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.

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 CDKN2A Gene Expression as a Potential Aging Biomarker in Dogs

2021 ◽  
Vol 8 ◽  
Author(s):  
Sára Sándor ◽  
Kitti Tátrai ◽  
Kálmán Czeibert ◽  
Balázs Egyed ◽  
Enikő Kubinyi
Keyword(s):  
Gene Expression ◽  
Kinase Inhibitor ◽  
Brain Aging ◽  
Model Organisms ◽  
Aging Research ◽  
Temporal Muscle ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Age Related ◽  
The Brain

Describing evolutionary conserved physiological or molecular patterns, which can reliably mark the age of both model organisms and humans or predict the onset of age-related pathologies has become a priority in aging research. The age-related gene-expression changes of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene have been well-documented in humans and rodents. However, data is lacking from other relevant species, including dogs. Therefore, we quantified the CDKN2A mRNA abundance in dogs of different ages, in four tissue types: the frontal cortex of the brain, temporal muscle, skin, and blood. We found a significant, positive correlation between CDKN2A relative expression values and age in the brain, muscle, and blood; however, no correlation was detected in the skin. The strongest correlation was detected in the brain tissue (CDKN2A/GAPDH: r = 0.757, p < 0.001), similarly to human findings, while the muscle and blood showed weaker, but significant correlation. Our results suggest that CDKN2A might be a potential blood-borne biomarker of aging in dogs, although the validation and optimization will require further, more focused research. Our current results also clearly demonstrate that the role of CDKN2A in aging is conserved in dogs, regarding both tissue specificity and a pivotal role of CDKN2A in brain aging.

scholarly journals Klotho: An Elephant in Aging Research

2019 ◽  
Vol 74 (7) ◽  
pp. 1031-1042 ◽  
Author(s):  
Amin Cheikhi ◽  
Aaron Barchowsky ◽  
Amrita Sahu ◽  
Sunita N Shinde ◽  
Abish Pius ◽  
...  
Keyword(s):  
Life Span ◽  
Accelerated Aging ◽  
Model Organisms ◽  
Aging Research ◽  
Promising Tool ◽  
Age Related ◽  
Organ Systems ◽  
Single Protein ◽  
20Th Anniversary ◽  
Biology Of Aging

Abstract The year 2017 marked the 20th anniversary of the first publication describing Klotho. This single protein was and is remarkable in that its absence in mice conferred an accelerated aging, or progeroid, phenotype with a dramatically shortened life span. On the other hand, genetic overexpression extended both health span and life span by an impressive 30%. Not only has Klotho deficiency been linked to a number of debilitating age-related illnesses but many subsequent reports have lent credence to the idea that Klotho can compress the period of morbidity and extend the life span of both model organisms and humans. This suggests that Klotho functions as an integrator of organ systems, making it both a promising tool for advancing our understanding of the biology of aging and an intriguing target for interventional studies. In this review, we highlight advances in our understanding of Klotho as well as key challenges that have somewhat limited our view, and thus translational potential, of this potent protein.

scholarly journals Phenotypic Screening in C. elegans as a Tool for the Discovery of New Geroprotective Drugs

2020 ◽  
Vol 13 (8) ◽  
pp. 164 ◽  
Author(s):  
Sven Bulterijs ◽  
Bart P. Braeckman
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Aging Process ◽  
Population Aging ◽  
Model Organisms ◽  
Pharmacological Interventions ◽  
C Elegans ◽  
System A ◽  
Age Related ◽  
Screening Strategies

Population aging is one of the largest challenges of the 21st century. As more people live to advanced ages, the prevalence of age-related diseases and disabilities will increase placing an ever larger burden on our healthcare system. A potential solution to this conundrum is to develop treatments that prevent, delay or reduce the severity of age-related diseases by decreasing the rate of the aging process. This ambition has been accomplished in model organisms through dietary, genetic and pharmacological interventions. The pharmacological approaches hold the greatest opportunity for successful translation to the clinic. The discovery of such pharmacological interventions in aging requires high-throughput screening strategies. However, the majority of screens performed for geroprotective drugs in C. elegans so far are rather low throughput. Therefore, the development of high-throughput screening strategies is of utmost importance.

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 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.

scholarly journals Lysosomes, Autophagy, and Hormesis in Cell Physiology, Pathology, and Age-Related Disease

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093422 ◽  
Author(s):  
Michael N. Moore
Keyword(s):  
Intracellular Signaling ◽  
Adenosine Monophosphate ◽  
Target Of Rapamycin ◽  
Cell Physiology ◽  
Mechanistic Target Of Rapamycin ◽  
Age Related ◽  
Mechanistic Basis ◽  
The Many ◽  
Mtor Complex 1

Autophagy has been strongly linked with hormesis, however, it is only relatively recently that the mechanistic basis underlying this association has begun to emerge. Lysosomal autophagy is a group of processes that degrade proteins, protein aggregates, membranes, organelles, segregated regions of cytoplasm, and even parts of the nucleus in eukaryotic cells. These degradative processes are evolutionarily very ancient and provide a survival capability for cells that are stressed or injured. Autophagy and autophagic dysfunction have been linked with many aspects of cell physiology and pathology in disease processes; and there is now intense interest in identifying various therapeutic strategies involving its regulation. The main regulatory pathway for augmented autophagy is the mechanistic target of rapamycin (mTOR) cell signaling, although other pathways can be involved, such as 5′-adenosine monophosphate-activated protein kinase. Mechanistic target of rapamycin is a key player in the many highly interconnected intracellular signaling pathways and is responsible for the control of cell growth among other processes. Inhibition of mTOR (specifically dephosphorylation of mTOR complex 1) triggers augmented autophagy and the search is on the find inhibitors that can induce hormetic responses that may be suitable for treating many diseases, including many cancers, type 2 diabetes, and age-related neurodegenerative conditions.

scholarly journals A Narrative Review on Sarcopenia in Type 2 Diabetes Mellitus: Prevalence and Associated Factors

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 183
Author(s):  
Anna Izzo ◽  
Elena Massimino ◽  
Gabriele Riccardi ◽  
Giuseppe Della Pepa
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Elderly Population ◽  
The Elderly ◽  
Narrative Review ◽  
Macrovascular Complications ◽  
Diabetic Patients ◽  
Age Related

Type 2 diabetes mellitus (T2DM) represents a major health burden for the elderly population, affecting approximately 25% of people over the age of 65 years. This percentage is expected to increase dramatically in the next decades in relation to the increased longevity of the population observed in recent years. Beyond microvascular and macrovascular complications, sarcopenia has been described as a new diabetes complication in the elderly population. Increasing attention has been paid by researchers and clinicians to this age-related condition—characterized by loss of skeletal muscle mass together with the loss of muscle power and function—in individuals with T2DM; this is due to the heavy impact that sarcopenia may have on physical and psychosocial health of diabetic patients, thus affecting their quality of life. The aim of this narrative review is to provide an update on: (1) the risk of sarcopenia in individuals with T2DM, and (2) its association with relevant features of patients with T2DM such as age, gender, body mass index, disease duration, glycemic control, presence of microvascular or macrovascular complications, nutritional status, and glucose-lowering drugs. From a clinical point of view, it is necessary to improve the ability of physicians and dietitians to recognize early sarcopenia and its risk factors in patients with T2DM in order to make appropriate therapeutic approaches able to prevent and treat this condition.

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