scholarly journals Mechanisms of Aging and the Preventive Effects of Resveratrol on Age-Related Diseases

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4649
Author(s):  
In Soo Pyo ◽  
Suyeon Yun ◽  
Ye Eun Yoon ◽  
Jung-Won Choi ◽  
Sung-Joon Lee
Keyword(s):  
Energy Metabolism ◽  
Biological Activities ◽  
Nutrient Sensing ◽  
Sirtuin 1 ◽  
Model Organisms ◽  
Cancer Type ◽  
Negative Effects ◽  
Age Related ◽  
Stress Energy

Aging gradually decreases cellular biological functions and increases the risk of age-related diseases. Cancer, type 2 diabetes mellitus, cardiovascular disease, and neurological disorders are commonly classified as age-related diseases that can affect the lifespan and health of individuals. Aging is a complicated and sophisticated biological process involving damage to biochemical macromolecules including DNA, proteins, and cellular organelles such as mitochondria. Aging causes multiple alterations in biological processes including energy metabolism and nutrient sensing, thus reducing cell proliferation and causing cellular senescence. Among the polyphenolic phytochemicals, resveratrol is believed to reduce the negative effects of the aging process through its multiple biological activities. Resveratrol increases the lifespan of several model organisms by regulating oxidative stress, energy metabolism, nutrient sensing, and epigenetics, primarily by activating sirtuin 1. This review summarizes the most important biological mechanisms of aging, and the ability of resveratrol to prevent age-related diseases.

scholarly journals Finding Ponce de Leon’s Pill: Challenges in Screening for Anti-Aging Molecules

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 406 ◽  
Author(s):  
Surinder Kumar ◽  
David B. Lombard
Keyword(s):  
Model Organisms ◽  
Cancer Type ◽  
Pharmacological Interventions ◽  
Aging Research ◽  
Genetic Manipulations ◽  
Age Related ◽  
Probability Of Death ◽  
Invertebrate Models ◽  
Progressive Accumulation

Aging is characterized by the progressive accumulation of degenerative changes, culminating in impaired function and increased probability of death. It is the major risk factor for many human pathologies – including cancer, type 2 diabetes, and cardiovascular and neurodegenerative diseases – and consequently exerts an enormous social and economic toll. The major goal of aging research is to develop interventions that can delay the onset of multiple age-related diseases and prolong healthy lifespan (healthspan). The observation that enhanced longevity and health can be achieved in model organisms by dietary restriction or simple genetic manipulations has prompted the hunt for chemical compounds that can increase lifespan. Most of the pathways that modulate the rate of aging in mammals have homologs in yeast, flies, and worms, suggesting that initial screening to identify such pharmacological interventions may be possible using invertebrate models. In recent years, several compounds have been identified that can extend lifespan in invertebrates, and even in rodents. Here, we summarize the strategies employed, and the progress made, in identifying compounds capable of extending lifespan in organisms ranging from invertebrates to mice and discuss the formidable challenges in translating this work to human therapies.

Sirtuins and Neuropeptide y downregulation in Flinders Sensitive Line Rat Model of Depression

2021 ◽  
pp. 1-19
Author(s):  
Miranda Stiernborg ◽  
Paschalis Efstathopoulos ◽  
Andreas Lennartsson ◽  
Catharina Lavebratt ◽  
Aleksander A. Mathé
Keyword(s):  
Rat Model ◽  
Histone Deacetylases ◽  
Sirtuin 1 ◽  
Model Organisms ◽  
Age Related ◽  
Age Dependent ◽  
Sensitive Line ◽  
And Control ◽  
Temporal Trajectory ◽  
Flinders Sensitive Line

