Aging constitutes the central risk factor for major diseases including many forms of cancer, neurodegeneration, and cardiovascular diseases. The aging process is characterized by both global and tissue-specific changes in gene expression across taxonomically diverse species. While aging has historically been thought to entail cell-autonomous, even stochastic changes, recent evidence suggests that modulation of this process can be hierarchal, wherein manipulations of nutrient-sensing neurons (e.g., in the hypothalamus) produce peripheral effects that may modulate the aging process itself. The most robust intervention extending lifespan, plausibly impinging on the aging process, involves different modalities of dietary restriction (DR). Lifespan extension by DR is associated with broad protection against diseases (natural and engineered). Here we review potential epigenetic processes that may link lifespan to age-related diseases, particularly in the context of DR and (other) ketogenic diets, focusing on brain and hypothalamic mechanisms.

Chronic caloric restriction (CR) without malnutrition is known to affect different cellular processes such as stem cell function, cell senescence, inflammation, and metabolism. Despite the differences in the implementation of CR, the reduction of calories produces a widespread beneficial effect in noncommunicable chronic diseases, which can be explained by improvements in immuno-metabolic adaptation. Cellular adaptation that occurs in response to dietary patterns can be explained by alterations in epigenetic mechanisms such as DNA methylation, histone modifications, and microRNA. In this review, we define these modifications and systematically summarize the current evidence related to CR and the epigenome. We then explain the significance of genome-wide epigenetic modifications in the context of disease development. Although substantial evidence exists for the widespread effect of CR on longevity, there is no consensus regarding the epigenetic regulations of the underlying cellular mechanisms that lead to improved health. We provide compelling evidence that CR produces long-lasting epigenetic effects that mediate expression of genes related to immuno-metabolic processes. Epigenetic reprogramming of the underlying chronic low-grade inflammation by CR can lead to immuno-metabolic adaptations that enhance quality of life, extend lifespan, and delay chronic disease onset.

Anxiety disorders are some of the most common psychiatric disorders, with potentially debilitating consequences on individual function. Existing pharmacotherapies for anxiety disorders are limited by delay to therapeutic effect, dependence, tolerance, withdrawal, and abuse potential. Therefore, safe and evidence-based complementary or alternative therapies may be important allies in the care of patients with anxiety disorders. Essential oils are lipophilic and concentrated botanical extracts that exhibit many properties of drugs, although they are not Food and Drug Administration approved and have limitations characteristic of herbal preparations. Lavender essential oil has an extensive anecdotal history of anxiolytic benefit that has recently been supported by clinical efficacy studies. The 2 primary terpenoid constituents of lavender essential oil, linalool and linalyl acetate, may produce an anxiolytic effect in combination via inhibition of voltage-gated calcium channels, reduction of 5HT1receptor activity, and increased parasympathetic tone. The objectives of this article are to provide a brief overview of lavender oil in aromatherapy, explore variability in the constituents of lavender oil, summarize its pharmacology and safety profile, as well as describe its body of research that has been conducted for anxiety.

