scholarly journals Physical Indicators of Aging are Related to Cellular Senescence Signal P16INK4a in Midlife Adults

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 1022-1022
Author(s):  
Kelly Rentscher ◽  
Teresa Seeman ◽  
Steve Cole ◽  
Judith Carroll
Keyword(s):  
Cellular Senescence ◽  
Whole Blood ◽  
Frailty Index ◽  
The United States ◽  
Daily Activities ◽  
Biological Aging ◽  
Biomarkers Of Aging ◽  
Age Related ◽  
And Performance ◽  
Midlife Adults

Abstract Cellular senescence signal p16INK4a has been identified as a biomarker of aging that accumulates with chronological age across several tissues in mice and humans and may be potentially modifiable by interventions. This study examined whether physical indicators of aging were associated with p16INK4a and other markers of the aging process in midlife adults. Participants were 543 adults aged 26–78 years (Mage=54.0; 50.5% female) in the Midlife in the United States Refresher cohort. Interviews, questionnaires, and performance tests measured physical indicators of aging, including the Fried frailty index, limitations in daily activities, and age-related comorbidities. RNA sequencing of whole blood assessed biomarkers of aging: p16INK4a (CDKN2A), the DNA damage response (DDR), and the senescence-associated secretory phenotype (SASP). Older age was associated with enhanced p16INK4a (r=.11, p=.01), DDR (r=.34, p<.001), and SASP (r=.38, p<.001) expression. Multiple regression models that adjusted for age, sex, race/ethnicity, BMI, comorbidities, and time between assessments revealed that frailty (pre-frail/frail vs. non-frail) was associated with greater p16INK4a (B=0.13, p=.048) and marginally greater DDR (B=0.06, p=.06) expression. Limitations in daily activities were also associated with p16INK4a (B=0.12, p=.045). History of heart disease, stroke, arthritis, and cancer were associated with DDR and SASP expression in unadjusted models only (ps<.05). In summary, senescence indicator p16INK4a was elevated in whole blood samples from middle-aged adults who showed signs of frailty and limitations in daily activities. Findings suggest that whole blood p16INK4a expression might potentially be used to detect early signs of aging and target interventions to reduce biological aging and frailty.

Individual DNA Methylation Profile is Correlated with Age and can be Targeted to Modulate Healthy Aging and Longevity

2019 ◽  
Vol 25 (39) ◽  
pp. 4139-4149 ◽  
Author(s):  
Francesco Guarasci ◽  
Patrizia D'Aquila ◽  
Alberto Montesanto ◽  
Andrea Corsonello ◽  
Dina Bellizzi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Aging Process ◽  
Healthy Aging ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Biological Aging ◽  
Biomarkers Of Aging ◽  
Age Related

: Patterns of DNA methylation, the best characterized epigenetic modification, are modulated by aging. In humans, different studies at both site-specific and genome-wide levels have reported that modifications of DNA methylation are associated with the chronological aging process but also with the quality of aging (or biological aging), providing new perspectives for establishing powerful biomarkers of aging. : In this article, the role of DNA methylation in aging and longevity has been reviewed by analysing literature data about DNA methylation variations occurring during the lifetime in response to environmental factors and genetic background, and their association with the aging process and, in particular, with the quality of aging. Special attention has been devoted to the relationship between nuclear DNA methylation patterns, mitochondrial DNA epigenetic modifications, and longevity. Mitochondrial DNA has recently been reported to modulate global DNA methylation levels of the nuclear genome during the lifetime, and, in spite of the previous belief, it has been found to be the target of methylation modifications. : Analysis of DNA methylation profiles across lifetime shows that a remodeling of the methylome occurs with age and/or with age-related decline. Thus, it can be an excellent biomarker of aging and of the individual decline and frailty status. The knowledge about the mechanisms underlying these modifications is crucial since it might allow the opportunity for targeted treatment to modulate the rate of aging and longevity.

Emerging Technologies for Aging in Place

2008 ◽  
pp. 513-518
Author(s):  
Shirley Ann Becker ◽  
Frank Webbe
Keyword(s):  
United States ◽  
Emerging Technologies ◽  
Healthcare Delivery ◽  
The United States ◽  
Assistive Technologies ◽  
Daily Activities ◽  
Health Conditions ◽  
Age Related ◽  
United States Economy ◽  
Health Related

Similar to other nations, the United States faces a critical challenge in dealing with an aging population that has unprecedented life expectancies. Emerging technologies offer the hope of allowing older adults to remain in their homes longer by empowering individuals to manage daily activities while dealing with chronic health conditions and age-related diseases. These technologies increasingly target a home environment whereby on a regular basis an individual can obtain assistance in performing daily living activities, stay connected to family and friends, manage medication, and be monitored for health-related changes. As important as these assistive technologies are for individuals and families, their potential for positively impacting the United States economy by changing the model of healthcare delivery is equally huge.