Abstract Objective: Since the NAD+-dependent histone deacetylases sirtuin-1 (SIRT1) and sirtuin-2 (SIRT2) are critically involved in epigenetics, endocrinology and immunology and affect the longevity in model organisms, we investigated their expression in brains of 3 month old and 14-15 month old rat model of depression Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats. In view of the dysregulated NPY system in depression we also studied NPY in young and old FSL to explore the temporal trajectory of depressive-like-ageing interaction. Methods: Sirt1, Sirt2 and Npy mRNA were determined using qRT-PCR in prefrontal cortex (PFC) from young and old FSL and FRL, and in hippocampi from young FSL and FRL. Results: PFC. Sirt1 expression was decreased in FSL (p=0.001). An interaction between age and genotype was found (p=0.032); young FSL had lower Sirt1 with respect to both age (p=0.026) and genotype (p=0.001). Sirt2 was lower in FSL (p=0.003). Npy mRNA was downregulated in FSL (p=0.001) but did not differ between the young and old rat groups. Hippocampus.Sirt1 was reduced in young FSL compared to young FRL (p=0.005). There was no difference in Sirt2 between FSL and FRL. Npy levels were decreased in hippocampus of young FSL compared to young FRL (p=0.003). Effects of ageing could not be investigated due to loss of samples. Conclusions: i. This is the first demonstration that SIRT1 and SIRT2 are changed in brain of FSL, a rat model of depression ; ii. The changes are age dependent; iii. Sirtuins are potential targets for treatment of age-related neurodegenerative diseases.

scholarly journals The Preconditioning of Berberine Suppresses Hydrogen Peroxide-Induced Premature Senescence via Regulation of Sirtuin 1

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaofei Zhu ◽  
Haodi Yue ◽  
Xiaofang Guo ◽  
Jingyi Yang ◽  
Jingshuo Liu ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cellular Senescence ◽  
Sirtuin 1 ◽  
Premature Senescence ◽  
Low Concentration ◽  
Human Diploid Fibroblasts ◽  
Cycle Arrest ◽  
Age Related ◽  
History Of

With a long history of application in Chinese traditional medicine, berberine (BBR) was reported to exhibit healthspan-extending properties in some age-related diseases, such as type 2 diabetes and atherosclerosis. However, the antiaging mechanism of BBR is not completely clear. By means of hydrogen peroxide- (H2O2-) induced premature cellular senescence model, we found that a low-concentration preconditioning of BBR could resist premature senescence in human diploid fibroblasts (HDFs) measured by senescence-associated β-galactosidase (SA-β-gal), accompanied by a decrease in loss of mitochondrial membrane potential and production of intracellular reactive oxygen species (ROS). Moreover, the low-concentration preconditioning of BBR could make cells less susceptible to subsequent H2O2-induced cell cycle arrest and growth inhibition. Experimental results further showed that the low concentration of BBR could induce a slight increase of ROS and upregulate the expression level of sirtuin 1 (SIRT1), an important longevity regulator. H2O2-induced activation of checkpoint kinase 2 (Chk2) was significantly attenuated after the preconditioning of BBR. The present findings implied that the low-concentration preconditioning of BBR could have a mitohormetic effect against cellular senescence triggered by oxidative stress in some age-related diseases through the regulation of SIRT1.

scholarly journals Amino acid transporters and nutrient-sensing mechanisms: new targets for treating insulin-linked disorders?

2007 ◽  
Vol 35 (5) ◽  
pp. 1215-1217 ◽  
Author(s):  
B. Reynolds ◽  
R. Laynes ◽  
M.H. Ögmundsdóttir ◽  
C.A.R. Boyd ◽  
D.C.I. Goberdhan
Keyword(s):  
Amino Acid ◽  
Normal Development ◽  
Nutrient Sensing ◽  
Amino Acid Transporters ◽  
Cancer Type ◽  
Growth Factor Signalling ◽  
In Vivo Analysis ◽  
Signalling Cascade

