Stratum corneum hydration inversely correlates with certain serum cytokine levels in the elderly,possibly contributing to inflammaging

The equine population in the United States and worldwide now includes a higher percentage of geriatric horses than ever previously recorded, and as methods to treat and manage elderly equids are developed and refined, this aging population will likely continue to expand. A better understanding of how horses age and the effect of age on immunity and disease susceptibility is needed to enable targeted preventative healthcare strategies for aged horses. This review article outlines the current state of knowledge regarding the effect of aging on immunity, vaccine responsiveness, and disease risk in the horse, highlighting similarities and differences to what is observed in aged humans. Horses show similar but milder age-related alterations in immune function to those reported in people. Decreases in lymphocyte proliferation and antibody production and diminished response to vaccination have all been documented in elderly horses, however, increased risk of infectious disease is not commonly reported. Aged horses also show evidence of a proinflammatory state (inflammaging) yet appear less susceptible to the chronic diseases of people for which inflammation is a risk factor. Information is currently lacking as to why the horse does not experience the same risk of age-related disease (e.g., cancer, heart disease, neurodegeneration) as people, although a lack of negative lifestyle habits, differences in diet, exercise, genetics and physiology may all contribute to improved health outcomes in the older horse.

     

Obesity is a common soil for premature cardiac aging and heart diseases - Role of autophagy

The advance in medical technology and healthcare has dramatically improved the average human lifespan. One of the consequences for longevity is the high prevalence of aging-related chronic disorders such as cardiovascular diseases, cancer and metabolic abnormalities. As the composition of aging population is raising in western countries, heart failure remains the number one cause of death with a more severe impact in the elderly. Obesity and aging are the most critical risk factors for increased susceptibility to heart failure in developing and developed countries. Numerous population-based and experimental data have depicted a close relationship between the age-related diseases and obesity. There is an overall agreement that obesity is causally linked to the development of cardiovascular disorders and severe premature cardiac aging. Accumulating evidence indicates that autophagy plays an important role in obesity, cardiac aging and diseases. In this review, we will focus on the role of autophagy in obesity-related cardiac aging and diseases, and how it regulates age-dependent changes in the heart.     

Spontaneous heart disease in the adult chimpanzee (Pan troglodytes)

Background  A high incidence of heart disease, especially idiopathic cardiomyopathy (IC), is seen in chimpanzees ( Pan troglodytes ).
Methods  We reviewed clinical records and necropsy reports of 87 adult chimpanzees for possible causes of heart disease/IC. We examined age, sex, cause of death, weight, diet, environment, infectious diseases, experimental uses and clinical pathology.
Results  The overall prevalence of heart disease in chimpanzees was 67.81%; the prevalence of IC was 51.72%. The prevalence of IC was significantly higher in males (60.32%) than that in females (29.17%, P  = 0.009). The prevalence of other heart disease was higher in females (25%) than that in males (12.70%, P  = 0.165). Heart failure occurred in 47.13% of chimpanzees. Heart disease was the primary cause of death in 34.49% of chimpanzees; 29.88% died of unknown causes.
Conclusions  We found no evidence that diet, environment, viral agents, experimental use or disease exposure contributed to the deaths resulting from IC in chimpanzees.     

Modulating human aging and age-associated diseases

Population aging is progressing rapidly in many industrialized countries. The United States population aged 65 and over is expected to double in size within the next 25 years. In sedentary people eating Western diets aging is associated with the development of serious chronic diseases, including type 2 diabetes mellitus, cancer and cardiovascular diseases. About 80% of adults over 65 years of age have at least one chronic disease, and 50% have at least two chronic diseases. These chronic diseases are the most important cause of illness and mortality burden, and they have become the leading driver of healthcare costs, constituting an important burden for our society. Data from epidemiological studies and clinical trials indicate that many age-associated chronic diseases can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. Several recent studies suggest that more drastic interventions (i.e. calorie restriction without malnutrition and moderate protein restriction with adequate nutrition) may have additional beneficial effects on several metabolic and hormonal factors that are implicated in the biology of aging itself. Additional studies are needed to understand the complex interactions of factors that regulate aging and age-associated chronic disease.     

