Autophagy is a lysosomal degradation process and protective housekeeping mechanism to eliminate damaged organelles, long-lived misfolded proteins and invading pathogens. Autophagy functions to ...recycle building blocks and energy for cellular renovation and homeostasis, allowing cells to adapt to stress. Modulation of autophagy is a potential therapeutic target for a diverse range of diseases, including metabolic conditions, neurodegenerative diseases, cancers and infectious diseases. Traditionally, food deprivation and calorie restriction (CR) have been considered to slow aging and increase longevity. Since autophagy inhibition attenuates the anti-aging effects of CR, it has been proposed that autophagy plays a substantive role in CR-mediated longevity. Among several stress stimuli inducers of autophagy, fasting and CR are the most potent non-genetic autophagy stimulators, and lack the undesirable side effects associated with alternative interventions. Despite the importance of autophagy, the evidence connecting fasting or CR with autophagy promotion has not previously been reviewed. Therefore, our objective was to weigh the evidence relating the effect of CR or fasting on autophagy promotion. We conclude that both fasting and CR have a role in the upregulation of autophagy, the evidence overwhelmingly suggesting that autophagy is induced in a wide variety of tissues and organs in response to food deprivation.
Diet development today tends to lead to accelerated growth of chronic diseases. Obesity plays a negative role in the development of chronic disease. This risk factor also occurs in the aging process. ...The condition of organ tissue dysfunction and cell death that occurs with aging also occurs in obesity due to chronic inflammation. This study analyzes the beneficial effects of applying Calorie Restriction (CR) or Energy Restriction (PE) to achieve a long life span, especially in obese individuals. This article is a literature review study with qualitative analysis by searching the PubMed electronic database from February to July 2021 and searching for articles through Meta-analysis, Review, and Systematic Review. Six articles have high relevance. References obtained were compiled and reviewed by summarizing and analyzed by triangulation. Furthermore, examining previous research's pros and cons finally gives alternative solutions. The results of the study showed the application of the PE method by reducing daily energy consumption without causing the risk of malnutrition because it still considers an essential nutrient. In conclusion, the benefits of PE have an impact on slowing down aging molecularly. Slowing down the aging process can increase a person's life expectancy.
•sRAGE and its isoforms cleaved − cRAGE and secretory-esRAGE are low in obese patients and are not modified by moderate caloric restriction.•Proinflammatory EN-RAGE, an endogenous receptor ligand for ...AGE, elevated in obese subjects, is modified by moderate caloric restriction.•EN-RAGE instead of RAGE isoforms could help indicate a better outcome of moderate.
AGEs, their receptor (RAGE), and the extracellular newly identified receptor for AGEs product-binding protein (EN-RAGE) are implicated in the pathogenesis of inflammation.
We analyzed serum EN-RAGE, soluble RAGE (sRAGE), and their isoforms: endogenous secretory − esRAGE and cleaved − cRAGE concentrations in lean controls (n = 74) and in patients with obesity (n = 71) treated for three weeks with moderate calorie restriction (CR) combined with physical activity in a hospital condition.
Using the ELISA method, serum sRAGE, esRAGE, and EN-RAGE were measured before and after CR.
The serum level of sRAGE and esRAGE in patients with obesity was lower than that in non-obese individuals, contrary to cRAGE. EN-RAGE concentration was about three times higher in obese patients. Gradually, a rise in BMI resulted in sRAGE, esRAGE reduction, and EN-RAGE increase. The sRAGE concentration was sex-dependent, indicating a higher value in lean men. A moderate negative correlation was observed between BMI and all RAGE isoforms, whereas EN-RAGE displays a positive correlation. CR resulted in an expected decrease in anthropometric, metabolic, and proinflammatory parameters and EN-RAGE, but no RAGE isoforms. The ratio EN-RAGE/sRAGE was higher in obese humans than in control and was not modified by CR.
Obesity decreases sRAGE and esRAGE and increases EN-RAGE concentration. Moderate CR and physical activity by decreasing inflammation reduces EN-RAGE but is insufficient to increase sRAGE and esRAGE to the extent observed in lean patients.
EN-RAGE instead of sRAGE could be helpful to indicate a better outcome of moderate dietary intervention in obese subjects.
Sirtuin is an essential factor that delays cellular senescence and extends the organismal lifespan through the regulation of diverse cellular processes. Suppression of cellular senescence by Sirtuin ...is mainly mediated through delaying the age-related telomere attrition, sustaining genome integrity and promotion of DNA damage repair. In addition, Sirtuin modulates the organismal lifespan by interacting with several lifespan regulating signaling pathways including insulin/IGF-1 signaling pathway, AMP-activated protein kinase, and forkhead box O. Although still controversial, it is suggested that the prolongevity effect of Sirtuin is dependent with the level of and with the tissue expression of Sirtuin. Since Sirtuin is also believed to mediate the prolongevity effect of calorie restriction, activators of Sirtuin have attracted the attention of researchers to develop therapeutics for age-related diseases. Resveratrol, a phytochemical rich in the skin of red grapes and wine, has been actively investigated to activate Sirtuin activity with consequent beneficial effects on aging. This article reviews the evidences and controversies regarding the roles of Sirtuin on cellular senescence and lifespan extension, and summarizes the activators of Sirtuin including Sirtuin-activating compounds and compounds that increase the cellular level of nicotinamide dinucleotide.
