Late onset is a key unifying feature of human neurodegenerative maladies such as Alzheimer’s and Parkinson’s diseases and prion disorders. While sporadic cases typically emerge during the patient’s seventh decade of life or later, mutation-linked, familial cases manifest during the fifth or sixth decade. This common temporal emergence pattern raises the prospect that slowing aging may prevent the accumulation of toxic protein aggregates that lead to the development of these disorders, postpone the onset of these maladies, and alleviate their symptoms once emerged. Invertebrate-based studies indicated that reducing the activity of insulin/IGF signaling (IIS), a prominent aging regulatory pathway, protects from neurodegeneration-linked toxic protein aggregation. The validity of this approach has been tested and confirmed in mammals as reducing the activity of the IGF-1 signaling pathway protected Alzheimer’s model mice from the behavioral and biochemical impairments associated with the disease. Here I review the recent advances in the field, describe the known mechanistic links between toxic protein aggregation and the aging process, and delineate the future therapeutic potential of IIS reduction as a treatment for various neurodegenerative disorders.
The term sarcopenia describes the loss of skeletal muscle mass, strength, and function in old age. As the world population continues to grow older, more attention is given to the phenomena of sarcopenia and the search for strategies of prevention and treatment. The progression of sarcopenia is affected by age-related physiological and systemic changes in the body, including alterations in skeletal muscle tissue, hormonal changes, increased inflammatory activities, and oxidative stress. Sarcopenia progression is also affected by lifestyle factors which are far more controllable. These factors include various aspects of nutrition, physical activity, exercise, alcohol intake, and tobacco use. Raising the public awareness regarding the impact of these factors, as causes of sarcopenia and potential strategies of prevention and treatment, is of great importance. In this review we aim to describe various lifestyle factors that affect the etiology, prevention, and treatment of sarcopenia.
Life expectancy has been increasing in the last few decades in the Western world and is accompanied by higher occurrence of age-related diseases like metabolic, cardiovascular, and renal diseases and also with a decline in immune functions. In HIV-infected people, due to the use of combination antiretroviral therapy cART, life expectancy has increased. As a result, non-AIDS conditions which are age-associated have become more prevalent and appear earlier, resulting in accelerated aging in HIV patients. These non-AIDS conditions in HIV patients are associated with CD4+ T cell counts: lower counts are associated with higher rates of liver, cardiovascular, renal, and neurocognitive disorders. The effect of viral load and cART on the earlier occurrence of age-associated diseases is less significant than the CD4 count effect. Thus, the loss of immune functions in HIV-infected patients may enhance aging.
The oldest-old are the fastest growing segment of the Western population. Over half of the oldest-old will have dementia, but the etiology is yet unknown. Age is the only risk factor consistently associated with dementia in the oldest-old. Many of the risk and protective factors for dementia in the young elderly, such as ApoE genotype, physical activity, and healthy lifestyle, are not relevant for the oldest-old. Neuropathology is abundant in the oldest-old brains, but specific pathologies of Alzheimer’s disease (AD) or vascular dementia are not necessarily correlated with cognition, as in younger persons. It has been suggested that accumulation of both AD-like and vascular pathologies, loss of synaptic proteins, and neuronal loss contribute to the cognitive decline observed in the oldest-old. Several characteristics of the oldest-old may confound the diagnosis of dementia in this age group. A gradual age-related cognitive decline, particularly in executive function and mental speed, is evident even in non-demented oldest-old. Hearing and vision losses, which are also prevalent in the oldest-old and found in some cases to precede/predict cognitive decline, may mechanically interfere in neuropsychological evaluations. Difficulties in carrying out every-day activities, observed in the majority of the oldest-old, may be the result of motor or physical dysfunction and of neurodegenerative processes. The oldest-old appear to be a select population, who escapes major illnesses or delays their onset and duration toward the end of life. Dementia in the oldest-old may be manifested when a substantial amount of pathology isaccumulated, or with a composition of a variety of pathologies. Investigating the clinical and pathological features of dementia in the oldest-old is of great importance in order to develop therapeutic strategies and to provide the most elderly of our population with good quality of life.
Genetic determinants of sex in placental mammals developed by the evolution of primordial autosomes into the male and female sex chromosomes. The Y chromosome determines maleness by the action of the gene SRY, which encodes a protein that initiates a sequence of events prompting the embryonic gonads to develop into testes. The X chromosome in the absence of a Y chromosome results in a female by permitting the conversion of the embryonic gonads into ovaries. We trace the historical progress that resulted in the discovery that one X chromosome in the female is randomly inactivated in early embryogenesis, accomplishing approximate equivalency of X chromosome gene dosage in both sexes. This event results in half of the somatic cells in a tissue containing proteins encoded by the genes of the maternal X chromosome and half having proteins encoded by the genes of the paternal X chromosome, on average, accounting for the phenotype of a female heterozygote with an X chromosome mutation. The hypothesis of X chromosome inactivation as a random event early in embryogenesis was first described as a result of studies of variegated coat color in female mice. Similar results were found in women using the X chromosome-linked gene, glucose-6-phosphate dehydrogenase, studied in red cells. The random inactivation of the X chromosome-bearing genes for isoenzyme types A and B of glucose-6-phosphate dehydrogenase was used to establish the clonal origin of neoplasms in informative women with leiomyomas. Behind these discoveries are the stories of the men and women scientists whose research enlightened these aspects of X chromosome function and their implication for medicine.
