eIF2 α as a Target to Prevent T Cell Stress and Loss of Function in Cancer Immunotherapy
Researchers here identify eIF2α as a target for interventions that prevent T cells from shutting down after prolonged activity in a tumor environment. The stress response to extended activity is normally protective, but in this case it prevents T cells from being as effective as they might be, which contributes to an established tumor's compromise of the immune system. This sort of approach offers the promise of improving cancer immunotherapies, increasing the damage that each T cell can do to tumor tissue. The stress response in T cells can lead to their inability to curtail tumor growth. Researchers found that ...
Source: Fight Aging! - December 27, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

MERTK Inhibition Increases Bone Density via Increased Osteoblast Activity
Bone density results from the balance of constant activity on the part of osteoblasts and osteoclasts, the former building bone, the latter breaking it down. With advancing age, the balance of activity shifts to favor osteoclasts, producing a gradual loss of bone density that leads to osteoporosis. Therapies have to date typically attempted to reduce osteoclast activity, but researchers here note an approach based on increased osteoblast activity. Bones appear to be durable and solid. But appearances are deceptive: in fact, bone tissue is in a constant state of remodeling. Bone-degrading osteoclasts and bone-build...
Source: Fight Aging! - December 27, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Probiotics versus Neuroinflammation and Its Consequences
The balance of microbial populations making up the gut microbiome is now known to change with age in ways that promote chronic inflammation. There are more inflammatory microbes passing the intestinal barrier to enter tissue, and more microbes capable of generating harmful metabolites that aggravate cells. The aging of the microbiome is only loosely connected to the aging of the body, however. Animal studies make it clear that the gut microbiome of an old individual can be restored to a youthful balance of populations via fecal microbiota transplant from a young individual, benefits to health and longevity result, and that...
Source: Fight Aging! - December 26, 2022 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Monocytes Become More Inflammatory with Age
In conclusion, circulating monocytes in older adults exhibit increased expression of activation, adhesion, and migration markers, but decreased expression of co-inhibitory molecules. Link: https://doi.org/10.1186/s12979-022-00321-9 (Source: Fight Aging!)
Source: Fight Aging! - December 26, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Progress Towards Decoupling Epigenetic Rejuvenation from Cell Identity Change in Partial Reprogramming
Reprogramming cells using the Yamanaka factors produces both a reset of epigenetic patterns to a more youthful configuration and a change in cell identify. One of the primary challenges inherent in reprogramming to achieve rejuvenation is avoidance of this altered cell identity. Reprogramming isn't an immediate switch, it is a slow process over hours to days, but a fraction of reprogrammed cells do change into induced pluripotent stem cells after some period of exposure to reprogramming factors. This is an undesirable outcome when delivering a reprogramming therapy; if new approaches can be found that do not alter cell ide...
Source: Fight Aging! - December 26, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fight Aging! Newsletter, December 26th 2022
This article on senolytic therapies to selectively remove senescent cells in old tissues is in part a matter of Unity Biotechnology talking up their position. The company suffered from first mover disadvantage in bringing senolytic drugs into clinical development. The field has made progress very rapidly over the last decade, and startups founded even just a couple of years after Unity's launch benefited from greater knowledge and a selection of better technologies to work with. Still, one can be talking up one's position and also be right. The accumulation of senescent cells is profoundly harmful, a significant contributi...
Source: Fight Aging! - December 25, 2022 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Longer RNA Transcripts Exhibit Greater Alterations in Amount with Aging
We present three lines of evidence supporting the biological importance of the uncovered transcriptome imbalance. First, in vertebrates the length association primarily displays a lower relative abundance of long transcripts in aging. Second, eight antiaging interventions of the Interventions Testing Program of the National Institute on Aging can counter this length association. Third, we find that in humans and mice the genes with the longest transcripts enrich for genes reported to extend lifespan, whereas those with the shortest transcripts enrich for genes reported to shorten lifespan. Perhaps the most pressing ...
Source: Fight Aging! - December 23, 2022 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

On the Aging of the Kidneys
The longevity-associated gene klotho is known to act in kidney tissue, in ways that are protective of cell function in the aging environment of damage and inflammation. One of the conclusions that might be drawn from the extended life span produced by increased klotho expression in animal studies is that declining kidney function is an important aspect of aging. If the kidneys are not efficiently clearing waste from the bloodstream, and otherwise providing their contribution to bodily function, then all organs suffer as a result. Faster loss of kidney function means a faster decline into disease and mortality. The...
Source: Fight Aging! - December 23, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

