms are related with mitochondrial dysfunction. Finally, mtDNA haplogroups are defined in this review; these groups are important for determination of geographical origin of an individual. Additionally, different haplogroups exhibit variably longevity and risk of certain diseases. mtDNA mutations in aging and haplogroups are of special interest to forensic science research. Therefore this review will help to clarify the key role of mtDNA mutations in these processes and support further research in this area.
Cardiovascular disease is one of the most common causes of death worldwide and the most usual in the western populations. Although it affects both sexes, it is more frequent in males in whom it shortens the average life expectancy. This difference has been attributed to the negative effects of testosterone; however, recent research showed that this hormone may have protective effects on the cardiovascular system. In confirmation to the above current evidence suggests that the low levels of testosterone could be associated with an increased CVD risk and with an augmentation of morbidity and mortality in males. In the present article, we present 2 cases of men with CVD and metastatic prostate cancer treated with bilateral orchiectomy who died of acute stroke during the perioperational period. The possible association of androgen deprivation with cardiovascular disease progression and the consequent risk of stroke are briefly discussed.
Unperturbed fetal development is essential for future health of an individual. Previous studies have linked diseases of aging to harmful alterations that happen during fetal development. Given the significant long-term impact that intrauterine environment has on an individual’s life, it was hypothesized that maternal stress during pregnancy will have negative effects on the offspring’s prenatal and postnatal growth. To test this, twenty-eight female and seven male Wistar rats (Rattus norvegicus) were purchased and bred to produce 176 offspring. During pregnancy, dams were randomly divided into four groups (n=7, per group) and immobilization stress induced as follows; Group 1 (GW1): immobilization stress on days 1–7 of pregnancy, Group 2 (GW2): on days 8–14, Group 3 (GW3): on days 15–21, Group 4 (Controls): left undisturbed. Maternal cortisol hormone, food intake, and weight gain were monitored during pregnancy. Pups were raised under normal laboratory conditions and sacrificed at ages: 4, 8, 12, and 16 weeks to determine the effect of prenatal stress. At necropsy, the tibia was removed and processed for histology. Differences among groups were determined by T-test or analysis of variance (ANOVA). Linear regression analysis was performed to establish the relationship between stress in utero and indicators of bone development in offspring. P values ≤ 0.05 were considered significant. Cortisol hormone levels in controls were lower than those of stressed animals. Stressed dams consumed 12.5% less food per day compared to controls. Animals in GW1 and GW2 gained less weight during pregnancy but had larger litters than did GW3 or the control group. Offspring born to GW3 were heavier compared to all other groups. GW3 offspring had a higher rate of bone formation. In conclusion, stress during pregnancy resulted in increased cortisol and reduced food intake in mothers, but faster growth and higher weight gain in offspring compared to controls.
Most human populations are undergoing a demographic transition regarding their age structure. This transition is reflected in chronic non-communicable diseases featuring among the main contributors to burden of disease. Considering that the aging process is a major risk factor for such conditions, understanding the mechanisms underlying aging and age-related diseases is critical to develop strategies to impact human health at population and/or individual-levels. Two different aspects of aging process (namely, telomere shortening and DNA damage accumulation) were shown to interact in positively impacting mice median survival. However, strategies aimed at translating such knowledge into actual human health benefits have not yet been discussed. In this manuscript, we present potential exposures that are suited for population-level interventions, and contextualize the roles of population (based on behavioral exposures) and individual-level (based on small-molecule administration) anti-aging interventions in different levels of disease prevention. We suggest that exposures such as moderate wine consumption, reducing calorie intake and active lifestyle are potentially useful for primordial and primary prevention, while small-molecules that activate telomerase and/or tumor suppression responses are more suited for secondary and tertiary prevention (although important for primary prevention in specific population subgroups). We also indicate the need of studying the impacts, on aging and age-related diseases, of different combinations of these exposures in well-conducted randomized controlled trials, and propose Mendelian randomization as a valuable alternative to gather information in human populations regarding the effects of potential anti-aging interventions.