scholarly journals Impact of telomerase ablation on organismal viability, aging, and tumorigenesis in mice lacking the DNA repair proteins PARP-1, Ku86, or DNA-PKcs

2004 ◽  
Vol 167 (4) ◽  
pp. 627-638 ◽  
Author(s):  
Silvia Espejel ◽  
Peter Klatt ◽  
Josiane Ménissier-de Murcia ◽  
Juan Martín-Caballero ◽  
Juana M. Flores ◽  
...  
Keyword(s):  
Dna Repair ◽  
Aging Process ◽  
Telomere Shortening ◽  
Age Related ◽  
Dna Repair Proteins ◽  
Telomere Function ◽  
Telomere Capping ◽  
The Impact ◽  
Parp 1 ◽  
Deficient Mice

The DNA repair proteins poly(ADP-ribose) polymerase-1 (PARP-1), Ku86, and catalytic subunit of DNA-PK (DNA-PKcs) have been involved in telomere metabolism. To genetically dissect the impact of these activities on telomere function, as well as organismal cancer and aging, we have generated mice doubly deficient for both telomerase and any of the mentioned DNA repair proteins, PARP-1, Ku86, or DNA-PKcs. First, we show that abrogation of PARP-1 in the absence of telomerase does not affect the rate of telomere shortening, telomere capping, or organismal viability compared with single telomerase-deficient controls. Thus, PARP-1 does not have a major role in telomere metabolism, not even in the context of telomerase deficiency. In contrast, mice doubly deficient for telomerase and either Ku86 or DNA-PKcs manifest accelerated loss of organismal viability compared with single telomerase-deficient mice. Interestingly, this loss of organismal viability correlates with proliferative defects and age-related pathologies, but not with increased incidence of cancer. These results support the notion that absence of telomerase and short telomeres in combination with DNA repair deficiencies accelerate the aging process without impacting on tumorigenesis.

scholarly journals The Impact of Behavioral Intervention on Obesity Mediated Declines in Mobility Function: Implications for Longevity

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Joe Nocera ◽  
Thomas W. Buford ◽  
Todd M. Manini ◽  
Kelly Naugle ◽  
Christiaan Leeuwenburgh ◽  
...  
Keyword(s):  
Older Adults ◽  
Aging Process ◽  
Strong Predictor ◽  
Functional Limitations ◽  
Mobility Performance ◽  
Mobility Function ◽  
Age Related ◽  
Close Relationship ◽  
Primary Focus ◽  
The Impact

A primary focus of longevity research is to identify prognostic risk factors that can be mediated by early treatment efforts. To date, much of this work has focused on understanding the biological processes that may contribute to aging process and age-related disease conditions. Although such processes are undoubtedly important, no current biological intervention aimed at increasing health and lifespan exists. Interestingly, a close relationship between mobility performance and the aging process has been documented in older adults. For example, recent studies have identified functional status, as assessed by walking speed, as a strong predictor of major health outcomes, including mortality, in older adults. This paper aims to describe the relationship between the comorbidities related to decreased health and lifespan and mobility function in obese, older adults. Concurrently, lifestyle interventions, including diet and exercise, are described as a means to improve mobility function and thereby limit the functional limitations associated with increased mortality.

Human PARP-1 knock-in mice: A novel model to study the impact of improved DNA repair capacity on mammalian longevity

2007 ◽  
Vol 42 (1-2) ◽  
pp. 143
Author(s):  
A. Mangerich ◽  
J. Diefenbach ◽  
U. Kloz ◽  
F. van der Hoeven ◽  
A. Bürkle
Keyword(s):  
Dna Repair ◽  
Repair Capacity ◽  
Dna Repair Capacity ◽  
The Impact ◽  
Parp 1 ◽  
Novel Model

scholarly journals Role of Mammalian Rad54 in Telomere Length Maintenance

2003 ◽  
Vol 23 (16) ◽  
pp. 5572-5580 ◽  
Author(s):  
Isabel Jaco ◽  
Purificación Muñoz ◽  
Fermín Goytisolo ◽  
Joanna Wesoly ◽  
Susan Bailey ◽  
...  
Keyword(s):  
Dna Repair ◽  
Telomere Length ◽  
Essential Role ◽  
Repair Pathway ◽  
Wild Type ◽  
Putative Role ◽  
Telomere Capping ◽  
Chromosome Fusions ◽  
Deficient Mice