The IIS (insulin/IGF (insulin-like growth factor) signalling) cascade has an important role in regulating normal development and physiology, as evidenced by its effects in a host of major human diseases including cancer, Type 2 diabetes and neurodegeneration. Recently, it has become clear that multiple types of local nutrient-sensing mechanisms have an impact on cellular insulin-sensitivity through the downstream kinase TOR (target of rapamycin). In vivo analysis in flies has surprisingly highlighted PATs (proton-assisted amino acid transporters) as having a uniquely potent role in regulating IIS/TOR activity and growth, potentially via a novel signalling mechanism. Other molecules such as the heterodimeric amino acid transporter, CD98, which provides the principal route for cellular uptake of leucine, an amino acid implicated in regulating TOR, also appear to have important effects. As our understanding of how nutrient sensing has an impact on IIS/TOR increases, novel targets to modulate aberrant IIS in disease are likely to emerge, which could complement current strategies designed to block kinases in this pathway.

scholarly journals Differential control of ageing and lifespan by isoforms and splice variants across the mTOR network

2017 ◽  
Vol 61 (3) ◽  
pp. 349-368 ◽  
Author(s):  
Patricia Razquin Navas ◽  
Kathrin Thedieck
Keyword(s):  
Causal Relationship ◽  
Splice Variants ◽  
Protein Biosynthesis ◽  
Mammalian Target Of Rapamycin ◽  
Nutrient Sensing ◽  
Metabolic Phenotype ◽  
Model Organisms ◽  
Current View ◽  
Age Related ◽  
Differential Control

Ageing can be defined as the gradual deterioration of physiological functions, increasing the incidence of age-related disorders and the probability of death. Therefore, the term ageing not only reflects the lifespan of an organism but also refers to progressive functional impairment and disease. The nutrient-sensing kinase mTOR (mammalian target of rapamycin) is a major determinant of ageing. mTOR promotes cell growth and controls central metabolic pathways including protein biosynthesis, autophagy and glucose and lipid homoeostasis. The concept that mTOR has a crucial role in ageing is supported by numerous reports on the lifespan-prolonging effects of the mTOR inhibitor rapamycin in invertebrate and vertebrate model organisms. Dietary restriction increases lifespan and delays ageing phenotypes as well and mTOR has been assigned a major role in this process. This may suggest a causal relationship between the lifespan of an organism and its metabolic phenotype. More than 25 years after mTOR’s discovery, a wealth of metabolic and ageing-related effects have been reported. In this review, we cover the current view on the contribution of the different elements of the mTOR signalling network to lifespan and age-related metabolic impairment. We specifically focus on distinct roles of isoforms and splice variants across the mTOR network. The comprehensive analysis of mouse knockout studies targeting these variants does not support a tight correlation between lifespan prolongation and improved metabolic phenotypes and questions the strict causal relationship between them.

scholarly journals Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer’s Disease Treatment

2021 ◽  
Vol 14 (9) ◽  
pp. 890
Author(s):  
Saghar Rabiei Poor ◽  
Miren Ettcheto ◽  
Amanda Cano ◽  
Elena Sanchez-Lopez ◽  
Patricia Regina Manzine ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Adenosine Monophosphate ◽  
Sirtuin 1 ◽  
Health Concern ◽  
Therapeutic Effects ◽  
Age Related

Alzheimer’s disease (AD) is one of the most devastating brain disorders. Currently, there are no effective treatments to stop the disease progression and it is becoming a major public health concern. Several risk factors are involved in the progression of AD, modifying neuronal circuits and brain cognition, and eventually leading to neuronal death. Among them, obesity and type 2 diabetes mellitus (T2DM) have attracted increasing attention, since brain insulin resistance can contribute to neurodegeneration. Consequently, AD has been referred to “type 3 diabetes” and antidiabetic medications such as intranasal insulin, glitazones, metformin or liraglutide are being tested as possible alternatives. Metformin, a first line antihyperglycemic medication, is a 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activator hypothesized to act as a geroprotective agent. However, studies on its association with age-related cognitive decline have shown controversial results with positive and negative findings. In spite of this, metformin shows positive benefits such as anti-inflammatory effects, accelerated neurogenesis, strengthened memory, and prolonged life expectancy. Moreover, it has been recently demonstrated that metformin enhances synaptophysin, sirtuin-1, AMPK, and brain-derived neuronal factor (BDNF) immunoreactivity, which are essential markers of plasticity. The present review discusses the numerous studies which have explored (1) the neuropathological hallmarks of AD, (2) association of type 2 diabetes with AD, and (3) the potential therapeutic effects of metformin on AD and preclinical models.