Hypertension Increases With Aging and Obesity in Chimpanzees (Pan troglodytes)

Cardiovascular disease is a primary cause of morbidity and mortality in captive chimpanzees. Four years of blood pressure (BP) data were analyzed from a captive former laboratory population of 201 healthy adult chimpanzees with assessment of age and obesity on elevated BP. Five different measures of obesity were compared: abdominal girth, basal metabolic rate, body‐mass index (BMI), body weight, and surface area. Systolic BP varied by sex. Obesity did not influence male BP. For females, obesity was a significant determinant of BP. The best measure of female obesity was basal metabolic rate and the worst was BMI. Median systolic BP of healthy weight females (<54.5 kg) was significantly lower (128 mmHg) than overweight or obese females (140 mmHg), but both were lower than all males (147 mmHg). For diastolic BP, neither sex nor any of the five obesity measures was significant. But age was highly significant, with geriatric chimpanzees (>30 years) having higher median diastolic BP (74 mmHg) than young adults of 10–29 years of age (65 mmHg). By these criteria, 80% of this population is normotensive, 7% prehypertensive, and 13% hypertensive. In summary, systolic BP intervals required adjustment for obesity among females but not males. Diastolic BP required adjustment for advanced age (≥30 years). Use of these reference intervals can facilitate timely clinical care of captive chimpanzees. Zoo Biol. 32:79‐87, 2013. © 2012 Wiley Periodicals, Inc.     

Effects of aging on hematology and serum clinical chemistry in chimpanzees (Pan troglodytes)

A number of age-related changes in physiological functions have been identified in macaques and humans. However, few studies have examined physiological aging in chimpanzees, despite the increasing age of the chimpanzee population. We documented age-related changes in seven hematology and 17 clinical chemistry parameters in 49 adult chimpanzees (17 males, 32 females) as a comparative viewpoint with human and macaque aging. Longitudinal data were analyzed using weighted linear and quadratic mixed effects regression models. Male chimpanzees exhibited a significant age-related increase in anemia risk, based on significant decreases in hemoglobin (F(1,49)=12.45, P=0.0009) and hematocrit (F(1,49)=15.42, P=0.0003). Both sexes exhibited significant age-related decreases in both kidney and liver function. Decreases in kidney function were noted by significant increases in blood urea nitrogen (F(1,45)=3.92, P=0.036) and creatinine (F(1,50)=5.63, P=0.022) as well as changes in electrolyte (i.e., sodium, potassium, phosphorous, chloride) balance. Declining liver function was based on significant increases in globulin (F(1,46)=32.34, P<0.0001) and decreases in albumin (F(1,48)=23.42, P<0.0001). These changes were most evident beginning at 25-30 years of age in males and 30-35 years of age in females. We recommend amending chimpanzee age classes to categorize males over 25 years and females over 30 years as aged.     

Burden and Correlates of Geriatric Depression in the Uyghur Elderly Population,Observation from Xinjiang,China

Background

With the gradual aging of the population, geriatric depression has become a major public health issue in China owing to its overall upward trend and associated negative socio-economic impact. Dearth of information regarding the burden and correlates of geriatric depression among Uyghur minority population in Xinjiang Autonomous Region, called for a comprehensive survey involving representative sample for designing efficient targeted intervention to control this disabling disease.

Methods

A cross-sectional study was conducted among 1329 consenting Uyghur elderly in 2011 in six randomly selected communities/villages in Xinjiang. Information about socio-demographics, behavior, negative life-events, satisfaction regarding income/quality of life and other chronic diseases were collected while assessment of geriatric depression was done using Geriatric Mental State Schedule (GMS).

Results

Among these participants, majority were currently married, had attended elementary school or less, had an average annual family income of less than 3000 Yuan/person, had strong religious beliefs while 10.61% (2.77% in urban and 23.60% in rural area) had geriatric depression (5.91% among male and 14.58% among females). 61.83% were suffering from other chronic diseases, 96.16% could take care of themselves and 39.28% had experienced negative events during last two years. Religious belief (AOR = 3.92, 95% CI 1.18–13.03), satisfaction regarding quality of life (AOR = 0.53, 95% CI 0.37–0.84) and income (AOR = 0.75, 95% CI 0.35–1.60), suffering from more chronic diseases (AOR = 1.70, 95% CI 1.42–2.04), experiencing three or more negative events (AOR = 1.72, 95% CI 0.92–3.22) and lack of ability to take self-care (AOR = 2.20, 95% CI 1.09–4.48) were all associated with having geriatric depression with or without adjustment for gender, education and occupation.

