scholarly journals The unrecognized potential of pet cats for studying aging and age-related diseases

2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Warren Ladiges ◽  
Keyword(s):  
Older People ◽  
Scientific Community ◽  
Population Stratification ◽  
Healthy Aging ◽  
Genomic Diversity ◽  
Therapeutic Interventions ◽  
Translational Model ◽  
Aging Research ◽  
Age Related ◽  
Keywords Aging

Old cats develop chronic diseases similar to diseases in older people. One-fourth of American households own cats, and almost half are more than 7 years old. Cats share the same environment and are exposed to many of the same chemical stresses. In addition, genomic diversity and population stratification are similar to that occurring in people. With these comparative features, the aging cat represents a geroscience model to investigate the pathogenesis and therapeutic interventions for aging. However, cats are generally not recognized as a translational model for aging research mainly because of the lack of knowledge and appreciation within the scientific community. In addition, cat owners are not aware of any research programs designed to enhance healthy aging in their pets because none exist. Much work is needed to inform and educate the scientific community as well as cat owners about the power of aging cats as a transformative model to investigate aging and age-related diseases that will benefit both human and feline health. Keywords: Aging cats, age-related diseases, healthy aging, geroscience

scholarly journals Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease

Gerontology ◽  
2016 ◽  
Vol 63 (2) ◽  
pp. 103-117 ◽  
Author(s):  
Cia-Hin Lau ◽  
Yousin Suh
Keyword(s):  
Animal Models ◽  
Genetic Manipulation ◽  
Logic Gate ◽  
Therapeutic Interventions ◽  
Human Aging ◽  
Aging Research ◽  
Epigenome Editing ◽  
Related Disease ◽  
Age Related

The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations.

scholarly journals Exploring the Relevance of Senotherapeutics for the Current SARS-CoV-2 Emergency and Similar Future Global Health Threats

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 909 ◽  
Author(s):  
Marco Malavolta ◽  
Robertina Giacconi ◽  
Dario Brunetti ◽  
Mauro Provinciali ◽  
Fabrizio Maggi
Keyword(s):  
Influenza Virus ◽  
Inflammatory Response ◽  
Older People ◽  
Death Rate ◽  
Rna Viruses ◽  
Therapeutic Strategies ◽  
Aging Research ◽  
Age Related ◽  
Biomedical Aging ◽  
Biomedical Aging Research

The higher death rate caused by COVID-19 in older people, especially those with comorbidities, is a challenge for biomedical aging research. Here we explore the idea that an exacerbated inflammatory response, in particular that mediated by IL-6, may drive the deleterious consequences of the infection. Data shows that other RNA viruses, such as influenza virus, can display enhanced replication efficiency in senescent cells, suggesting that the accumulation of senescent cells with aging and age-related diseases may play a role in this phenomenon. However, at present, we are completely unaware of the response to SARS-CoV and SARS-COV-2 occurring in senescent cells. We deem that this is a priority area of research because it could lead to the development of several therapeutic strategies based on senotherapeutics or prevent unsuccessful attempts. Two of these senotherapeutics, azithromycin and ruxolitinib, are currently undergoing testing for their efficacy in treating COVID-19. The potential of these strategies is not only for ameliorating the consequences of the current emergence of SARS-CoV-2, but also for the future emergence of new viruses or mutated ones for which we are completely unprepared and for which no vaccines are available.

scholarly journals Resveratrol: A Sirtuin Activator and The Fountain of Youth

2015 ◽  
Vol 7 (1) ◽  
pp. 1 ◽  
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Caloric Restriction ◽  
Healthy Aging ◽  
Myocardial Infarct ◽  
Functional Decline ◽  
Steady Increase ◽  
Healthy Human ◽  
Aging Research ◽  
Human Lifespan ◽  
Age Related ◽  
Fountain Of Youth

BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life.CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Resveratrol have been shown to prevent and reduce the severity of age-related diseases such as atherosclerosis, stroke, myocardial infarct, diabetes, neurodegenerative diseases, osteoarthritis, tumors and metabolic syndrome, along with their ability to extend lifespan.SUMMARY: The purpose of aging research is the identification of interventions that may avoid or ameliorate the ravages of time. In other words, the quest is for healthy aging, where improved longevity is coupled to a corresponding healthspan extension. It is only by extending the healthy human lifespan that we will truly meet the premise of the Roman poet Cicero: “No one is so old as to think that he may not live a year.”KEYWORDS: aging, caloric restriction, mimetic, healthspan, sirtuin activator

Aging and insulin secretion

2003 ◽  
Vol 284 (1) ◽  
pp. E7-E12 ◽  
Author(s):  
Annette M. Chang ◽  
Jeffrey B. Halter
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Older People ◽  
Glucose Intolerance ◽  
Therapeutic Interventions ◽  
Β Cell ◽  
Insulin Levels ◽  
Cell Dysfunction ◽  
Age Related

Glucose tolerance progressively declines with age, and there is a high prevalence of type 2 diabetes and postchallenge hyperglycemia in the older population. Age-related glucose intolerance in humans is often accompanied by insulin resistance, but circulating insulin levels are similar to those of younger people. Under some conditions of hyperglycemic challenge, insulin levels are lower in older people, suggesting β-cell dysfunction. When insulin sensitivity is controlled for, insulin secretory defects have been consistently demonstrated in aging humans. In addition, β-cell sensitivity to incretin hormones may be decreased with advancing age. Impaired β-cell compensation to age-related insulin resistance may predispose older people to develop postchallenge hyperglycemia and type 2 diabetes. An improved understanding of the metabolic alterations associated with aging is essential for the development of preventive and therapeutic interventions in this population at high risk for glucose intolerance.

scholarly journals The INSPIRE Bio-resource Research Platform for Healthy Aging and Geroscience: Focus on the Human Translational Research Cohort (The INSPIRE-T Cohort)

2020 ◽  
pp. 1-11 ◽  
Author(s):  
S. Guyonnet ◽  
Y. Rolland ◽  
C. Takeda ◽  
P.-J. Ousset ◽  
I. Ader ◽  
...  
Keyword(s):  
Health Care ◽  
Translational Research ◽  
Healthy Aging ◽  
Care Pathway ◽  
Integrative Approach ◽  
Biological Aging ◽  
Imaging Data ◽  
Aging Research ◽  
Age Related

Background: The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. Objectives: The main objective of the INStitute for Prevention healthy agIng and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans. Methods: The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up. Expected Results: Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.

scholarly journals A ganglioside-based senescence-associated immune checkpoint

2021 ◽  
Author(s):  
Charlène Iltis ◽  
Laetitia Seguin ◽  
Ludovic Cervera ◽  
Lou Duret ◽  
Tynhinane Hamidouche ◽  
...  
Keyword(s):  
Immune System ◽  
Cellular Senescence ◽  
Immune Checkpoint ◽  
Healthy Aging ◽  
Immune Escape ◽  
Nk Cell ◽  
Senescent Cell ◽  
Therapeutic Interventions ◽  
Cell Functions ◽  
Age Related