scholarly journals A novel approach of human geroprotector discovery by targeting the converging subnetworks of aging and age-related diseases

2018 ◽  
Author(s):  
Jialiang Yang ◽  
Bin Zhang ◽  
Sander Houten ◽  
Eric Schadt ◽  
Jun Zhu ◽  
...  
Keyword(s):  
Model Organisms ◽  
Human Longevity ◽  
Effective Interventions ◽  
Age Related ◽  
Novel Approach ◽  
Transcriptional Changes ◽  
Speed Up ◽  
Genetic Interventions ◽  
Novel Strategy

AbstractA key goal of geroscience research is to discover effective interventions to extend human healthspan, the years of healthy life. Currently, majority of the geroprotectors are found by testing compounds in model organisms; whether these compounds will be effective in humans is largely unknown. Here we present a novel strategy called ANDRU (aging network based drug discovery) to help the discovery of human geroprotectors. Instead of relying on model organisms, this approach is driven by human genomic and pharmacogenomic data. It first identifies human aging subnetworks that putatively function at the interface between aging and age-related diseases; it then screens for pharmacological or genetic interventions that may “reverse” the age-associated transcriptional changes seen in these subnetworks. We applied ANDRU to human adipose and artery tissues. In adipose tissue, PTPN1, a target for diabetes treatment and APOE, a known genetic factor for human longevity and diseases like Alzheimer’s disease, were ranked at the top. For small molecules, conjugated linoleic acid and metformin, a drug commonly used to treat type 2 diabetes, were ranked among the top compounds. In artery tissue, N-methyl-D-aspartate antagonists and curcumin were ranked at the top. In summary, ANDRU represents a promising human data-driven strategy that may speed up the discovery of interventions to extend human healthspan.

scholarly journals Peripheral and central regulation of insulin by the intestine and microbiome

2020 ◽  
Author(s):  
Jonathan D. Schertzer ◽  
Tony K.T. Lam
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Nutrient Sensing ◽  
Sirtuin 1 ◽  
High Fat ◽  
Paracrine Factors ◽  
Insulin Homeostasis ◽  
Small Intestinal

Blood glucose and insulin homeostasis is disrupted during the progression of type 2 Diabetes. Insulin levels and action are regulated by both peripheral and central responses that involve the intestine and microbiome. The intestine and its microbiota process nutrients and generate molecules that influence blood glucose and insulin. Peripheral insulin regulation is regulated by gut-segment dependent nutrient sensing and microbial factors such as short chain fatty acids and bile acids that engage G-protein coupled receptors. Innate immune sensing of gut-derived bacterial cell wall components and lipopolysaccharides also alter insulin homeostasis. These bacterial metabolites and postbiotics influence insulin secretion and insulin clearance in part by altering endocrine responses such as glucagon-like peptide-1. Gut-derived bacterial factors can promote inflammation and insulin resistance, but other postbiotics can be insulin sensitizers. In parallel, activation of small intestinal sirtuin 1 increases insulin sensitivity by reversing high-fat induced hypothalamic insulin resistance through a gut-brain neuronal axis, while high-fat feeding alters small intestinal microbiome and increases taurochenodeoxycholic acid in the plasma and the dorsal vagal complex to induce insulin resistance. In summary, emerging evidence indicates that intestinal molecular signaling involving nutrient sensing and the host-microbe symbiosis alter insulin homeostasis and action. Gut-derived host endocrine and paracrine factors as well as microbial metabolites act on the liver, pancreas, the brain and in parallel on the gut-brain neuronal axis. Understanding common nodes of peripheral and central insulin homeostasis and action may reveal new ways to target the intestinal host-microbe relationship in obesity, metabolic disease and type 2 diabetes.