Conclusion

High prevalence of geriatric depression among Uyghur elderly in Xinjiang seemed to call for urgent interventions, specifically targeting rural residents, who experienced more negative life-events, were suffering from chronic diseases and were dissatisfied with their income and quality of life.     

Association between morbidity and skeletal biomarkers of biological aging

The Osseographic Scoring System (OSS) is a synthetic measure of skeletal aging that combines osteoporotic and osteoarthritic changes of the hand. The OSS is used to evaluate biological age in a population. The aim of the present study was to evaluate the association between certain chronic morbidities and the skeletal biomarker of biological aging. We performed a population-based study on a large sample of individuals who were receiving no medications to treat or prevent chronic morbidities [668 male (age 18-89 years) and 608 female (age 18-81 years) Chuvashians]. Morbidity data obtained from the individuals' medical records was sorted into 16 categories. A one-way ANOVA was used to elucidate the association between morbidity and age-adjusted OSS score. Statistically significant differences between means of OSS scores in affected vs. nonaffected individuals were found in the rheumatic diseases group. Ischemic heart disease, pulmonary diseases, traumatic brain injuries, and gynecological diseases also showed differences; however, after correction for multiple testing, the results were statistically nonsignificant. We conclude that individuals who suffer from the mentioned chronic morbidities will show a higher degree of skeletal aging. Further research is needed to clarify the biological mechanisms of association between certain types of morbidities and changes in skeletal aging.     

Aging, cancer, and cancer vaccines

ABSTRACT: World population has experienced continuous growth since 1400 A.D. Current projections show a continued increase - but a steady decline in the population growth rate - with the number expected to reach between 8 and 10.5 billion people within 40 years. The elderly population is rapidly rising: in 1950 there were 205 million people aged 60 or older, while in 2000 there were 606 million. By 2050, the global population aged 60 or over is projected to expand by more than three times, reaching nearly 2 billion people 1. Most cancers are age-related diseases: in the US, 50% of all malignancies occur in people aged 65-95. 60% of all cancers are expected to be diagnosed in elderly patients by 2020 2. Further, cancer-related mortality increases with age: 70% of all malignancy-related deaths are registered in people aged 65 years or older 3. Here we introduce the microscopic aspects of aging, the pro-inflammatory phenotype of the elderly, and the changes related to immunosenescence. Then we deal with cancer disease and its development, the difficulty of treatment administration in the geriatric population, and the importance of a comprehensive geriatric assessment. Finally, we aim to analyze the complex interactions of aging with cancer and cancer vaccinology, and the importance of this last approach as a complementary therapy to different levels of prevention and treatment. Cancer vaccines, in fact, should at present be recommended in association to a stronger cancer prevention and conventional therapies (surgery, chemotherapy, radiation therapy), both for curative and palliative intent, in order to reduce morbidity and mortality associated to cancer progression.     

The implementation and initial evaluation of a physical therapy program for captive chimpanzees (Pan troglodytes)

Due to advances in captive nonhuman primate (NHP) medical care, the number of geriatric chimpanzees (≥35-years old) is growing. With old age comes a variety of physical conditions, including arthritis, stroke, and mobility impairments. Programs aimed at enhancing the welfare of geriatric chimpanzees are now quite common, but there are few published empirical evaluations of the efficacy of such programs. The current study aimed to create, implement, and evaluate the effects of participation in a physical therapy (PT) program on physical health, mobility, welfare, and behavior. Nine chimpanzees with mobility impairments participated in personalized PT routines (using positive reinforcement training) twice per week for 5 months. Additionally, nine control chimpanzees (non-mobility-impaired, matched with PT chimpanzees on age and gender) participated in body exam behavior sessions (also using positive reinforcement training) twice per week. All chimpanzees were rated on 14 health, well-being, and behavior items, as well as level of mobility throughout the PT program. Chimpanzees that participated in the PT program showed significant increases in ratings of physical health, well-being, and activity levels across phases of the program. Furthermore, compared to control chimpanzees, PT chimpanzees showed significant increases in ratings of ease of movement. Because raters were not blind to physical therapy treatment, our results represent an initial evaluation of the program that may suggest that participation in the PT program has physical, behavioral, and welfare benefits. Assessments of novel geriatric-focused care strategies and programs are essential to further enhance the welfare of the captive chimpanzee population, which is currently comprised of many geriatric animals, whose proportion of the captive population will only increase.     

