Read More at Fight Aging! Researchers here report on an interesting in vitro demonstration, in which they show that hydrogen peroxide (H2O2) generated in mitochondria does not cause nuclear DNA damage. Oxidizing molecules generated as a byproduct of mitochondrial generation of the chemical energy store molecule adenosine triphosphate (ATP) are thought to be important in aging. Oxidative stress is a feature of aging and age-related changes to mitochondrial structure, dynamics, and function. Oxidative damage to nuclear DNA is also a feature of this cell-wide oxidative stress, and it is commonly thought that mitochondria are the source of this stress and thus this damage. But perhaps they are not. Reactive Oxygen Species (ROS) derived from mitochondrial respiration are frequently cited as a major source of chromosomal DNA mutations that contribute to cancer development and aging. However, experimental evidence showing that ROS…
A Skeptical View of the Role of Nuclear DNA Damage in Aging
Read More at Fight Aging! It is evident and settled that stochastic nuclear DNA damage contributes to cancer. The more of it that you have, the worse your risk. What is still very much debated is whether nuclear DNA damage contributes meaningfully to degenerative aging, and how it does so. Most mutational damage to DNA occurs in regions that are inactive, in cells that have comparatively few divisions remaining before reaching the Hayflick limit. Even if damage alters the function of such a cell, in some non-cancerous way, it is unclear as to how this could amount to a meaningful contribution to loss of tissue function. The one school of thought is focused on somatic mosaicism, the spread of mutations throughout a tissue when mutational damage occurs in stem cells. In this case subtle dysfunctions could accumulate and interact with…
DNA Damage and Inflammation in Aging
Read More at Fight Aging! Both stochastic DNA damage and chronic inflammation are characteristic of aging. DNA damage can contribute to inflammatory signaling via a range of mechanisms, but, as noted here, it is challenging in a system as complex as our cellular biochemistry to pick apart the relative importance of these mechanisms. It is nonetheless reasonable to think that some fraction of the unresolved inflammation of aging, disruptive to tissue function throughout the body, results from the increased amount of DNA damage in later life. Persistent DNA lesions build up with aging triggering inflammation, the body’s first line of immune defense strategy against foreign pathogens and irritants. Once established, DNA damage-driven inflammation takes on a momentum of its own, due to the amplification and feedback loops of the immune system leading to cellular malfunction, tissue degenerative changes, and metabolic…
Connections Between Epigenetic Aging and Nuclear DNA Damage
Read More at Fight Aging! Today’s open access paper reviews what is known of the connections between epigenetic aging and the nuclear DNA damage that occurs across a lifetime, and particularly in later life. Some of this DNA damage is more evidently connected with the epigenetic regulation that determines the packaging and structure of nuclear DNA, such as the activity of transposable elements, restrained in youth, but unleashed to copy themselves in later life, damaging genes as they do so. It is important to note that the relationship of cause and consequence between nuclear DNA damage and epigenetic change is likely a two-way street, particularly given the comparatively recent discovery that repeated double strand break repair causes epigenetic alterations characteristic of aging. While nuclear DNA damage raises the risk of cancer, such as via damage to cancer suppression genes, it…