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.
Age as a risk for diseases: We offer a different approach to delaying or preventing age-related diseases. To understand the necessity for a new approach we have plotted the mortality rates in Israelis in relation to specific age groups and diseases...(Click below to read the entire editorial.)
The sirtuins are highly conserved enzyme homologues of the yeast Sir2, with activities of NAD+ dependent deacetylase and/or mono ADP ribosyltransferase. A long line of evidence has implicated sirtuins in regulating the aging process of yeast, worms, flies, and rodents. Moreover, much work has been published on the important role of sirtuins in several age-related diseases such as diabetes type II, cancer, cardio¬vascular diseases, and dyslipidemia. However, despite the many publications supporting a pro-longevity role for sirtuins, there has been emerging debate about the direct role of Caenorhabditis elegans and Drosophila melanogaster sirtuins in aging and in lifespan extension in response to dietary restriction. In addition, until recently, the role of the seven mammalian sirtuins, SIRT1 to SIRT7, in regulating lifespan was unclear. Here, we review the history of the scientific debate on the role of sirtuins in regulating lifespan, especially in light of a recent publication showing a direct regulation of mammalian lifespan by a sirtuin family member, SIRT6.
The immune system is critical for protection and health maintenance and is likely required for a long lifespan. Yet, despite its importance for health, the ability to assess its quality of function has been poor, nor is much known on its variation between individuals. Hence direct assessment of immune health has largely been missing from medicine, and metrics of immune health are not well defined, especially in non-extreme states. This is chiefly due to the high complexity of the immune system. Recently emerging technologies now enable broad surveying of many immune system components at high resolution, setting forth a transformation of immunology and, through it, medicine. Such technologies enable, for the first time, high resolution monitoring of an individual’s immune system. The resulting information can be used for diagnostic and prognostic purposes, as well as to provide a quantitative, global view of the immune system, i.e. ‘systems immunology.’ This is especially relevant in the context of aging, in which the immune system exhibits profound alterations in state and function.
For patients with acute coronary syndrome (ACS), the first priority is to alert emergency services. In addition to an ECG (ideally taken during the first medical contact at the patient’s home), the key of live saving is the immediate antithrombotic therapy with acetylsalicylic acid (ASA) and (unless contraindicated) an injection of unfractionated heparin or bivalirudin as an alternative anticoagulant. Dual antiplatelet therapy (ASA combined with other antiplatelet drugs, like thienopyridines) should be started as soon as possible in the ambulance or at the latest in the hospital. For clopidogrel, a loading dose of 600 mg is the standard. To avoid the risk of an unknown low or missing clopidogrel-response, prasugrel is recommended instead, administrating a loading dose of 60 mg, if no contraindication (s/p stroke or TIA) exists. When PCI is planned, the ambulance must head directly to the nearest hospital with continuous (24/7) PCI service within 90 (to 120) minutes. The maintenance dose for clopidogrel is 75 mg/d; a daily double-dose has not proven to be superior, even in “low responders”. For prasugrel, the maintenance dose is usually 10 mg/d. To avoid bleeding complications in patients ≥75 y and/or <60 kg, a prasugrel maintenance dose of 5 mg/d is recommended. The ESC guidelines recommend DAPT for 1 year after ACS – independent of the type of ACS and independent of whether any or which coronary stent has been implanted. With DAPT, the patient – and not the stent – is treated.
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.
Successful deceased organ donation requires a reproducible—consistent (scientific) system that eva-luates the potential for organ donation and determines objectively whether the national system is achieving its goals. The science of organ donation also pertains to the determination of death. We are a common humanity that dies similarly— a humanity whose ultimate criterion of life resides in the function of the human brain. The recent brain death law of Israel encouragingly enables a determination of death by the loss of neurologic function but it has become complicated by a practice that may perpetuate societal misperceptions. As a result opportunities for deceased organ donation --to provide for Israelis in need of organ transplants are being lost. A statured task force of society could be assembled to convey its support for deceased donation to influence society and resolve these misperceptions.
The World Health Organization is now calling for each member state to achieve a self-sufficiency in organ donation and transplantation "equitably meeting the transplantation needs of a given population using resources from within that population". Patients should not be compelled to go to foreign countries for their organs. Israel has been a leader in the development of a model program intended to address transplant tourism. Insurance companies are no longer permitted to provide resources for Israelis to undergo illegal transplants in foreign destinations. The social necessity of a scientifically and medically applied system of deceased organ donation is now evident so that a sufficient number of organs can be available for patients from within the country they reside.
This manuscript is a survey of the halachic attitudes toward organ transplant procedures from a living donor which can be defined as life-saving procedures for the recipient or at least life-prolonging proce-dures. Three fundamental problems concerning the halachic aspects of such transplantation are dis-cussed in detail: the danger to the donor, donation under coercion, and the sale of organs and tissues. The terms “halacha” and “Jewish law” are defined in the introduction.