Epidemiology,risk factors across the spectrum of age-related metabolic diseases

BackgroundPopulation aging is dynamic process of increasing proportion of older adults in the total population, which is an inescapable result of decline in fertility rate and extension in life expectancy. Inevitably, age-related metabolic diseases, for example obesity, type 2 diabetes, metabolic syndrome, dyslipidemia, and nonalcoholic fatty liver disease, are becoming epidemic globally along with the demographic transition.ContentThe review examines the literatures related to: 1) the epidemiology of age related metabolic diseases including obesity, type 2 diabetes, metabolic syndrome, dyslipidemia, and nonalcoholic fatty liver disease; and 2) the risk factors of age related metabolic diseases including genetic factors, diet, smoking, Physical activity, intestinal microbiota and environmental factors.ConclusionPopulation aging is becoming epidemic worldwide, resulting in increasing incidence and prevalence of a serious of age-related metabolic diseases. Both genetic and environmental factors contribute to the diseases, thus interventions targeting on these factors may have beneficial effect on the development of age-related metabolic diseases.     

Age-related changes in urinary testosterone levels suggest differences in puberty onset and divergent life history strategies in bonobos and chimpanzees

Research on age-related changes in morphology, social behavior, and cognition suggests that the development of bonobos (Pan paniscus) is delayed in comparison to chimpanzees (Pan troglodytes). However, there is also evidence for earlier reproductive maturation in bonobos. Since developmental changes such as reproductive maturation are induced by a number of endocrine processes, changes in hormone levels are indicators of different developmental stages. Age-related changes in testosterone excretion are an indirect marker for the onset of puberty in human and non-human primates. In this study we investigated patterns of urinary testosterone levels in male and female bonobos and chimpanzees to determine the onset of puberty. In contrast to other studies, we found that both species experience age-related changes in urinary testosterone levels. Older individuals of both sexes had significantly higher urinary testosterone levels than younger individuals, indicating that bonobos and chimpanzees experience juvenile pause. The males of both species showed a similar pattern of age-related changes in urinary testosterone levels, with a sharp increase in levels around the age of eight years. This suggests that species-differences in aggression and male mate competition evolved independently of developmental changes in testosterone levels. Females showed a similar pattern of age-related urinary testosterone increase. However, in female bonobos the onset was about three years earlier than in female chimpanzees. The earlier rise of urinary testosterone levels in female bonobos is in line with reports of their younger age of dispersal, and suggests that female bonobos experience puberty at a younger age than female chimpanzees.     

Evidence for aging theories from the study of a hunter—gatherer people (Ache of Paraguay)

In the late seventies, a small tribal population of Paraguay, the Ache, living under natural conditions, was studied. Data from this population turn out to be useful for considerations about evolutionary hypotheses on the aging phenomenon. 1) Ache show an age-related increasing mortality, which strongly limits the mean duration of life, as observed in other studies on mammal and bird species. 2) According to current theories on aging, in the wild very few or no individual reach old age and, so, aging cannot be directly influenced by natural selection. However, data from our population show that a significant proportion of the population reaches in the wild 60 and 70 years of age. 3) Data from Ache are also in agreement with the observation about an inverse correlation between extrinsic mortality and deaths due to the age-related increasing mortality. 4) For many gerontologists, the age-related decline of vital functions is a consequence of the gradual decline of cell turnover, genetically determined and regulated by the declining duplication capacities of stem cells. The current interpretation is that these restrictions are a general defense against the proliferation of any tumoral mass. However, among wild Ache cancer is virtually unknown in non-elderly subjects, and only among older individuals are there deaths attributable to oncological diseases. Moreover, fitness decline begins long before oncological diseases have fatal effects in significant numbers. This completely disproves the current hypothesis, because a supposed defense against a deadly disease cannot exterminate a population before the disease begins to kill. These data are consistent with similar data from other species studied under natural conditions, and they bring new arguments against the non-adaptive interpretation of aging and in support of the adaptive interpretation.     