•In a randomized trial, we previously showed that a 20-week calorie restriction (CR) program, with or without aerobic exercise training (AT), resulted in significant weight and fat loss and improved ...exercise capacity. However, little is known regarding the long-term effects after a short-term intervention of CR with or without AT in older obese patients with HFpEF.•Sixteen participants from either the CR or CR+AT who experienced significant weight loss ≥ 2 kg were re-examined after a long-term follow-up without intervention. Compared to the end of the 20-week intervention, mean body weight increased at long-term follow-up (mean 28 months) due to increased fat mass with no change in lean mass, resulting in worse body composition (decreased lean-to-fat mass). Additionally, there was a significant decrease in exercise capacity.•Decreased lean-fat-mass ratio is consistently reported in patients with HFpEF and is associated with exercise intolerance, worsened cardiovascular health, more hospitalizations, and mortality.
Obesity combined with heart failure with preserved ejection fraction (HFpEF) is the dominant form of HF among older persons. In a randomized trial, we previously showed that a 5-month calorie restriction (CR) program, with or without aerobic exercise training (AT), resulted in significant weight and fat loss and improved exercise capacity. However, little is known regarding the long-term effects of these outcomes after a short-term (5-month) intervention of CR with or without AT in older patients with obesity and HFpEF.
Sixteen participants from either the CR or CR+AT who experienced significant weight loss ≥ 2 kg were reexamined after a long-term follow-up endpoint (28.0 ± 10.8 months) without intervention. The follow-up assessment included body weight and composition via dual-energy X-ray absorptiometry and exhaustive cardiopulmonary treadmill exercise testing.
Compared to the 5-month time-point intervention endpoint, at the long-term follow-up endpoint, mean body weight increased +5.2 ± 4.0 kg (90.7 ± 11.2 kg vs 95.9 ± 11.9; P < 0.001) due to increased fat mass (38.9 ± 9.3 vs 43.8 ± 9.8; P < 0.001) with no change in lean mass (49.6 ± 7.1 vs 49.9±7.6; P = 0.67), resulting in worse body composition (decreased lean-to-fat mass). Change in total mass was strongly and significantly correlated with change in fat mass (r = 0.75; P < 0.001), whereas there appeared to be a weaker correlation with change in lean mass (r = 0.50; P = 0.051). Additionally, from the end of the 5-month time-point intervention endpoint to the long-term follow-up endpoint, there were large, significant decreases in VO2peak (-2.2 ± 2.1 mL/kg/min; P = 0.003) and exercise time (-2.4 ± 2.6 min; P = 0.006). There appeared to be an inverse correlation between the change in VO2peak and the change in fat mass (r = -0.52; P = 0.062).
Although CR and CR+AT in older patients with obesity and HFpEF can improve body composition and exercise capacity significantly, these positive changes diminish considerably during long-term follow-up endpoints, and regained weight is predominantly adipose, resulting in worsened overall body composition compared to baseline. This suggests a need for long-term adherence strategies to prevent weight regain and maintain improvements in body composition and exercise capacity following CR in older patients with obesity and HFpEF.
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Improvements in health care have increased human life expectancy in recent decades, and the elderly population is thus increasing in most developed countries. Unfortunately this still means increased ...years of poor health or disability. Since it is not yet possible to modify our genetic background, the best anti-aging strategy is currently to intervene on environmental factors, aiming to reduce the incidence of risk factors of poor health. Calorie restriction (CR) with adequate nutrition is the only non-genetic, and the most consistent non-pharmacological intervention that extends lifespan in model organisms from yeast to mammals, and protects against the deterioration of biological functions, delaying or reducing the risk of many age-related diseases. The biological mechanisms of CR's beneficial effects include modifications in energy metabolism, oxidative stress, insulin sensitivity, inflammation, autophagy, neuroendocrine function and induction of hormesis/xenohormesis response. The molecular signalling pathways mediating the anti-aging effect of CR include sirtuins, peroxisome proliferator activated receptor G coactivator-1α, AMP-activated protein kinase, insulin/insulin growth factor-1, and target of rapamycin, which form a pretty interacting network. However, most people would not comply with such a rigorous dietary program; research is thus increasingly aimed at determining the feasibility and efficacy of natural and/or pharmacological CR mimetic molecules/ treatments without lowering food intake, particularly in mid- to late-life periods. Likely candidates act on the same signalling pathways as CR, and include resveratrol and other polyphenols, rapamycin, 2-deoxy-D-glucose and other glycolytic inhibitors, insulin pathway and AMP-activated protein kinase activators, autophagy stimulators, alpha-lipoic acid, and other antioxidants.