It is well established that the telomeres at the ends of chromosomes are composed of long arrays of (TTAGGG)n x (CCCTAA)n that form a nucleoprotein complex required for the replication and protection of chromosome ends. Throughout the cell cycle, telomeres also contain a protein component related to the proto-oncogene Myb that is known as TRF1 (telomere TTAGGG repeat binding factor 1) that binds to the duplex array of TTAGGG repeats in the telomere. Previous studies have shown that TRF1 appears to play a role in controlling the length of telomeres by acting as an inhibitor of telomerase. The amount of each of the TRF1(C-19)&TRF1(N-19) was identical to the amount of telomere of the same organ of the same apparently normal individual. Using synthesized basic unit of TTAGGG, as well as CCCTAA, as separate reference control substances for the Bi-Digital O-Ring Test of Resonance Phenomenon between 2 identical substances, we were able to non-invasively measure the approximate amount of TTAGGG and CCCTAA units, in both normal and cancerous human cells. We examined about 30 apparently normal subjects (both Asian and Caucasian in both sex). The subjects' ages ranged from infancy to 76 years. Each subject was first examined using TTAGGG as a control substance and then examined using CCCTAA as a control substance. The amount of telomere in various cancer tissues are almost always higher than that of normal tissue of the same organ. The measured amounts of both TTAGGG and CCCTAA were found to be in an average of 1500-1600 ng for human fetus or infancy and decreased with the advance of age in both sex with the exception of the heart, brain, eyes (retina), testes, and ovaries, which usually remain at the level of the infant, or reduced very little. Individuals in the same age group had a similar range of amounts of both TTAGGG and CCCTAA in the same organ of the same individual, (except for those with unusually low telomeres often had chronic degenerative diseases, and those who had exceptionally high telomere levels often had excellent physical conditions or mental acumen). The amounts of measured TTAGGG and CCCTAA molecules before and after acupuncture on St. 36 in adenocarcinomas and small cell carcinoma coexisting in the lung of a 54-yr.-old Asian male were: telomere in adenocarcinoma decreased from 950 ng to 750 ng and telomere in small cell carcinoma decreased from 770 ng to 600 ng. When the cancer treatment is effective, the amount of telomere is reduced towards the value of the normal internal organ. We found that acupuncture on St.36 on apparently normal subjects increased the telomere levels up to a maximum of more than 2 times their telomere levels prior to the treatment, depending on the method of treatment, but frequently increases were between 60% to 100%. Strong Shiatsu performed on St. 36 produced a somewhat lesser effect than acupuncture. We also determined the amounts of TTAGGG and CCCTAA molecules non-invasively in 3 mummified Egyptian sisters from the 8th Century BC on exhibit at the Museo Egizio in Turin, Italy in order to estimate their approximate ages (at the time of death). The amounts of body telomere were 500 ng, 550 ng, and 750 ng. For the prehistoric Iceman (about 3350 B.C. to 3310 B.C) discovered in 1991 in the Italian Otzal Alps at about 3,200 meters altitude, estimated body telomere was about 400 ng and telomere in brain and heart was 1600 ng, similar to that of a contemporary human being. Although these studies are preliminary, the findings may have potential applications not only in anti-aging, cancer treatments, and pathophysiology of brain and heart, but also for the estimation of the difference in the ages of cadavers studied in archeology and forensic medicine.

Adherence to a healthy diet such as Mediterranean Diet (MD) may exert beneficial effects in university students, promoting their academic performance and quality of life, as well as their mental and physical health status. In this aspect, the present study aimed to critically analyze the current epidemiological evidence concerning MD adherence of university students' populations. PubMed database was comprehensively searched, using relative keywords. Students' dietary habits are moving away from MD guidelines towards unhealthy eating patterns, especially for those living away from home and even for students with a Mediterranean country origin. Most of the available studies have documented that poorer students' health status was associated with lower MD adherence. Higher MD adherence was correlated with lower depression risk, while higher perceived stress score with lower fruit and vegetables intake. The access of students to information and knowledge provided by courses and lectures did not effectively enhance their compliance to MD. Alarmingly enough, the majority of students, even from medical and nutritional university departments, showed inadequate knowledge on healthy eating habits. Due to the influence of diet on the quality of life and the mental and physical health of students, it is crucial to redirect research focus on this important aspect.

Accumulating evidences suggest that foods that were regularly consumed during the human primates and evolution, in particular during the Paleolithic era (2.6-0.01 x 10(6) years ago), may be optimal for the prevention and treatment of some chronic diseases. It has been postulated that fundamental changes in the diet and other lifestyle conditions that occurred after the Neolithic Revolution, and more recently with the beginning of the Industrial Revolution are too recent taking into account the evolutionary time scale for the human genome to have completely adjust. In contemporary Western populations at least 70% of daily energy intake is provided by foods that were rarely or never consumed by Paleolithic hunter-gatherers, including grains, dairy products as well as refined sugars and highly processed fats. Additionally, compared with Western diets, Paleolithic diets, based on recently published estimates of macronutrient and fatty acid intakes from an East African Paleolithic diet, contained more proteins and long-chain polyunsaturated fatty acids, and less linoleic acid. Observational studies of hunter-gatherers and other non-western populations lend support to the notion that a Paleolithic type diet may reduce the risk of cardiovascular disease, metabolic syndrome, type 2 diabetes, cancer, acne vulgaris and myopia. Moreover, preliminary intervention studies using contemporary diet based on Paleolithic food groups (meat, fish, shellfish, fresh fruits and vegetables, roots, tubers, eggs, and nuts), revealed promising results including favorable changes in risk factors, such as weight, waist circumference, C-reactive protein, glycated haemoglobin (HbAlc), blood pressure, glucose tolerance, insulin secretion, insulin sensitivity and lipid profiles. Low calcium intake, which is often considered as a potential disadvantage of the Paleolithic diet model, should be weighed against the low content of phytates and the low content of sodium chloride, as well as the high amount of net base yielding vegetables and fruits. Increasing number of evidences supports the view that intake of high glycemic foods and insulinotropic dairy products is involved in the pathogenesis and progression of acne vulgaris in Western countries. In this context, diets that mimic the nutritional characteristics of diets found in hunter-gatherers and other non-western populations may have therapeutic value in treating acne vulgaris. Additionally, more studies is needed to determine the impact of gliadin, specific lectins and saponins on intestinal permeability and the pathogenesis of autoimmune diseases.