Senescent cells accumulate in aging tissues, and their elimination can favor healthy aging1-4. Therefore, therapeutic interventions targeting cellular senescence may be promising strategies for delaying or reversing a vast range of age-related diseases5. As cells of the immune system are responsible for senescent cell elimination6-11, a possible anti-aging and pro-healthspan treatment is the specific activation of the immune system to induce senescent cell clearance. However, whether this elimination is limited by an immune checkpoint leading to tolerance of senescence cells is currently unknown. Here, we show that cellular senescence, elicited by various stressors other than oncogenic activation, triggers immune escape toward natural killer (NK) cells, which may thus limit the use of anti-senescence immunotherapies. Moreover, using mass spectrometry, we reveal that senescent cells reshuffle their glycosphingosine composition, toward a marked increase in the ganglioside content, including the appearance of disialylated ganglioside GD3. This senescence associated GD3 overexpression results from transcriptional upregulation of the gene encoding the enzyme ST8SIA1, which is responsible for GD3 synthesis. The high level of GD3 leads to a strong immunosuppressive signal affecting NK cell-mediated immunosurveillance. In a mouse model of lung fibrosis, senescent cell-dependent NK cell immunosuppression is blunted by in vivo administration of anti-GD3 monoclonal antibodies leading to a clear anti-fibrotic effect. These results demonstrate that GD3 upregulation in senescent cells drives a switch from immune clearance toward immune tolerance of senescent cells. Therefore, we propose that GD3 level acts as a senescence-associated immune checkpoint (SIC) that regulates NK cell functions toward senescent cells. Thus, targeting GD3 with specific antibodies may be a promising strategy for the development of effective anti-senescence immunotherapies.

Aging and cardioprotection

2007 ◽  
Vol 103 (6) ◽  
pp. 2120-2128 ◽  
Author(s):  
Arshad Jahangir ◽  
Sandeep Sagar ◽  
Andre Terzic
Keyword(s):  
Animal Models ◽  
Healthy Aging ◽  
Myocardial Dysfunction ◽  
Experimental Studies ◽  
Structural Heart Disease ◽  
The Elderly ◽  
Therapeutic Interventions ◽  
Limited Information ◽  
Aging Heart ◽  
Age Related

Advanced age is a strong independent predictor for death, disability, and morbidity in patients with structural heart disease. With the projected increase in the elderly population and the prevalence of age-related cardiovascular disabilities worldwide, the need to understand the biology of the aging heart, the mechanisms for age-mediated cardiac vulnerability, and the development of strategies to limit myocardial dysfunction in the elderly have never been more urgent. Experimental evidence in animal models indicate attenuation in cardioprotective pathways with aging, yet limited information is available regarding age-related changes in the human heart. Human cardiac aging generates a complex phenotype, only partially replicated in animal models. Here, we summarize current understanding of the aging heart stemming from clinical and experimental studies, and we highlight targets for protection of the vulnerable senescent myocardium. Further progress mandates assessment of human tissue to dissect specific aging-associated genomic and proteomic dynamics, and their functional consequences leading to increased susceptibility of the heart to injury, a critical step toward designing novel therapeutic interventions to limit age-related myocardial dysfunction and promote healthy aging.

scholarly journals Strategies to Prevent or Remediate Cancer and Treatment-Related Aging

2020 ◽  
Author(s):  
Jennifer L Guida ◽  
Tanya Agurs-Collins ◽  
Tim A Ahles ◽  
Judith Campisi ◽  
William Dale ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Healthy Aging ◽  
Care Delivery ◽  
Accelerated Aging ◽  
Adult Survivors ◽  
Therapeutic Interventions ◽  
Provider Education ◽  
Age Related ◽  
Optimal Dosing ◽  
Adult Cancer Survivors

Abstract Up to 85% of adult cancer survivors and 99% of adult survivors of childhood cancer live with an accumulation of chronic conditions, frailty, and/or cognitive impairments resulting from cancer and its treatment. Thus, survivors often show an accelerated development of multiple geriatric syndromes and need therapeutic interventions. To advance progress in this area, the National Cancer Institute convened the second of 2 think tanks under the auspices of the Cancer and Accelerated Aging: Advancing Research for Healthy Survivors initiative. Experts assembled to share evidence of promising strategies to prevent, slow, or reverse the aging consequences of cancer and its treatment. The meeting identified research and resource needs, including geroscience-guided clinical trials; comprehensive assessments of functional, cognitive, and psychosocial vulnerabilities to assess and predict age-related outcomes; preclinical and clinical research to determine the optimal dosing for behavioral (eg, diet, exercise) and pharmacologic (eg, senolytic) therapies; health-care delivery research to evaluate the efficacy of integrated cancer care delivery models; optimization of intervention implementation, delivery, and uptake; and patient and provider education on cancer and treatment-related late and long-term adverse effects. Addressing these needs will expand knowledge of aging-related consequences of cancer and cancer treatment and inform strategies to promote healthy aging of cancer survivors.

