![]() ![]() Increasing our knowledge of the effects that vascular changes can have on cognition would be especially relevant for clinicians working in cognitive assessment with MCI and AD patients. However, comparing the differences of the effects on cognitive functions between the groups has not typically been the main focus. have described WM lesions as affecting cognition both directly and indirectly through grey matter thickness, similarly for both cognitively healthy and cognitively impaired (MCI/AD). For example increased WM lesion load has been found to correlate with cognitive impairment in patients with AD, and shown to predict the rate of cognitive decline in AD. Some studies have examined the effects of vascular brain changes on cognitive function in mild cognitive impairment (MCI) and AD. Additionally, cerebrovascular risk factors such as hypertension, smoking, and diabetes are also risk factors for AD. Furthermore, comorbid vascular brain changes are often present in patients with Alzheimer’s disease (AD), with a number of WM pathways having been implicated as manifesting significant degeneration in AD. The functional consequences of these brain changes are related to their severity and extent, and can range from almost none via mild cognitive decline to dementia. The researchers conclude: “Our results clearly show a novel function of DAO as a promoter of DNA damage-induced senescence, which may provide new insights into the roles of -amino acids in various physiological and pathological processes including senescence, cancer, and aging.Aging is often associated with vascular white matter (WM) brain pathology. In this respect, the study identifies a previously unknown role for DAO. Perhaps it is the overproduction of ROS that causes problems and tips the balance toward cell stress, disease, and aging. For example, low levels of ROS can lengthen the lifespan, and the immune system needs them to fight infection. ROS are not always the bad guys: They can also benefit health. The researchers are cautious about the implications of their findings. In further experiments, the scientists discovered other pathways that help DAO to promote senescence triggered by DNA damage.Ī key factor is the transporter gene SLC52A1, which helps increase levels of the coenzyme flavin adenine dinucleotide (FAD).ĭAO needs a supply of FAD, and SLC52A1 ensures this supply by increasing the availability of vitamin B-2, an ingredient of FAD. The team suggests that this proves that it is DAO’s ability as an enzyme to make ROS that allows it to promote senescence in cells. This version of DAO, however, neither produced ROS nor promoted senescence. In another experiment, they used a mutant of DAO that stopped it behaving like an enzyme. They found, however, that reducing DAO activity, either with drugs or by silencing its gene, reduced senescence and ROS production. In their more recent investigation, the researchers coaxed cancer cells into senescence by exposing them to low levels of “an anticancer drug that induces DNA double-strand breaks.” However, that “study did not fully explore the direct relationship between DAO and senescence,” they note. In previous work, the Kobe University researchers had discovered that senescence triggers the tumor suppressor molecule p53 and that this activates the gene for DAO. ![]() In addition, there is a growing body of knowledge about how aging-related biological changes and diseases involve ROS and senescence. Since then, however, studies have revealed that senescent cells are active in tissue repair, wound healing, embryonic development, and aging.Ī major focus of continuing research is on the various stressors that can trigger cells to enter the irreversible state. Confined to a senescent state, cells with damaged DNA cannot multiply and give rise to tumors. The recent study adds to a growing understanding of the role of senescent cells in this relationship.Įntering an irreversible state in which it can no longer divide and proliferate does not necessarily diminish a cell’s capacity for change and influence.Įarly research suggested that the main impact of cell senescence on human biology involved protecting against cancer. ROS are important players in the biology of aging and many diseases that tend to increase with advancing age, such as Parkinson’s, Alzheimer’s, diabetes, and many cancers.
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