Calorie restriction (CR) without malnutrition increases the health- and lifespan of diverse taxa. The mechanism(s) behind CR are debated but may be directly linked to body composition changes that ...maintain energy balance. During a deficit, energy is primarily obtained from white adipose tissue (WAT; utilized) whilst other tissues remain unchanged (protected) or grow (invested) relative to body mass. The changes in mass of 6 tissues from 48 male C57BL/6 mice following 3-months graded (10, 20, 30, or 40%) CR or fed ad libitum for 12 or 24hr a day were related to cell size (hypo/hypertrophy) and/or number (hypo/hyperplasia). Tissues studied were: retroperitoneal and subcutaneous WAT, brown adipose tissue (BAT) (utilized); lungs (protected), and stomach and caecum (invested). Methodology was based on number of nuclei/ tissue equalling the number of cells. Extracted DNA was quantified and used to estimate cell numbers (Total DNA/DNA per diploid nucleus) and size (Tissue mass/nuclei number). WAT utilization was caused solely by hypotrophy whereas BAT utilization resulted from reduced cell number and size. WAT cell size positively correlated with circulating hormones related to energy balance and BAT cell number and size positively correlated with body temperature. No changes were found in the lungs, consistent with their protected status, whereas hyperplasia appeared to be the dominant mechanism for invested alimentary-tract tissues. These findings indicate the pattern of change of cell size and number across increasing levels of short-term CR is tissue-specific.
SIRT1 and other sirtuins in metabolism Chang, Hung-Chun; Guarente, Leonard
Trends in endocrinology and metabolism,
03/2014, Volume:
25, Issue:
3
Journal Article
Peer reviewed
Open access
Highlights • Sirtuins respond to energy level changes and execute salutary effects resembling calorie restriction (CR) • Sirtuins mediate CR effects in various cellular compartments and are crucial ...metabolic regulators in multiple tissues. • Small molecules that enhance sirtuin activities, including CR mimetics and NAD+ precursors, are promising strategies to ameliorate age-related diseases.
Anabolic resistance and impaired myocellular quality contribute to age-related sarcopenia, which exacerbates with obesity. Diet-induced muscle mass loss is attenuated by resistance or aerobic plus ...resistance exercise compared to aerobic exercise in obese elderly. We assessed chronic effects of weight loss plus different exercise modalities on muscle protein synthesis response to feeding and myocellular quality. Obese older adults were randomized to a weight-management program plus aerobic, resistance, or combined aerobic and resistance exercise or to control. Participants underwent vastus lateralis biopsies at baseline and 6 months. Muscle protein synthesis rate increased more in resistance and combined than in control. Autophagy mediators’ expression decreased more in combined than in aerobic, which experienced a higher increase in inflammation and mitochondrial regulators’ expression. In obese elderly, combined aerobic and resistance exercise is superior to either mode independently for improving muscle protein synthesis and myocellular quality, thereby maintaining muscle mass during weight-loss therapy.
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•Diet-induced weight loss leads to muscle mass reduction in obese older adults•Diet-induced muscle loss is attenuated by addition of resistance exercise•Muscle protein synthesis following a meal improves with resistance exercise•Myocellular quality improves with aerobic plus resistance exercise
Anabolic resistance and impaired myocellular quality contribute to age-related sarcopenia, which worsens with obesity. However, weight-loss programs can exacerbate sarcopenia. Colleluori et al. show that during weight-loss therapy, aerobic plus resistance exercise is more effective than aerobic or resistance exercise alone in improving muscle protein synthesis and myocellular quality, thereby preserving muscle mass in dieting, obese older adults.
Aging, lifestyle and dementia Wahl, Devin; Solon-Biet, Samantha M.; Cogger, Victoria C. ...
Neurobiology of disease,
October 2019, 2019-10-00, 2019-10-01, Volume:
130
Journal Article
Peer reviewed
Open access
Aging is the greatest risk factor for most diseases including cancer, cardiovascular disorders, and neurodegenerative disease. There is emerging evidence that interventions that improve metabolic ...health with aging may also be effective for brain health. The most robust interventions are non-pharmacological and include limiting calorie or protein intake, increasing aerobic exercise, or environmental enrichment. In humans, dietary patterns including the Mediterranean, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) and Okinawan diets are associated with improved age-related health and may reduce neurodegenerative disease including dementia. Rapamycin, metformin and resveratrol act on nutrient sensing pathways that improve cardiometabolic health and decrease the risk for age-associated disease. There is some evidence that they may reduce the risk for dementia in rodents. There is a growing recognition that improving metabolic function may be an effective way to optimize brain health during aging.
•Aging is the greatest risk factor for most chronic diseases, including dementia.•Suboptimal cardiometabolic health is associated with risk of dementia.•Lifestyle and nutrition patterns influence aging and age-related cardiometabolic health.•Interventions that impact aging may also influence brain aging.
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