Among the wide-spectrum contribution of the Rambam – the Maimonides – in philosophy to the word and to Judaism are his ideas on the body and on the soul and on the relations between them. His major approaches in these subjects are the following: 1) The body is the home of the soul, and the soul guides the body. That means the body and the soul are one unit. 2) The soul has five virtual parts. Each part is responsible for another activity in the human being. 3) Except for the treatment of diseases of the body and the soul with drugs, foods, physical exercise, etc., the Rambam believes that maintaining the health – of the body and of the soul – lies first of all, and probably exclusively, in observing the commandments and improving one’s ways, morals and conduct up to their highest levels, toward all of the world’s creatures. 4) The Rambam is of the opinion that one needs to persist in learning the Torah. One should worship God with awe and love and observe good values and virtues. All of these build the frameworks that maintain mental health and strengthen man’s abilities to develop skills for maintaining bodily health. This is so because body and soul are one – which is the basis of the Rambam’s philosophy of health and medicine.
Epidemiologic studies now strongly support the hypothesis, proposed over 2 decades ago , that developmental programming of the kidney impacts an individual’s risk for hypertension and renal disease in later life. Low birth weight is the strongest current clinical surrogate marker for an adverse intrauterine environment, and based on animal and human studies, is associated with a low nephron number. Other clinical correlates of low nephron number include female gender, short adult stature, small kidney size and prematurity. Low nephron number in Caucasian and Australian Aboriginal subjects has been shown to be associated with higher blood pressures, and conversely, hypertension is less prevalent in individuals with higher nephron numbers. In addition to nephron number, other programmed factors associated with the increased risk of hypertension include salt-sensitivity, altered expression of renal sodium transporters, altered vascular reactivity and sympathetic nervous system overactivity. Glomerular volume is universally found to vary inversely with nephron number, suggesting a degree of compensatory hypertrophy and hyperfunction in the setting of a low nephron number. This adaptation may become overwhelmed in the setting of superimposed renal insults e.g. diabetes mellitus, or rapid catch-up growth, leading to the vicious cycle of ongoing hyperfiltration, proteinuria, nephron loss and progressive renal functional decline. Many millions of babies are born with low birth weight every year, hypertension and renal disease prevalences are increasing around the globe. At present, little can be done clinically to augment nephron number; therefore adequate pre-natal care and careful post-natal nutrition are crucial to optimize an individual’s nephron number during development, and potentially to stem the tide of the growing cardiovascular and renal disease epidemics world-wide.
Objective. To understand high-performing front-line employees’ values as reflected in their narratives of day-to-day interactions in a large health care organization.
Methods. A total of 150 employees representing various roles within the organization were interviewed and asked to share work-life narratives (WLNs) about value-affirming situations (i.e. situations in which they believed their actions to be fully aligned with their values) and value-challenging situations (i.e. when their actions or the actions of others were not consistent with their values), using methods based on appreciative inquiry.
Results. The analysis revealed 10 broad values. Most of the value-affirming WLNs were about the story-teller and team providing care for the patient/family. Half of the value-challenging WLNs were about the story-teller or a patient and barriers created by the organization, supervisor, or physician. Almost half of these focused on “treating others with dis/respect”. Only 15% of the value-challenging WLNs contained a resolution reached by the participants, often leaving them describing unresolved and frequently negative feelings.
Conclusions. Appreciative inquiry and thematic analysis methods were found to be an effective tool for understanding the important and sometimes competing role personal and institutional values play in day-to-day work. There is remarkable potential in using WLNs as a way to surface and reinforce shared values and, perhaps more importantly, respectfully to identify and discuss conflicting personal and professional values.
We review three decades of unsuccessful efforts by public policy-makers in the United States to develop programs to lower the rate of preterm birth. We analyze why these efforts had been unsuccessful. Finally, we will speculate about whether something has changed in the last few years that might finally bend the curve and reverse the trend of a steadily rising preterm birth rate.
As more reports emerge of improved mortality and morbidity rates in infants born at the edge of viability, there may be need to reassess protocols and recommendations that encourage only comfort care for infants who are born at less than 24 weeks’ gestation. Analysis of those studies that report extremely poor survival of these infants reveals that, all too often, the results are measures of a self-fulfilling prophesy that reflects a predetermined non-aggressive global policy of no resuscitation and minimal investment in intensive care. Furthermore, little distinction is made between high- and low-risk infants of the same gestational age despite repeated studies that indicate that one can identify - subpopulations that have as much as a 20-50% increased chance of surviving with little if any long-term neurodevelopmental impairment. Thus, the need to reassess current policies is discussed.
