HKDC1 and TFEB in Maintenance of Mitophagy and Lysosomal Function
Researchers here report that HKDC1 is important in the autophagic processes that remove worn and damaged mitochondria, sending them to be recycled in the lysosome. Mitochondrial function declines with age, and this is thought to result in large part due to this decline in mitophagy, the name given to mitochondria-specific autophagy. Finding novel targets for therapies that might enhance mitophagy is a popular topic, despite the comparatively poor results obtained to date. Few of the existing approaches are better than exercise. Much more is needed if the objective is to significantly slow aging.
Mitochondria power...
Source: Fight Aging! - January 8, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Fight Aging! Newsletter, January 8th 2024
This study examined whether the local injection of the supernatant of activated PRP (saPRP) into the salivary gland (SG) could help prevent aging-induced SG dysfunction and explored the mechanisms responsible for the protective effects on the SG hypofunction.
Human salivary gland epithelial cells (hSGEC) were treated with saPRP or PRP after senescence through irradiation. The significant proliferation of hSGEC was observed in saPRP treated group compared to irradiation only group and irradiation + PRP group. Cellular senescence, apoptosis, and inflammation were significantly reduced in the saPRP group.
Th...
Source: Fight Aging! - January 7, 2024 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs
Standardization to a Single Epigenetic Clock is Much Overdue
In the past year or two, a great deal of effort on the part of leading researchers has gone into trying to standardize the use of a single epigenetic clock based on DNA methylation status of CpG sites on the genome. Suitable candidate universal mammalian clocks now exist. There are good reasons for standardization. Given that any large amount of omics data can be used to produce aging clocks, where "clock" in this context means a weighted combination of measured values that correlates well with chronological age or biological age, there is an essentially infinite number of potential clocks. People can build or cherry pick ...
Source: Fight Aging! - January 5, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Methionine Restriction Extends Life in Flies
A sizable fraction of the benefits to health and life span resulting from the practice of calorie restriction derive from regulatory systems that are triggered by nutrient sensing mechanisms focused on specific amino acids, primarily methionine. Thus a lowered dietary methionine intake produces health benefits even when overall calorie intake remains the same. This is well demonstrated in animal models, but not well tested in humans, despite the existence of low methionine medical diets. This may be because the medical diet are expensive, and it is neither straightforward nor easy to plan and eat a low methionine diet. Gui...
Source: Fight Aging! - January 5, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Platelet Rich Plasma Treatment Rescues Damaged Salivary Gland Function in Aged Mice
This study examined whether the local injection of the supernatant of activated PRP (saPRP) into the salivary gland (SG) could help prevent aging-induced SG dysfunction and explored the mechanisms responsible for the protective effects on the SG hypofunction.
Human salivary gland epithelial cells (hSGEC) were treated with saPRP or PRP after senescence through irradiation. The significant proliferation of hSGEC was observed in saPRP treated group compared to irradiation only group and irradiation + PRP group. Cellular senescence, apoptosis, and inflammation were significantly reduced in the saPRP group.
...
Source: Fight Aging! - January 5, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Sirtuin 2 Overexpression Fails to Extend Life in Mice
One long-lasting result of the hype engineered over sirtuin 1 overexpression as a possible avenue to modestly slow aging is a continued focus on other sirtuins in the context of aging. Sirtuin 1 overexpression turned out to be entirely unimpressive, a dead end. Sirtuin 6, however, is more interesting, and overexpression in mice does modestly extend life span, possibly by improving DNA repair efficiency. It may also be the case that sirtuin 3 overexpression can improve mitochondrial function to a great enough degree to also be interesting.
On the whole, however, this sort of approach to manipulating metabolism has y...
Source: Fight Aging! - January 4, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Cellular Senescence in the Aging and Dysfunction of Skin
A great deal of research and development effort is now focused on finding ways to reduce the contribution of senescent cells to degenerative aging. Initiatives range from fundamental research into the biochemistry of senescent cells to clinical trials of early senolytic therapies capable of selectively destroying senescent cells. A growing burden of senescent cells is a feature of all organs and tissues in the body, the skin included. Researchers here discuss what is known of the role of cellular senescence in aging and dysfunction of skin, and what might be done about it.
The skin is the largest organ of the huma...
Source: Fight Aging! - January 4, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Apolipoprotein E is a Longevity-Associated Gene
It remains unclear as to why apolipoprotein E (APOE) variants are associated with longevity in humans. The gene has a well-studied role in Alzheimer's disease, but the reasons why APOE variants are associated with aging remain to be determined. The most likely mechanisms involve (a) interactions with age-related disruptions of lipid metabolism, both in the brain and elsewhere, and (b) indirect effects on the inflammatory behavior of innate immune cells such as microglia. There are plenty of other interactions to further study, however, such as in bone tissue, or effects on the gut microbiome. As is often the case, a great ...