ABSTRACT The homologous recombination (HR) DNA repair pathway participates in telomere length maintenance in yeast but its putative role at mammalian telomeres is unknown. Mammalian Rad54 is part of the HR machinery, and Rad54-deficient mice show a reduced HR capability. Here, we show that Rad54-deficient mice also show significantly shorter telomeres than wild-type controls, indicating that Rad54 activity plays an essential role in telomere length maintenance in mammals. Rad54 deficiency also resulted in an increased frequency of end-to-end chromosome fusions involving telomeres compared to the controls, suggesting a putative role of Rad54 in telomere capping. Finally, the study of mice doubly deficient for Rad54 and DNA-PKcs showed that telomere fusions due to DNA-PKcs deficiency were not rescued in the absence of Rad54, suggesting that they are not mediated by Rad54 activity.

scholarly journals COVID-19 in Joint Ageing and Osteoarthritis: Current Status and Perspectives

2022 ◽  
Vol 23 (2) ◽  
pp. 720
Author(s):  
Marianne Lauwers ◽  
Manting Au ◽  
Shuofeng Yuan ◽  
Chunyi Wen
Keyword(s):  
Adipose Tissue ◽  
Aging Process ◽  
Current Knowledge ◽  
Calcium Deficiency ◽  
Musculoskeletal Symptoms ◽  
Current Status ◽  
Musculoskeletal Tissue ◽  
Age Related ◽  
The Impact

COVID-19 is a trending topic worldwide due to its immense impact on society. Recent trends have shifted from acute effects towards the long-term morbidity of COVID-19. In this review, we hypothesize that SARS-CoV-2 contributes to age-related perturbations in endothelial and adipose tissue, which are known to characterize the early aging process. This would explain the long-lasting symptoms of SARS-CoV-2 as the result of an accelerated aging process. Connective tissues such as adipose tissue and musculoskeletal tissue are the primary sites of aging. Therefore, current literature was analyzed focusing on the musculoskeletal symptoms in COVID-19 patients. Hypovitaminosis D, increased fragility, and calcium deficiency point towards bone aging, while joint and muscle pain are typical for joint and muscle aging, respectively. These characteristics could be classified as early osteoarthritis-like phenotype. Exploration of the impact of SARS-CoV-2 and osteoarthritis on endothelial and adipose tissue, as well as neuronal function, showed similar perturbations. At a molecular level, this could be attributed to the angiotensin-converting enzyme 2 expression, renin-angiotensin system dysfunction, and inflammation. Finally, the influence of the nicotinic cholinergic system is being evaluated as a new treatment strategy. This is combined with the current knowledge of musculoskeletal aging to pave the road towards the treatment of long-term COVID-19.

scholarly journals MicroRNAs Modulate Oxidative Stress in Hypertension through PARP-1 Regulation

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Douglas F. Dluzen ◽  
Yoonseo Kim ◽  
Paul Bastian ◽  
Yongqing Zhang ◽  
Elin Lehrmann ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Cell Survival ◽  
Oxidative Dna Damage ◽  
White Women ◽  
Luciferase Reporter ◽  
Coding Region ◽  
Age Related ◽  
Parp 1

Oxidative stress is thought to contribute to aging and age-related diseases, such as cardiovascular and neurodegenerative diseases, and is a risk factor for systemic arterial hypertension. Previously, we reported differential mRNA and microRNA (miRNA) expression between African American (AA) and white women with hypertension. Here, we found that the poly-(ADP-ribose) polymerase 1 (PARP-1), a DNA damage sensor protein involved in DNA repair and other cellular processes, is upregulated in AA women with hypertension. To explore this mechanism, we identified two miRNAs, miR-103a-2-5p and miR-585-5p, that are differentially expressed with hypertension and were predicted to target PARP1. Through overexpression of each miRNA-downregulated PARP-1 mRNA and protein levels and using heterologous luciferase reporter assays, we demonstrate that miR-103a-2-5p and miR-585-5p regulate PARP1 through binding within the coding region. Given the important role of PARP-1 in DNA repair, we assessed whether overexpression of miR-103a-2-5p or miR-585-5p affected DNA damage and cell survival. Overexpression of these miRNAs enhanced DNA damage and decreased both cell survival and colony formation. These findings highlight the role for PARP-1 in regulating oxidative DNA damage in hypertension and identify important new miRNA regulators of PARP-1 expression. These insights may provide additional avenues to understand hypertension health disparities.

scholarly journals Age-related dystrophic changes in corneal endothelium from DNA repair-deficient mice

Aging Cell ◽  
2013 ◽  
Vol 12 (6) ◽  
pp. 1122-1131 ◽  
Author(s):  
Danny S. Roh ◽  
Yiqin Du ◽  
Michelle L. Gabriele ◽  
Andria R. Robinson ◽  
Laura J. Niedernhofer ◽  
...  
Keyword(s):  
Dna Repair ◽  
Corneal Endothelium ◽  
Age Related ◽  
Deficient Mice

Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 517-520 ◽  
Author(s):  
Richard C. Allsopp ◽  
Gregg B. Morin ◽  
Ronald DePinho ◽  
Calvin B. Harley ◽  
Irving L. Weissman
Keyword(s):  
Replicative Capacity ◽  
Wild Type ◽  
Hematopoietic Progenitors ◽  
Telomere Shortening ◽  
Hematopoietic Stem ◽  
Telomere Function ◽  
Deficient Mice ◽  
Serial Transplantation

Abstract Telomere shortening ultimately limits the replicative life span of cultured human somatic cells. Telomeres also shorten during replicative aging in vivo in hematopoietic cells, including early hematopoietic progenitors and hematopoietic stem cells (HSCs), from humans and mice, despite readily detectable levels of telomerase in these cells. To assess the relevance of telomerase to the long-term replicative capacity of HSCs in vivo, we serially transplanted HSCs from wild-type and telomerase-deficient mice until exhaustion and monitored telomere length in HSCs during this process. Telomerase-deficient HSCs could be serially transplanted for only 2 rounds, whereas wild-type HSCs could be serially transplanted for at least 4 rounds. Furthermore, the rate of telomere shortening was increased approximately 2-fold during serial transplantation of telomerase-deficient HSCs. These findings suggest that one role for telomerase in the HSC is to partially counter the rate of telomere shortening during division of HSCs, thereby preventing premature loss of telomere function and providing added replicative capacity.

scholarly journals Trends in Natural Nutrients for Oxidative Stress and Cell Senescence

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Navid Omidifar ◽  
Mohsen moghadami ◽  
Seyyed Mojtaba Mousavi ◽  
Seyyed Alireza Hashemi ◽  
Ahmad Gholami ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Olive Oil ◽  
Disease Progression ◽  
Dietary Patterns ◽  
Aging Process ◽  
Cell Senescence ◽  
Telomere Shortening ◽  
Age Related ◽  
Dietary Components ◽  
Underlying Mechanisms

Due to the increase in the aged population and increased life expectancy, the underlying mechanisms involved in the aging process and cell senescence and the ways for modulating these processes in age-related diseases become important. One of the main mechanisms involved in aging and cell senescence, especially in the diseases related to aging, is the oxidative stress process and the following inflammation. Hence, the effects of antioxidants are highlighted in the literature due to their beneficial impacts on inhibiting telomere shortening or DNA damage and other processes related to aging and cell senescence in age-related diseases. Dietary components, foods, and dietary patterns rich in antioxidants can modulate the aging process and delay the progression of some chronic diseases such as cardiovascular diseases, diabetes, and Alzheimer’s disease. Foods high in polyphenols, vitamin C, or carotenoids, olive oil, seeds, nuts, legumes, dietary supplements such as CoQ10, and some other dietary factors are the most important nutritional sources that have high antioxidant contents which can positively affect cell senescence and disease progression. Plant dietary patterns including Mediterranean diets can also inhibit telomere shortening following oxidative damages, and this can delay cell aging and senescence in age-related diseases. Further, olive oil can inhibit protein aggregation in Alzheimer’s disease. It can be concluded that nutrition can delay the process of cell senescence in age-related diseases via inhibiting oxidative and inflammatory pathways. However, more studies are needed to better clarify the underlying mechanisms of nutrition and dietary components on cell senescence, aging, and disease progression, especially those related to age.

Inflammation in Aging Part 1: Physiology and Immunological Mechanisms

2009 ◽  
Vol 11 (3) ◽  
pp. 245-252 ◽  
Author(s):  
Katherine J. Hunt ◽  
Bronagh M. Walsh ◽  
David Voegeli ◽  
Helen C. Roberts
Keyword(s):  
Chronic Inflammation ◽  
Aging Process ◽  
Age Related ◽  
Immunological Mechanisms ◽  
Inflammatory Processes ◽  
Inflammatory Proteins ◽  
The Individual ◽  
Inflammatory Milieu ◽  
The Impact

During the aging process, remodeling of several body systems occurs, and these changes can have a startling effect upon the immune system. The reduction in sex steroids and growth hormones and declines in vitamin D concentration that accompany the aging process are associated with increases in the baseline levels of inflammatory proteins. At the same time, inflammation arising from atherosclerosis and other chronic diseases further contributes to the inflammatory milieu and effects a state of chronic inflammation. This chronic inflammation, or ‘‘inflammaging’’ as it has been termed, seems to be associated with a host of adverse effects contributing to many of the health problems that increase morbidity and decrease both quality of life and the ability to maintain independence in old age. For nurses to be truly informed when caring for older people and to ensure that they have a detailed understanding of the complexities of older people’s health needs, they must have a knowledge of the physiological and immunological changes with age. This is the first of a two-part article on inflammatory processes in aging. These age-related changes are presented here, including an examination of the impact of genetic and lifestyle factors. The effect of these changes on the health of the individual and implications for practice are described in Part 2.

Sign in / Sign up

Export Citation Format

Share Document