scholarly journals Analysis of the Impact of Selected Vitamins Deficiencies on the Risk of Disability in Older People

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3163
Author(s):  
Wassim Gana ◽  
Arnaud De Luca ◽  
Camille Debacq ◽  
Fanny Poitau ◽  
Pierre Poupin ◽  
...  
Keyword(s):  
Older People ◽  
Healthy Aging ◽  
Significant Risk ◽  
Nutritional Deficiencies ◽  
Nutritional Interventions ◽  
Vitamin Deficiencies ◽  
Nutrient Assimilation ◽  
Age Related ◽  
Poor Nutritional Status ◽  
The Impact

Vitamin deficiencies have a serious impact on healthy aging in older people. Many age-related disorders have a direct or indirect impact on nutrition, both in terms of nutrient assimilation and food access, which may result in vitamin deficiencies and may lead to or worsen disabilities. Frailty is characterized by reduced functional abilities, with a key role of malnutrition in its pathogenesis. Aging is associated with various changes in body composition that lead to sarcopenia. Frailty, aging, and sarcopenia all favor malnutrition, and poor nutritional status is a major cause of geriatric morbidity and mortality. In the present narrative review, we focused on vitamins with a significant risk of deficiency in high-income countries: D, C, and B (B6/B9/B12). We also focused on vitamin E as the main lipophilic antioxidant, synergistic to vitamin C. We first discuss the role and needs of these vitamins, the prevalence of deficiencies, and their causes and consequences. We then look at how these vitamins are involved in the biological pathways associated with sarcopenia and frailty. Lastly, we discuss the critical early diagnosis and management of these deficiencies and summarize potential ways of screening malnutrition. A focused nutritional approach might improve the diagnosis of nutritional deficiencies and the initiation of appropriate clinical interventions for reducing the risk of frailty. Further comprehensive research programs on nutritional interventions are needed, with a view to lowering deficiencies in older people and thus decreasing the risk of frailty and sarcopenia.

scholarly journals Transcriptome analysis reveals the difference between “healthy” and “common” aging and their connection with age-related diseases

2019 ◽  
Author(s):  
Lu Zeng ◽  
Jialiang Yang ◽  
Shouneng Peng ◽  
Jun Zhu ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Tissue Expression ◽  
Disease Genes ◽  
Gene Expressions ◽  
Protective Mechanisms ◽  
Aging Research ◽  
Age Related ◽  
The Difference ◽  
Project Data ◽  
Gene Regulations

AbstractA key goal of aging research is to understand mechanisms underlying healthy aging and use them to develop methods to promote the human healthspan. One approach is to identify gene regulations differentiating healthy aging from aging in the general population (i.e., “common” aging). In this study, we leveraged GTEx (Genotype-Tissue Expression) project data to investigate “healthy” and “common” aging in humans and their interconnection with diseases.We selected GTEx donors who were not annotated with diseases to approximate a “healthy” aging cohort. We then compared the age-associated genes derived from this cohort with age-associated genes from our “common” aging cohort which included all GTEx donors; we also compared the “healthy” and “common” aging gene expressions with various disease-associated gene expression to elucidate the relationships among “healthy”, “common” aging and disease. Our analyses showed that 1. “healthy” and “common” aging shared a large number of gene regulations; 2. Despite the substantial commonality, “healthy” and “common” aging genes also showed distinct function enrichment, and “common” aging genes had a higher enrichment for disease genes; 3. Disease-associated gene regulations were overall different from aging gene regulations. However, for genes regulated by both, their regulation directions were largely consistent, implying some aging processes could increase the susceptibility to disease development; and 4. Possible protective mechanisms were associated with the “healthy” aging gene regulations.In summary, our work highlights several unique features of human “healthy” aging program. This new knowledge can be used for the development of therapeutics to promote human healthspan.

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