Successful treatment of idiopathic dilated cardiomyopathy in an adult chimpanzee (Pan troglodytes)

Various congenital and acquired forms of heart disease have been reported in captive lowland gorillas, and heart disease is a major cause of morbidity and mortality in geriatric humans. However, the prevalence of heart disease is unknown in nonhuman great apes species. Indeed, little is known about heart disease in chimpanzees, although the species has been used in research for decades. This report details the clinical presentation and diagnostics (thoracic radiography, electrocardiography, and echocardiography) utilized to diagnose idiopathic dilated cardiomyopathy in a 27-year-old male chimpanzee. Treatment decisions--indicated by follow-up diagnostics including repeat electrocardiography, echocardiography, and clinical laboratory data--over the 22-month period during which he continues to be treated are described. In addition, electrocardiographic and echocardiographic findings obtained from 20 clinically normal adult (11 female and 9 male) chimpanzees are presented for comparison.     

Hsp90 inhibitors as senolytic drugs to extend healthy aging

Aging is characterized by progressive decay of biological systems and although it is not considered a disease, it is one of the main risk factors for chronic diseases and many types of cancers. The accumulation of senescent cells in various tissues is thought to be a major factor contributing to aging and age-related diseases. Removal of senescent cells during aging by either genetic or therapeutic methods have led to an improvement of several age related disease in mice. In this preview, we highlight the significance of developing senotherapeutic approaches to specifically kill senescent cells (senolytics) or suppress the senescence-associated secretory phenotype (SASP) that drives sterile inflammation (senomorphics) associated with aging to extend healthspan and potentially lifespan. Also, we provide an overview of the senotherapeutic drugs identified to date. In particular, we discuss and expand upon the recent identification of inhibitors of the HSP90 co-chaperone as a new class of senolytics.     

Is There a Molecular Logic That Sustains Neuronal Functional Integrity and Survival? Lipid Signaling Is Necessary for Neuroprotective Neuronal Transcriptional Programs

A challenge to civilization is the growing incidence in the loss of sight and cognition due to increased life expectancy. Therefore, we are confronted with a rise in the occurrence of photoreceptor- and neuronal-survival failure, as reflected mainly by age-related macular degeneration (AMD) and Alzheimer’s disease (AD). Nervous system development is driven by neuronal apoptotic cell death, and thereafter, for the entire lifespan of an organism, neurons are postmitotic cells. In neurodegenerative diseases, apoptosis and other forms of cells death lead to selective neuronal loss. Although age is the main risk factor, not everyone develops these diseases during aging. Despite decades of important findings about neuronal cell death, the specific mechanisms that regulate neuronal survival remain incompletely understood.     

A common mutation of the MYH gene is associated with increased DNA oxidation and age-related diseases

We describe a common mutation of the MYH gene, which is involved in the repair of oxidative damage to DNA, and its relationship to age, levels of 8-OHdG, and circulating levels of interleukin-1. We studied 1146 “healthy” and 562 unselected Chinese subjects. We observed a reverse insertion of the AluYb8 sequence (AluYb8MYH) to be homozygous in ～25.8% of the healthy Chinese population age 20–29 years, with the incidence of homozygosity decreasing to 15.7% by age 50–59 years. Because subjects were selected on the basis of absence of disease during medical screening, this suggests that homozygosity for this gene has a marked impact on the development of age-related or chronic diseases or mortality. Because the MYH gene is involved in DNA repair we assessed whether homozygous carriage of this gene was associated with increased levels of 8-OHdG in the leukocytic DNA of carriers. The level of 8-OHdG increased from 3.8 8-OHdG/10⁶ dG in wild-type carriers to 10.8 8-OHdG/10⁶ dG in homozygous carriers, suggesting that the presence of the mutation was associated with impaired DNA repair. Because this mutation might be associated with the increased development of age-related or chronic disease and inflammation, we also measured plasma concentrations of interleukin-1, which increases with aging and chronic disease. We observed a highly significant increase in plasma interleukin-1 in patients homozygous for the AluYb8 insertion in the MYH gene consistent with accelerated aging or development of undiagnosed disease in homozygous subjects. Screening for this genetic variation may have predictive value in assessing potential longevity of subjects in China, as well as in the Western world.     

Genetically engineered mice and their use in aging research

Genetically engineered animal models have been and will continue to be invaluable for exploring the basic mechanisms involved in the aging process as well as in extending our understanding of diseases found to be more prevalent in the older human population. Continued development of such in vivo systems will allow scientists to further dissect the role genetic and environmental factors play in aging and in age-related disease states and to enhance our understanding of these processes. In this article we discuss techniques involved in the development of such models and review some examples of laboratory mouse strains that have been used to study either normal aging or select diseases associated with aging.