Hypertension, or the chronic elevation in resting arterial blood pressure (BP), is a significant risk factor for cardiovascular disease and estimated to affect ~1 billion adults worldwide. The goals of treatment are to lower BP through lifestyle modifications (smoking cessation, weight loss, exercise training, healthy eating and reduced sodium intake), and if not solely effective, the addition of antihypertensive medications. In particular, increased physical exercise and decreased sedentarism are important strategies in the prevention and management of hypertension. Current guidelines recommend both aerobic and dynamic resistance exercise training modalities to reduce BP. Mounting prospective evidence suggests that isometric exercise training in normotensive and hypertensive (medicated and non-medicated) cohorts of young and old participants may produce similar, if not greater, reductions in BP, with meta-analyses reporting mean reductions of between 10 and 13 mmHg systolic, and 6 and 8 mmHg diastolic. Isometric exercise training protocols typically consist of four sets of 2-min handgrip or leg contractions sustained at 20-50 % of maximal voluntary contraction, with each set separated by a rest period of 1-4 min. Training is usually completed three to five times per week for 4-10 weeks. Although the mechanisms responsible for these adaptations remain to be fully clarified, improvements in conduit and resistance vessel endothelium-dependent dilation, oxidative stress, and autonomic regulation of heart rate and BP have been reported. The clinical significance of isometric exercise training, as a time-efficient and effective training modality to reduce BP, warrants further study. This evidence-based review aims to summarize the current state of knowledge regarding the effects of isometric exercise training on resting BP.

Recent systematic reviews (SRs) came to divergent conclusions on the efficacy and safety of medical marijuana and cannabis-based medicines for chronic pain management. This paper gives an overview and critical appraisal of the methods of recent SRs of randomized controlled trials (RCTs) with cannabis medicines for chronic pain.Selective search of the literature, incorrect data analyses and presentation in favor of cannabis medicines can be detected in both RCTs and SRs. The more detailed the search of literature (e.g. inclusion of so-called grey literature) and the higher the criteria of the inclusion of studies (such as study duration) and of the clinical relevance of the study findings, the more disappointing are the conclusions of SRs on the efficacy and safety of cannabis medicines. There is moderate quality evidence of a moderate relief of neuropathic pain. Cannabis medicines can be regarded to be third-line therapy for chronic neuropathic pain. There are signals of a lack of efficacy for all other chronic pain syndromes.New high-quality RCTs and approaches, such as network meta-analyses combining different treatments and controlled and observational including additional outcomes than pain relief, are necessary to better define the importance of cannabis medicines for chronic pain management.

The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin Dfor a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40-60 ng/mL (100-150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin Ddoses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

BACKGROUND AND AIM:Functional gastrointestinal symptoms are common and their management is often a difficult clinical problem. The link between food intake and symptom induction is recognized. This review aims to describe the evidence base for restricting rapidly fermentable, short-chain carbohydrates (FODMAPs) in controlling such symptoms.

METHODS:The nature of FODMAPs, their mode of action in symptom induction, results of clinical trials and the implementation of the diet are described.

RESULTS:FODMAPs are widespread in the diet and comprise a monosaccharide (fructose), a disaccharide (lactose), oligosaccharides (fructans and galactans), and polyols. Their ingestion increases delivery of readily fermentable substrate and water to the distal small intestine and proximal colon, which are likely to induce luminal distension and induction of functional gut symptoms. The restriction of their intake globally (as opposed to individually) reduces functional gut symptoms, an effect that is durable and can be reversed by their reintroduction into the diet (as shown by a randomized placebo-controlled trial). The diet has a high compliance rate. However it requires expert delivery by a dietitian trained in the diet. Breath hydrogen tests are useful to identify individuals who can completely absorb a load of fructose and lactose so that dietary restriction can be less stringent.

CONCLUSIONS:The low FODMAP diet provides an effective approach to the management of patients with functional gut symptoms. The evidence base is now sufficiently strong to recommend its widespread application.