Periodontitis and Accelerated Biological Aging: A Geroscience Approach

2021 ◽  
pp. 002203452110379
Author(s):  
G. Baima ◽  
M. Romandini ◽  
F. Citterio ◽  
F. Romano ◽  
M. Aimetti
Keyword(s):  
Cellular Senescence ◽  
Tooth Loss ◽  
Alveolar Bone ◽  
Epidemiological Data ◽  
Health Concern ◽  
Chronological Age ◽  
Biological Aging ◽  
Intermittent Fasting ◽  
Chronic Hyperglycemia ◽  
Age Related

As the whole world is epidemically aging, the burden of periodontitis and tooth loss is becoming a major health concern. Growing meta-epidemiological data implicate chronic systemic inflammation/infection due to periodontitis as an independent risk factor for aging-related diseases and mortality. However, because people age differently, chronological age is not a reliable marker of an individual’s functional status. Recent advances in geroscience have shown that various biomarker signatures of biological aging are longitudinally associated with declined physical function, morbidity, and mortality due to major age-related diseases, including periodontitis. Here, we emphasize novel research developments bidirectionally linking periodontitis to accelerated biological aging. Using a composite biomarker age estimator, a striking increase in periodontitis and tooth loss was observed in subjects whose biological age at baseline was higher than their chronological age. Moreover, significantly shortened telomeres were encountered in populations affected by severe periodontitis. Second, we elucidate the cellular and molecular pillars of the aging process at the periodontal level. Accumulating evidence suggests that cellular senescence, stem cell exhaustion, and immunoaging are hallmarks of biological aging implicated in the impairment of periodontal homeostasis and the pathophysiology of periodontitis. Indeed, persistent bacteria-derived lipopolysaccharide stimulation influences cellular senescence in osteocytes, driving alveolar bone resorption. Moreover, inflammaging status induced by chronic hyperglycemia elevates the burden of senescent cells in gingival tissues, impairing their barrier function. Lastly, we reviewed a recent breakthrough in senotherapy to directly target the mechanisms of aging at the periodontal level. Physical exercise and intermittent fasting, together with natural compounds, senolytic drugs, and cell therapy, are increasingly being evaluated to rejuvenate the oral cavity. Following these innovations in geroscience, further advancements could provide oral clinicians the chance to intercept biological aging when still “subclinical” and set interventions for halting or delaying the trajectory toward aging-related diseases while patients are still chronologically young.

scholarly journals BIOMARKER STRATEGIES FOR GEROSCIENCE-GUIDED CLINICAL TRIALS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S745-S746
Author(s):  
Jamie N Justice ◽  
George A Kuchel ◽  
Nir Barzilai ◽  
Stephen Kritchevsky
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Biological Aging ◽  
Expert Committee ◽  
Biomarkers Of Aging ◽  
Age Related ◽  
Trial Outcomes ◽  
Biology Of Aging ◽  
Potential Use ◽  
Selection Of

Abstract Significant progress in the biology of aging and animal models supports the geroscience hypothesis: by targeting biological aging the onset of age-related diseases can be delayed. Geroscience investigators will test this hypothesis in a multicenter clinical trial, to determine if interventions on biological aging processes can prevent accumulation of multiple age-related diseases and aging phenotypes in older adults. Prodigious activity is underway to develop markers of biological aging, but currently there is no aging biomarker consensus to support geroscience-guided clinical trial outcomes. We convened an expert committee to establish a framework for selection of blood-based biomarkers, emphasizing: feasibility/reliability; aging relevance; ability to predict clinical trial outcomes; and responsiveness to intervention. We applied this framework and identified a short-list of blood-based biomarkers with potential use in multicenter trials on aging. We review progress on efforts to test these candidate biomarkers of aging and development of biomarkers strategy for geroscience-guided clinical trials.

scholarly journals Gut Microbiome and Cellular Senescence in the Context of Aging and Disease: An Emerging Frontier

2021 ◽  
Author(s):  
Rohit Sharma
Keyword(s):  
Gut Microbiota ◽  
Cellular Senescence ◽  
Gut Microbiome ◽  
Biological Aging ◽  
Future Research ◽  
Age Related ◽  
Integrative View ◽  
Health And Disease ◽  
Molecular Aspects ◽  
Relationship Of