scholarly journals Mammalian models of extended healthy lifespan

2011 ◽  
Vol 366 (1561) ◽  
pp. 99-107 ◽  
Author(s):  
Colin Selman ◽  
Dominic J. Withers
Keyword(s):  
The Elderly ◽  
Ageing Process ◽  
Model Organisms ◽  
Pathological Conditions ◽  
Age Related ◽  
Age Related Cognitive Decline ◽  
Developed World ◽  
Genetic Mutants ◽  
Genetic Mouse Models

Over the last two centuries, there has been a significant increase in average lifespan expectancy in the developed world. One unambiguous clinical implication of getting older is the risk of experiencing age-related diseases including various cancers, dementia, type-2 diabetes, cataracts and osteoporosis. Historically, the ageing process and its consequences were thought to be intractable. However, over the last two decades or so, a wealth of empirical data has been generated which demonstrates that longevity in model organisms can be extended through the manipulation of individual genes. In particular, many pathological conditions associated with the ageing process in model organisms, and importantly conserved from nematodes to humans, are attenuated in long-lived genetic mutants. For example, several long-lived genetic mouse models show attenuation in age-related cognitive decline, adiposity, cancer and glucose intolerance. Therefore, these long-lived mice enjoy a longer period without suffering the various sequelae of ageing. The greatest challenge in the biology of ageing is to now identify the mechanisms underlying increased healthy lifespan in these model organisms. Given that the elderly are making up an increasingly greater proportion of society, this focused approach in model organisms should help identify tractable interventions that can ultimately be translated to humans.

scholarly journals Effect of Exercise on Secondary Sarcopenia: A Comprehensive Literature Review

Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 51
Author(s):  
Rashmi Supriya ◽  
Kumar Purnendu Singh ◽  
Yang Gao ◽  
Yaodong Gu ◽  
Julien S. Baker
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Lung Disease ◽  
Exercise Intervention ◽  
Neurological Diseases ◽  
Cancer Type ◽  
Age Related ◽  
Research Initiatives ◽  
The Impact

Background: Sarcopenia has been recognized as an inevitable part of aging. However, its severity and the age at which it begins cannot be predicted by age alone. The condition can be categorized into primary or age-related sarcopenia and secondary sarcopenia. Sarcopenia is diagnosed as primary when there are no other specific causes. However, secondary sarcopenia occurs if other factors, including malignancy or organ failure, are evident in addition to aging. The prevalence of secondary sarcopenia is far greater than that of primary sarcopenia and requires special attention. To date, nutrition and exercise have proven to be the best methods to combat this disease. The impact of exercise on subjects suffering from sarcopenia with a specific morbidity is worthy of examination for understanding and prevention. The purpose of this review, therefore, is to summarize recent research that has investigated the impact of exercise in patients with secondary sarcopenia, specifically with one comorbidity. Methods: Pubmed, Web of Science, Embase and Medline databases were searched comprehensively with no date limit for randomized controlled trials. The literature was specifically searched for clinical trials in which subjects were sarcopenic with only one comorbidity participating in an exercise intervention. The most visible comorbidities identified and used in the search were lung disease, kidney disease, heart disease, type 2 diabetes, cancer, neurological diseases, osteoporosis and arthritis. Results: A total of 1752 studies were identified that matched the keywords. After removing duplicates, there were 1317 articles remaining. We extracted 98 articles for full screening. Finally, we included 21 relevant papers that were used in this review. Conclusion: Despite a strong rationale for using exercise to improve muscle mass, quality or physical function in subjects with cancer, type 2 diabetes, kidney disease, lung disease and many more, baseline sarcopenia evaluation has been reported in very few trials. The limited number of studies does not allow us to conclude that exercise can improve sarcopenia in patients with other comorbidities. This review highlights the necessity for wide-ranging research initiatives involving secondary sarcopenic patients.

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