DNA double-strand breaks: a potential therapeutic target for neurodegenerative diseases.

DNA double-strand breaks: a potential therapeutic target for neurodegenerative diseases. Chromosome Res. 2019 Nov 09;: Authors: Thadathil N, Hori R, Xiao J, Khan MM Abstract The complexity of neurodegeneration restricts the ability to understand and treat the neurological disorders affecting millions of people worldwide. Therefore, there is an unmet need to develop new and more effective therapeutic strategies to combat these devastating conditions and that will only be achieved with a better understanding of the biological mechanism associated with disease conditions. Recent studies highlight the role of DNA damage, particularly, DNA double-strand breaks (DSBs), in the progression of neuronal loss in a broad spectrum of human neurodegenerative diseases. This is not unexpected because neurons are prone to DNA damage due to their non-proliferative nature and high metabolic activity. However, it is not clear if DSBs is a primary driver of neuronal loss in disease conditions or simply occurs concomitant with disease progression. Here, we provide evidence that supports a critical role of DSBs in the pathogenesis of the neurodegenerative diseases. Among different kinds of DNA damages, DSBs are the most harmful and perilous type of DNA damage and can lead to cell death if left unrepaired or repaired with error. In this review, we explore the current state of knowledge regarding the role of DSBs repair mechanisms in preserving neuronal function and survival and...
Source: Chromosome Research - Category: Genetics & Stem Cells Authors: Tags: Chromosome Res Source Type: research

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In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, we show here that sEVs are responsible for mediating paracrine senescence and speculate that they could be involved in inducing bystander senescence during therapy-induced senescence or aging. In fact, when compared to soluble factors, sEVs have different biophysical and biochemical properties as they have a longer lifespan than do soluble factors and they are more resistant to protease degradation. The idea that blocking sEV secretion could be a potential therapeutic approach to alleviate senescence "spreading" during chemotherapy-induced senescence or in aging tissues presents itself as a very at...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, a significant (30%) increase in maximum lifespan of mice was found after nonablative transplantation of 100 million nucleated bone marrow (BM) cells from young donors, initiated at the age that is equivalent to 75 years for humans. Moreover, rejuvenation was accompanied by a high degree of BM chimerism for the nonablative approach. Six months after the transplantation, 28% of recipients' BM cells were of donor origin. The relatively high chimerism efficiency that we found is most likely due to the advanced age of our recipients having a depleted BM pool. In addition to the higher incorporation rates, ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusion and Future Aspects This review summarizes available NTF expression data, compiles existing evidence on the effects of glial NTF signaling in healthy conditions and in disease models (Figure 1), and highlights the importance of this topic for future studies. The relationship between NTFs and glia is crucial for both the developing and adult brain. While some of these factors, such as NT-3 and CNTF, have highly potent effects on gliogenesis, others like BDNF and GDNF, are important for glia-mediated synapse formation. Neurotrophic factors play significant roles during neurodegenerative disorders. In many cases, ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Silvia Pregnolato1*, Elavazhagan Chakkarapani1, Anthony R. Isles2 and Karen Luyt1 1Department of Neonatal Neurology, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom 2Behavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom Preterm birth complications are the leading cause of child death worldwide and a top global health priority. Among the survivors, the risk of life-long disabilities is high, including cerebral palsy and impairment of movement, cognition, and behavior. U...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusions In this review, we analyzed mechanisms through which mitobolites, a distinct set of mitochondria-generated metabolites, can be released from mitochondria and then act as second messengers that contribute to cellular and organismal aging by regulating longevity-defining processes outside of mitochondria. Our analysis indicates that in eukaryotes across phyla, these second messengers of cellular aging exhibit the following common features: (1) they are produced in mitochondria in response to certain changes in the nutrient, stress, proliferation or age status of the cell; it remains unknown, however, what kind o...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we show that calorie restriction is protective against age-related increases in senescence and microglia activation and pro-inflammatory cytokine expression in an animal model of aging. Further, these protective effects mitigated age-related decline in neuroblast and neuronal production, and enhanced olfactory memory performance, a behavioral index of neurogenesis in the SVZ. Our results support the concept that calorie restriction might be an effective anti-aging intervention in the context of healthy brain aging. Greater Modest Activity in Late Life Correlates with Lower Incidence of Dementia ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, this is the first report to show that pyroptotic cell death occurs in the aging brain and that the inflammasome can be a viable target to decrease the oxidative stress that occurs as a result of aging. Reducing Levels of Protein Manufacture Slows Measures of Aging in Nematodes https://www.fightaging.org/archives/2018/12/reducing-levels-of-protein-manufacture-slows-measures-of-aging-in-nematodes/ Researchers here demonstrate that an antibiotic slows aging in nematode worms, providing evidence for it to work through a reduction in protein synthesis. Beyond a slowing of aging, one of the con...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we found that TXNIP deficiency induces accelerated senescent phenotypes of mouse embryonic fibroblast (MEF) cells under high glucose condition and that the induction of cellular ROS or AKT activation is critical for cellular senescence. Our results also revealed that TXNIP inhibits AKT activity by a direct interaction, which is upregulated by high glucose and H2O2 treatment. In addition, TXNIP knockout mice exhibited an increase in glucose uptake and aging-associated phenotypes including a decrease in energy metabolism and induction of cellular senescence and aging-associated gene expression. We propose that...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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