Anxiety disorders are a group of highly prevalent mental health conditions that can have a debilitating impact on daily functioning and well-being. They can co-occur with other mental health disorders, such as depression. People with anxiety disorders are also at an elevated risk of cardiovascular disease and premature mortality. Physical activity appears to be protective against anxiety disorders in clinical and nonclinical populations. Exercise, a subset of physical activity, has been shown to significantly reduce the symptoms of anxiety. The mechanisms through which exercise produces these effects are likely to involve a combination of biological and psychological factors. Physical activity may also be useful in reducing the symptoms of comorbid mental health conditions and the risk of physical health complications over time. Promoting physical activity could be a method of preventing or treating anxiety disorders with a wide range of benefits. However, further research will be necessary to address important gaps in the literature before these approaches can be fully implemented in mental health services.

There is robust evidence that habitual physical activity is anti-inflammatory and protective against developing chronic inflammatory disease. Much less is known about the effects of habitual moderate exercise in the gut, the compartment that has the greatest immunological responsibility and interactions with the intestinal microbiota. The link between the two has become evident, as recent studies have linked intestinal dysbiosis, or the disproportionate balance of beneficial to pathogenic microbes, with increased inflammatory disease susceptibility. Limited animal and human research findings imply that exercise may have a beneficial role in preventing and ameliorating such diseases by having an effect on gut immune function and, recently, microbiome characteristics. Emerging data from our laboratory show that different forms of exercise training differentially impact the severity of intestinal inflammation during an inflammatory insult (for example, ulcerative colitis) and may be jointly related to gut immune cell homeostasis and microbiota-immune interactions. The evidence we review and present will provide data in support of rigorous investigations concerning the effects of habitual exercise on gut health and disease.

PURPOSE OF REVIEW:This review intends to characterize the recent literature pertaining to the role of aerobic exercise in the prevention of migraine. Areas of consensus within that literature may be used to guide clinical practice, allowing for the promulgation of evidence-based practice recommendations.

RECENT FINDINGS:The past decade has seen the publication of numerous high-quality studies that explore aspects of exercise's effects on migraine prevention, including its success as a stand-alone prevention strategy, as well as its non-inferiority to some pharmacologic preventive measures. Exercise often tops providers' lists of recommended lifestyle modifications that help reduce migraine burden. Biologically, exercise suppresses inflammatory modulators, including numerous cytokines, and stress hormones, like growth hormone and cortisol. Exercise has also been shown to affect microvascular health, which may be implicated in cortical spreading depression. Psychologically, there is evidence that exercise improves migraine self-efficacy and internalizes the locus of control, leading to reduced migraine burden. Randomized control trials have demonstrated that a sufficiently rigorous aerobic exercise regimen alone is sufficient to yield a statistically significant reduction in migraine frequency, intensity, and duration. Higher-intensity training appears to confer more benefit. Studies have also demonstrated non-inferiority of exercise compared with certain pharmacologic prophylactic interventions, like topiramate. However, the addition of exercise to a traditional preventive regimen may provide added benefit. Special populations, like those with comorbid neck pain or tension headache, may benefit from exercise; and patients who cannot tolerate high-impact exercise may even benefit from low-impact exercise like yoga. Therefore, exercise is a reasonable evidence-based recommendation for migraine prevention.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) with an estimated prevalence approaching 1 million adults in the United States. The disease pathogenesis and resulting damage express as dysfunction (e.g., walking and cognitive impairment) and symptoms (e.g., fatigue and depression) that compromise quality of life (QOL) and full participation. There has been a steadily increasing body of research on the outcomes of exercise among persons with MS, and this has accelerated sharply over the past decade. The current chapter provides a review of exercise and its outcomes, safety, and prescription in MS. This chapter initially reviews the evidence for benefits of exercise based principally on meta-analyses and literature reviews. The chapter then reviews evidence on the safety of exercise in MS and lastly provides guidelines for exercise prescription in MS. Collectively, this chapter serves as an overview and reference for researchers and clinicians interested in the benefits, safety, and prescription of exercise in MS.

Chronic noncommunicable diseases (CNCDs), which include cardiovascular disease, some cancers, for example, colon cancer, breast cancer, and type 2 diabetes, are reaching epidemic proportions worldwide. It has now become clear that low-grade chronic inflammation is a key player in the pathogenesis of most CNCDs. Given that regular exercise offers protection against all causes of mortality, primarily by protection against atherosclerosis and insulin resistance, we suggest that exercise may exert some of its beneficial health effects by inducing anti-inflammatory actions. Recently, IL-6 was introduced as the first myokine, defined as a cytokine, which is produced and released by contracting skeletal muscle fibres, exerting its effects in other organs of the body. We suggest that skeletal muscle is an endocrine organ and that myokines may be involved in mediating the beneficial effects against CNCDs associated with low-grade inflammation.