Source: Fight Aging! - January 4, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Is Alternative Splicing a Meaningful Cause of Degenerative Aging, or Largely a Downstream Side-Effect?
A gene sequence consists of a mix of shorter sequences, only some of which are used to manufacture the protein encoded in that gene. Exon sequences are included and intron sequences are excluded. Nothing is ever quite that simple, of course, but changes in which exons and introns end up in a protein enable multiple proteins to be produced from a single gene sequence. Sometimes this is an accident, assome genes are prone to accidental production of truncated or extended proteins that are toxic. Sometimes this is an evolutionary reuse in which a gene produces several different vital proteins with quite different functions.
...
Source: Fight Aging! - January 3, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Inflammatory Microglia in Degenerative Aging and Alzheimer's Disease
Microglia, the innate immune cells of the central nervous system, can enter an aggressive, inflammatory state in response to the presence of molecular waste, inflammatory signaling, mitochondrial damage, and so forth. They can also become senescent, which is also a pro-inflammatory state. The aging brain, and particularly the brains of patients with neurodegenerative conditions, exhibit a state of chronic inflammation, producing dysfunction, cell stress, and cell death. It remains to be seen as to how effective anti-inflammatory therapies targeting microglia will be in the treatment of neurodegenerative conditions and the ...
Source: Fight Aging! - January 3, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Calorie Restriction Mimetics as an Approach to Slow Demyelination
Myelin sheathes axons, the connections between neurons. This sheath is essential to nervous system function, and a range of unpleasant diseases result from loss of myelin, such as through the autoimmune activity of multiple sclerosis. Demyelination occurs to a lesser degree over the course of aging, the standard problem of a complex system becoming disarrayed as the result of various forms of molecular damage and maladaptive reactions to that damage. Here, as elsewhere, chronic inflammation appears to be a contributing cause. Calorie restriction is known to dampen chronic inflammation and favorably alter the behavior of ce...
Source: Fight Aging! - January 3, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Failing Mitochondrial Quality Control in Aging and Neurodegeneration
Every one of our cells contains hundreds of mitochondria, the descendants of ancient symbiotic bacteria now fully integrated into our biochemistry. Mitochondria contain their own small remnant genome, the mitochondrial DNA, replicate like bacteria, and toil to produce adenosine triphosphate (ATP), a chemical energy store molecule used to power cell processes. Mitochondrial function declines with age, unfortunately, and our cells suffer for it. This contributes meaningfully to many age-related conditions. This decline appears to result in large part from changes in gene expression that impair the various quality control pro...
Source: Fight Aging! - January 2, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
A Look at the Signaling that Produces Bystander Senescence
The burden of senescent cells in tissues throughout the body increases with age, as the immune system becomes ever less capable of clearing such cells in a timely fashion. Senescent cells do not replicate, but instead devote their energies to the production of pro-growth, pro-inflammatory signaling that is disruptive to tissue structure and function when maintained for the long term. These cells actively contribute to degenerative aging in this way. Senescent cells are not just produced by reaching the Hayflick limit, or by damage of some sort. They can also become senescent in response to the signaling of other senescent ...
Source: Fight Aging! - January 2, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Aptamers to Reduce Inflammatory AGE-RAGE Interaction
Researchers here discuss the use of aptamers that can bind to advanced glycation endproducts (AGEs). This prevents the AGEs from themselves binding to the receptor for AGEs (RAGE), an interaction that provokes inflammation. A sizable presence of circulating, short-lived AGEs is characteristic of the abnormal metabolism of obesity and obesity-related conditions such as type 2 diabetes. It is an open question as to how much of a contribution to the chronic inflammation of aging is provided by AGEs in people of a normal weight, eating a basically sensible diet, however. The only way to find out is to test a therapy of this na...
Source: Fight Aging! - January 2, 2024 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Should We Think of Rheumatoid Arthritis as an Age-Related Condition?
There are medical conditions that occur only in old age, and there are medical conditions, such as cancer, that can occur at any point in life, but more so in the old. Then there are grey area conditions that may occur to some greater degree in later life, or be worse in later life, but this is by no means widely appreciated. Where does the autoimmune condition of rheumatoid arthritis sit in this spectrum? Unlike cancer, it is not commonly thought of as an age-related disease, even though it is certainly affected and made worse by the processes of aging. This point is discussed in today's open access commentary and the pap...
Source: Fight Aging! - January 1, 2024 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