The significance of diversity, composition, and functional attributes of the gut microbiota is recognized in human health and disease. Studies have also shown that the gut microbiota is related to human aging, and a causal relationship between gut microflora dysbiosis and chronic age-related disorders is also becoming apparent. Further, emerging evidence indicates that age-associated changes in the gut microbiome are predictors of human survival and longevity. Recent advances in our understanding of the cellular and molecular aspects of biological aging have revealed a cellular senescence-centric view of the aging process. However, the association between gut microbiome and cellular senescence is only beginning to be understood. The present review provides an integrative view of the emerging relationship between the gut microbiome and cellular senescence in aging and disease. Evidence relating to microbiome-mediated modulation of senescent cells, as well as senescent cells-mediated changes in intestinal homeostasis have been discussed. Unanswered questions and future research directions have also been deliberated to truly ascertain the relationship of the gut microbiome and cellular senescence for developing microbiome-based age-delaying and longevity promoting therapies.

scholarly journals Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives

2021 ◽  
Vol 11 ◽  
Author(s):  
Alexander Vaiserman ◽  
Dmytro Krasnienkov
Keyword(s):  
Telomere Length ◽  
State Of The Art ◽  
Frailty Index ◽  
Biological Age ◽  
Epigenetic Clock ◽  
Telomere Attrition ◽  
Immune Parameters ◽  
Biomarkers Of Aging ◽  
Age Related ◽  
Research Findings

Telomere shortening is a well-known hallmark of both cellular senescence and organismal aging. An accelerated rate of telomere attrition is also a common feature of age-related diseases. Therefore, telomere length (TL) has been recognized for a long time as one of the best biomarkers of aging. Recent research findings, however, indicate that TL per se can only allow a rough estimate of aging rate and can hardly be regarded as a clinically important risk marker for age-related pathologies and mortality. Evidence is obtained that other indicators such as certain immune parameters, indices of epigenetic age, etc., could be stronger predictors of the health status and the risk of chronic disease. However, despite these issues and limitations, TL remains to be very informative marker in accessing the biological age when used along with other markers such as indices of homeostatic dysregulation, frailty index, epigenetic clock, etc. This review article is aimed at describing the current state of the art in the field and at discussing recent research findings and divergent viewpoints regarding the usefulness of leukocyte TL for estimating the human biological age.

scholarly journals p16-3MR: a novel model to study cellular senescence in cigarette smoke-induced lung injuries during aging

2021 ◽  
Author(s):  
Irfan Rahman ◽  
Gagandeep Kaur ◽  
Isaac Sundar
Keyword(s):  
Cigarette Smoke ◽  
Cellular Senescence ◽  
Biological Aging ◽  
In Vivo Model ◽  
Chronic Obstructive ◽  
Suitable Model ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Chronic Smoking

Abstract Cellular senescence and lung aging are associated with the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). COPD progresses with aging, and chronic smoking is the key susceptibility factor in lung pathological changes concurrent with biological aging. However, these processes involving cigarette smoke (CS)-mediated lung cellular senescence are difficult to distinguish. One of the impediments to study cellular senescence in relation to age-related lung pathologies is the lack of a suitable in vivo model. In view of this, we provide evidence that supports the suitability of p16-3MR mice to study cellular senescence in CS-mediated and age-related lung pathologies. p16-3MR mice has a trimodal reporter fused to the promoter of p16INK4a gene that enables detection, isolation and selective elimination of senescent cells, thus making it a suitable model to study cellular senescence. To determine its suitability in CS-mediated lung pathologies, we exposed young (12-14 months) and old (17-20 months) p16-3MR mice to 30-day CS exposure and studied the expression of senescent genes (p16, p21 and p53) and SASP-associated markers (MMP9, MMP12, PAI-1, and FN-1) in air- and CS-exposed mouse lungs. Our results showed that this model could detect cellular senescence using luminescence and isolate cells undergoing senescence with the help of tissue fluorescence in CS-challenged young and old mice. Our results from the expression of senescence markers and SASP-associated genes in CS-challenged young and old p16-3MR mice were comparable with increased lung cellular senescence and SASP in COPD. We further showed age-dependent alteration in the (i) tissue luminescence and fluorescence, (ii) mRNA and protein expressions of senescent markers and SASP genes, and (iii) SA-β-gal activity in CS-challenged young and old p16-3MR mice as compared to their air controls. Overall, we showed that p16-3MR is a competent model to study cellular senescence in age-related pathologies and could help understand the pathobiology of cellular senescence in lung conditions like COPD and fibrosis.

scholarly journals Biological age is a universal marker of aging, stress, and frailty