A Role for Raised Ceramide Levels in Sarcopenia
Researchers here provide evidence for raised levels of ceramide in muscle tissue to be an important part of the metabolic dysfunction of aging. It reduces muscle stem cell activity, contributing to the age-related loss of muscle mass and strength that leads to sarcopenia and frailty. Whether working on this point of intervention, to produce improved ceramide blockers with fewer side-effects, is better or worse than other avenues is an open question. Altered metabolism is thought to be a fair way downstream from the root causes of aging, and tackling root causes should always be a better option. It is is very challenging to...
Source: Fight Aging! - December 23, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

A Cautious Industry View of the Promise of Senolytics
This article on senolytic therapies to selectively remove senescent cells in old tissues is in part a matter of Unity Biotechnology talking up their position. The company suffered from first mover disadvantage in bringing senolytic drugs into clinical development. The field has made progress very rapidly over the last decade, and startups founded even just a couple of years after Unity's launch benefited from greater knowledge and a selection of better technologies to work with. Still, one can be talking up one's position and also be right. The accumulation of senescent cells is profoundly harmful, a significant contributi...
Source: Fight Aging! - December 22, 2022 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

A Study in Which Exercise Fails to Improve Cognitive Function
It is interesting to see a study in which exercise failed to improve memory function in older adults, given the sizable number of studies showing that it does help. One possibility is that intensity of exercise matters. In general, however, the literature leans in the direction of exercise slowing cognitive decline. Yet no outcome in research is so guaranteed that there will be a complete absence of studies in which it fails to show up in the data; this is one of the challenges inherent in following the output of the scientific community. A large study that focused on whether exercise and mindfulness training coul...
Source: Fight Aging! - December 22, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Correlations Between Gut Microbiome Composition and Longevity
A great deal of research is focused on cataloguing and correlating specific differences in the gut microbiome with aspects of aging. In years ahead, techniques will be developed to more precisely control the composition of the gut microbiome, removing issues such as too great a number of inflammatory microbes, or those producing harmful metabolites. At the moment, only more crude approaches such as fecal microbiota transplantation from a young donor are well developed. In principle it should be possible to take a probiotic approach and use oral administration to achieve a similar outcome, a rejuvenated gut microbiome, but ...
Source: Fight Aging! - December 22, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

In Search of Early Biomarkers of LATE, a Form of Dementia Related to TDP-43 Aggregation
LATE is a comparatively recently discovered form of dementia, connected to aggregation of misfolded TDP-43, one of the few proteins in the body capable of taking on an altered form that encourages other molecules of the same protein to also adopt that form and join together to form clumps. Aggregates are disruptive of cell function, but it is a slow process to understand exactly why this is the case. Researchers have been working on understanding amyloid-β aggregates for decades now, and continue to find that the present state of knowledge is incomplete regarding how the toxic halo of biochemistry that surrounds aggregate...
Source: Fight Aging! - December 21, 2022 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Inflammatory T Cells Found in Cerebrospinal Fluid of Cognitive Impairment Patients
Inflammation in brain tissue is a feature of neurodegenerative conditions, and chronic inflammation is a feature of aging in general. This unresolved inflammatory signaling is disruptive to normal tissue structure and function. Researchers here note a consequence of inflammation in the innate immune cells of the brain, microglia. They produce a signal that draws in active, inflammatory T cells from the body in large numbers, which no doubt makes the situation worse. Normally there is little traffic between the separate immune systems of the brain and body, but the blood-brain barrier enforcing that separation becomes leaky...
Source: Fight Aging! - December 21, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Enhancer DNA Sequence from Zebrafish Can Induce Targeted Heart Regeneration in Mice
This very interesting work involves identifying enhancer DNA sequences that regulate regeneration in an exceptionally regenerative species, such as zebrafish, and introducing these sequences into mammals via gene therapy. The researchers find a sequence that can be used to regulate expression of genes that drive heart regeneration following injury, a desirable goal given that mammalian hearts regenerate poorly. Zebrafish are capable of scarless healing of heart injuries, and connecting the zebrafish enhancer to mammalian growth genes can improve regeneration, by expressing these genes at the appropriate time in the context...
Source: Fight Aging! - December 21, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs