Mitophagy and DNA Damage Signaling in Human Aging

Publication date: Available online 7 January 2020Source: Mechanisms of Ageing and DevelopmentAuthor(s): Mansi Babbar, Sambuddha Basu, Beimeng Yang, Deborah L. Croteau, Vilhelm A. BohrAbstractAging is associated with multiple human pathologies. In the past few years mitochondrial homeostasis has been well corelated with age-related disorders and longevity. Mitochondrial homeostasis involves generation, biogenesis and removal of dysfunctional mitochondria via mitophagy. Mitophagy is regulated by various mitochondrial and extra-mitochondrial factors including morphology, oxidative stress and DNA damage. For decades, DNA damage and inefficient DNA repair have been considered major determinants for age-related disorders. Although defects in DNA damage recognition and repair and mitophagy are well documented to be major factors in age-associated diseases, interactivity between these is poorly understood. Mitophagy efficiency decreases with age leading to accumulation of dysfunctional mitochondria enhancing the severity of age-related disorders including neurodegenerative diseases, inflammatory diseases, cancer, diabetes and many more. Therefore, mitophagy is being targeted for intervention in age-associated disorders. NAD+ supplementation has emerged as one intervention to target both defective DNA repair and mitophagy. In this review, we discuss the molecular signaling pathways involved in regulation of DNA damage and repair and of mitophagy, and we highlight the opportunities for...
Source: Mechanisms of Ageing and Development - Category: Geriatrics Source Type: research

Related Links:

In conclusion, our results suggest a previously unknown mechanism whereby the canonical NF-κB cascade and a mitochondrial fission pathway interdependently regulate endothelial inflammation. Lin28 as a Target for Nerve Regeneration https://www.fightaging.org/archives/2020/05/lin28-as-a-target-for-nerve-regeneration/ Researchers here show that the gene Lin28 regulates axon regrowth. In mice, raised levels of Lin28 produce greater regeneration of nerve injuries. Past research has investigated Lin28 from the standpoint of producing a more general improvement in regenerative capacity. It improves mitoch...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function. On Nutraceutical Senolytics https://www.fightaging.org/archives/2020/05/on-nutraceutical-senolytics/ Nutraceuticals are compounds derived from foods, usually plants. In principle one can find useful therapies in the natural world, taking the approach of identifying interesting molecules and refining them to a greater potency than naturally occurs in order to produce a usefully large therape...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we found that older nematodes have higher ROS levels. Interestingly, after hydrogen treatment, the ROS levels were significantly decreased, and hydrogen could significantly extend the lifespans of the N2, sod-3 and sod-5 mutant strains, by approximately 22.7%, 9.5%, and 8.7%, respectively. In addition, aging is regulated by a variety of pathways, such as the insulin signaling pathway, the rapamycin target signaling pathway, and the caloric restriction pathway. However, our results showed that the lifespans of the daf-2 and daf-16 strains, in which these pathways are upregulated, were not affected afte...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The objective is to start treating chronic diseases from the root and not the symptoms of the disease. As we are starting to enroll patients in "senolytics-clinical trials," it will be imperative to assess if senolysis efficiently targets the primary cause of disease or if it works best in combination with other drugs. Additional basic science research is required to address the fundamental role of senescent cells, especially in the established contexts of disease. Notes on Self-Experimentation with Sex Steroid Ablation for Regrowth of the Thymus https://www.fightaging.org/archives/2020/04/notes-on-se...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, our study demonstrated that Nrf2 deficiency promoted the increasing trend of autophagy during aging in skeletal muscle. Nrf2 deficiency and increasing age may cause excessive autophagy in skeletal muscle, which can be a potential mechanism for the development of sarcopenia. To What Degree is Chondrocyte Hypertrophy in Osteoarthritis Due to Cellular Senescence? https://www.fightaging.org/archives/2020/04/to-what-degree-is-chondrocyte-hypertrophy-in-osteoarthritis-due-to-cellular-senescence/ Senescent cells are large. They do not replicate, that function is disabled, but it is as if they go ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study delves into the mechanisms by which a short period of fasting can accelerate wound healing. Fasting triggers many of the same cellular stress responses, such as upregulated autophagy, as occur during the practice of calorie restriction. It isn't exactly the same, however, so it is always worth asking whether any specific biochemistry observed in either case does in fact occur in both situations. In particular, the period of refeeding following fasting appears to have beneficial effects that are distinct from those that occur while food is restricted. Multiple forms of therapeutic fasting have been repor...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study, for the first time, shows that transplantation of non-autologous mitochondria from healthy skeletal muscle cells into normal cardiomyocytes leads to short-term improvement of bioenergetics indicating "supercharged" state. However, over time these improved effects disappear, which suggests transplantation of mitochondria may have a potential application in settings where there is an acute stress. Outlining Some of the Science Behind Partial Reprogramming at Turn.bio https://www.fightaging.org/archives/2020/03/outlining-some-of-the-science-behind-partial-reprogramming-at-turn-bio/ Tur...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We report a new class of natural-product-inspired covalent inhibitors of telomerase that target the catalytic active site. Age-Related Epigenetic Changes that Suppress Mitochondrial Function https://www.fightaging.org/archives/2020/03/age-related-epigenetic-changes-that-suppress-mitochondrial-function/ Today's open access research reports on two specific epigenetic changes observed in old individuals that act to reduce mitochondrial function. This joins an existing list of genes for which expression changes are known to impact mitochondrial function with age. A herd of hundreds of mitochondria are found ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we intravenously administrated the young mitochondria into aged mice to evaluate whether energy production increase in aged tissues or age-related behaviors improved after the mitochondrial transplantation. The results showed that heterozygous mitochondrial DNA of both aged and young mouse coexisted in tissues of aged mice after mitochondrial administration, and meanwhile, ATP content in tissues increased while reactive oxygen species (ROS) level reduced. Besides, the mitotherapy significantly improved cognitive and motor performance of aged mice. Our study, at the first report in aged animals, not only prov...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, taller body height at the entry to adulthood, supposed to be a marker of early-life environment, is associated with lower risk of dementia diagnosis later in life. The association persisted when adjusted for educational level and intelligence test scores in young adulthood, suggesting that height is not just acting as an indicator of cognitive reserve. A Comparison of Biological Age Measurement Approaches https://www.fightaging.org/archives/2020/02/a-comparison-of-biological-age-measurement-approaches/ Researchers here assess the performance of a range of approaches to measuring biological...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
More News: Brain | Cancer | Cancer & Oncology | Diabetes | Endocrinology | Gastroschisis Repair | Geriatrics | Mitochondria | Mitochondrial Disease | Neurology