Exercise may be described as a polypill to prevent and/or treat almost every chronic disease, with obvious benefits such as its low cost and practical lack of adverse effects. Implementing physical activity interventions in public health is therefore a goal at the medical, social, and economic levels. This chapter describes the importance of health promotion through physical activity and discusses the impacts of exercise on the most prevalent chronic diseases, namely metabolic syndrome-related disorders, cardiovascular diseases, cancer, and Alzheimer's disease. For each of these chronic conditions, we discuss the epidemiological evidence supporting a beneficial role of exercise, provide guidelines for exercise prescription, and describe the biological mechanisms whereby exercise exerts its modulatory effects.

Diabetes mellitus is associated with cardiovascular, ophthalmic, and renal comorbidities. Among these, diabetic cardiomyopathy (DCM) causes the most severe symptoms and is considered to be a major health problem worldwide. Exercise is widely known as an effective strategy for the prevention and treatment of many chronic diseases. Importantly, the onset of complications arising due to diabetes can be delayed or even prevented by exercise. Regular exercise is reported to have positive effects on diabetes mellitus and the development of DCM. The protective effects of exercise include prevention of cardiac apoptosis, fibrosis, oxidative stress, and microvascular diseases, as well as improvement in cardiac mitochondrial function and calcium regulation. This review summarizes the recent scientific findings to describe the potential mechanisms by which exercise may prevent DCM and heart failure.

It is now well established, at least in animal models, that exercise elicits potent pro-cognitive and pro-neurogenic effects. Alzheimer's disease (AD) is one of the leading causes of dementia and represents one of the greatest burdens on healthcare systems worldwide, with no effective treatment for the disease to date. Exercise presents a promising non-pharmacological option to potentially delay the onset of or slow down the progression of AD. Exercise interventions in mouse models of AD have been explored and have been found to reduce amyloid pathology and improve cognitive function. More recent studies have expanded the research question by investigating potential pro-neurogenic and anti-inflammatory effects of exercise. In this review we summarise studies that have examined exercise-mediated effects on AD pathology, cognitive function, hippocampal neurogenesis and neuroinflammation in transgenic mouse models of AD. Furthermore, we attempt to identify the optimum exercise conditions required to elicit the greatest benefits, taking into account age and pathology of the model, as well as type and duration of exercise.

Cancer cachexia is a complicated disorder of extreme, progressive skeletal muscle wasting. It is directed by metabolic alterations and systemic inflammation dysregulation. Numerous studies have demonstrated that increased systemic inflammation promotes this type of cachexia and have suggested that cytokines are implicated in the skeletal muscle loss. Exercise is firmly established as an anti-inflammatory therapy that can attenuate or even reverse the process of muscle wasting in cancer cachexia. The interleukin IL-6 is generally considered to be a key player in the development of the microenvironment of malignancy; it promotes tumor growth and metastasis by acting as a bridge between chronic inflammation and cancerous tissue and it also induces skeletal muscle atrophy and protein breakdown. Paradoxically, a beneficial role for IL-6 has also been identified recently, and that is its status as a"founding member"of the myokine class of proteins. Skeletal muscle is an important source of circulating IL-6 in people who participate in exercise training. IL-6 acts as an anti-inflammatory myokine by inhibiting TNFα and improving glucose uptake through the stimulation of AMPK signaling. This review discusses the action of IL-6 in skeletal muscle tissue dysfunction and the role of IL-6 as an"exercise factor"that modulates the immune system. This review also sheds light on the main considerations related to the treatment of muscle wasting in cancer cachexia.

Physical inactivity and psychosocial stress are prevalent in residents of the United States. The purpose of this article is to review the interaction between these 2 conditions and examine the effects of exercise on stress and cardiovascular (CV) health. A query of scientific references between 1974 to 2018 was performed using the PubMed search engine accessing the MEDLINE database using the search terms psychosocial stress, CV disease (CVD), physical activity, exercise, cardiac rehabilitation, and team sports. Psychosocial stress is a strong independent risk factor for adverse CV events. Conversely, people who experience CV events subsequently have drastically elevated rates of new-onset mental health disorders, including depression and anxiety. Psychosocial stress and CVD often trigger self-reinforcing feedback loops that can worsen mental health and cardiac prognosis. Exercise predictably improves CV health and prognosis and also is effective at lowering levels of psychosocial stress. Group exercise in particular seems to provide social support while at the same time boosting fitness levels and, thus, may be the single most important intervention for patients with concomitant CVD and emotional stress. Collaborative physical activity, such as group exercise, team sports, interactive physical play, and cardiac rehabilitation programs, have the potential to improve mental health and CV prognosis.