2019 ◽  
Author(s):  
Timothy V. Pyrkov ◽  
Peter O. Fedichev
Keyword(s):  
Large Scale ◽  
Systematic Investigation ◽  
Biological Age ◽  
Biological Aging ◽  
Physical And Mental Health ◽  
Mortality And Morbidity ◽  
Markers Of Inflammation ◽  
Biomarkers Of Aging ◽  
Age Related

SummaryWe carried out a systematic investigation of supervised learning techniques for biological age modeling. The biological aging acceleration is associated with the remaining health- and life-span. Artificial Deep Neural Networks (DNN) could be used to reduce the error of chronological age predictors, though often at the expense of the ability to distinguish health conditions. Mortality and morbidity hazards models based on survival follow-up data showed the best performance. Alternatively, logistic regression trained to identify chronic diseases was shown to be a good approximation of hazards models when data on survival follow-up times were unavailable. In all models, the biological aging acceleration was associated with disease burden in persons with diagnosed chronic age-related conditions. For healthy individuals, the same quantity was associated with molecular markers of inflammation (such as C-reactive protein), smoking, current physical, and mental health (including sleeping troubles, feeling tired or little interest in doing things). The biological age thus emerged as a universal biomarker of age, frailty and stress for applications involving large scale studies of the effects of longevity drugs on risks of diseases and quality of life.To be published as Chapter 2 in “Biomarkers of aging”, ed. A. Moskalev, Springer, 2019.

Emerging Technologies for Aging in Place

2011 ◽  
pp. 2047-2053
Author(s):  
Shirley Ann Becker ◽  
Frank Webbe
Keyword(s):  
United States ◽  
Emerging Technologies ◽  
Healthcare Delivery ◽  
The United States ◽  
Assistive Technologies ◽  
Daily Activities ◽  
Health Conditions ◽  
Age Related ◽  
United States Economy ◽  
Health Related

Similar to other nations, the United States faces a critical challenge in dealing with an aging population that has unprecedented life expectancies. Emerging technologies offer the hope of allowing older adults to remain in their homes longer by empowering individuals to manage daily activities while dealing with chronic health conditions and age-related diseases. These technologies increasingly target a home environment whereby on a regular basis an individual can obtain assistance in performing daily living activities, stay connected to family and friends, manage medication, and be monitored for health-related changes. As important as these assistive technologies are for individuals and families, their potential for positively impacting the United States economy by changing the model of healthcare delivery is equally huge.

scholarly journals p16-3MR: a novel model to study cellular senescence in cigarette smoke-induced lung injuries during aging

2021 ◽  
Author(s):  
Gagandeep Kaur ◽  
Isaac K. Sundar ◽  
Irfan Rahman
Keyword(s):  
Cigarette Smoke ◽  
Cellular Senescence ◽  
Biological Aging ◽  
Chronic Obstructive ◽  
Suitable Model ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Lung Injuries ◽  
Chronic Smoking

ABSTRACTCellular senescence and lung aging are associated with the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). COPD progresses with aging, and chronic smoking is the key susceptibility factor in lung pathological changes concurrent with biological aging. However, these processes involving cigarette smoke (CS)-mediated lung cellular senescence are difficult to distinguish. One of the impediments to study cellular senescence in relation to age-related lung pathologies is the lack of a suitable in vivo model. In view of this, we provide evidence that supports the suitability of p16-3MR mice to study cellular senescence in CS-mediated and age-related lung pathologies. p16-3MR mice has a trimodal reporter fused to the promoter of p16INK4a gene that enables detection, isolation and selective elimination of senescent cells, thus making it a suitable model to study cellular senescence. To determine its suitability in CS-mediated lung pathologies, we exposed young (12-14 months) and old (17-20 months) p16-3MR mice to 30-day CS exposure and studied the expression of senescent genes (p16, p21 and p53) and SASP-associated markers (MMP9, MMP12, PAI-1, and FN-1) in air- and CS-exposed mouse lungs. Our results showed that this model could detect cellular senescence using luminescence and isolate cells undergoing senescence with the help of tissue fluorescence in CS-challenged young and old mice. Our results from the expression of senescence markers and SASP-associated genes in CS-challenged young and old p16-3MR mice were comparable with increased lung cellular senescence and SASP in COPD. We further showed age-dependent alteration in the (i) tissue luminescence and fluorescence, (ii) mRNA and protein expressions of senescent markers and SASP genes, and (iii) SA-β-gal activity in CS-challenged young and old p16-3MR mice as compared to their air controls. Overall, we showed that p16-3MR is a competent model to study cellular senescence in age-related pathologies and could help understand the pathobiology of cellular senescence in lung conditions like COPD and fibrosis.

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