Details on the LEV Foundation's First Study of Combined Interventions in Mice
The recently launched Longevity Escape Velocity (LEV) Foundation will, initially at least, focus on testing combinations of interventions. This work is informed by the SENS view of aging, in that degenerative aging is produced by a limited number of forms of cell and tissue damage that result from the normal operation of metabolism. These include the accumulation of senescent cells, cross-linking of the extracellular matrix, mitochondrial DNA damage, and so forth. Each form of damage produces its own contribution to a complex web of interacting downstream consequences, so while repairing any one form of damage should be be...
Source: Fight Aging! - December 19, 2022 Category: Research Authors: Reason Tags: Activism, Advocacy and Education Source Type: blogs
Fight Aging! Newsletter, December 19th 2022
In conclusion, p16 deletion or p16 positive cell clearance could be a novel strategy preventing long term HFD-induced skin aging.
Association of LDL-Cholesterol with Mortality
https://www.fightaging.org/archives/2022/12/association-of-ldl-cholesterol-with-mortality/
Researchers here report on a study of LDL-cholesterol and mortality risk in older people. As they note, data on this topic is conflicted once one moves beyond the matter of cardiovascular disease. Over a lifetime, higher LDL-cholesterol makes it easier to reach the tipping point at which cholesterol deposited in blood vessel walls produces e...
Source: Fight Aging! - December 18, 2022 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs
Neutrophils Play a Role in the Age-Related Decline of Hematopoietic Function
Hematopoietic stem cells and progenitor cells in the bone marrow produce the red blood cells and immune cells needed for the body to function. Changes in this hematopoietic system make up one the major factors in the age-related decline of the immune system into the incapacity of immunosenescence and chronic inflammatory state known as inflammaging. There is a decline in the diversity of cell populations tasked with producing immune cells, and the types of immune cell produced shifts to favor myeloid lineages of the innate immune system over lymphoid lineages of the adaptive immune system.
The age-related decline of...
Source: Fight Aging! - December 16, 2022 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Chronic Chromatin Activation in Aged Muscle Stem Cells
In this study, we examined the chromatin accessibility changes of SCs, from quiescence exit, early activation, and regeneration, showing the trajectory of chromatin environment changes for SC activation in young and aged conditions. We showed that the chromatin environment of SCs is very compact during quiescence, becomes highly accessible on early activation, and gradually re-establish the compact state after long-term regeneration. We found that the old SCs exhibit a much more open chromatin environment, suggesting that the old SCs exhibit a chronically activated chromatin state.
Link: https://doi.org/10.1016/j....
Source: Fight Aging! - December 16, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Reviewing the Role of SIRT6 in Aging
While much the history of work on sirtuins is one of disappointing results, the majority of that work involved SIRT1. Both SIRT3 and SIRT6 may be more interesting, based on animal studies conducted since the SIRT1 era. SIRT3 localizes to the mitochondria, and mitochondrial function is important in the context of aging. Researchers have shown that SIRT3 upregulation in mice improves hematopoietic stem cell function. SIRT6 upregulation, however, has been shown to modestly extend life in mice, there is a larger body of work surrounding its effects on metabolism than is the case for SIRT3, and at least one group is attempting ...
Source: Fight Aging! - December 12, 2022 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Fight Aging! Newsletter, December 12th 2022
In conclusion, selective removal of senescent dermal fibroblasts can improve the skin aging phenotype, indicating that BPTES may be an effective novel therapeutic agent for skin aging.
Non-Dividing Neurons Do In Fact Become Senescent, Impairing Brain Function
https://www.fightaging.org/archives/2022/12/non-dividing-neurons-do-in-fact-become-senescent-impairing-brain-function/
Cellular senescence is generally thought of as a characteristic of replicating cells; it is an end state reached when telomeres, reduced in length with each cell division, become too short. This is followed by programmed cell death...
Source: Fight Aging! - December 11, 2022 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs
A Long Discussion of the Role of Senescent Cells in Idiopathic Pulmonary Fibrosis
Senescent cells are constantly created and destroyed throughout life, largely as a result of the replicative senescence that marks the end of life for a somatic cell, the Hayflick limit on cell division. With age, the pace of creation and destruction is disrupted, perhaps largely because the immune system ages to the point at which it falters in all of its tasks, clearance of senescent cells included. Senescent cells accumulate, and while never making up more than a small fraction of all somatic cells in any given tissue, the pro-growth, pro-inflammatory signaling generated by senescent cells is highly disruptive to organ ...
Source: Fight Aging! - December 9, 2022 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Assessing Mitochondrial Transfer Into Senescent Cells In Vitro
Researchers here report on in vitro experiments to show that introducing functional mitochondria into a cell culture containing senescent cells reduces markers of senescence. It is an interesting question as to how this would work in living tissue, where the numbers of senescent cells are low, and mitochondria will be introduced into all cells. Since several companies are developing mitochondrial transfer as a therapy to treat the loss of mitochondrial function that is characteristic of age-related disease, we'll find out in the years ahead. Those groups are not specifically targeting cellular senescence, but can hardly av...
Source: Fight Aging! - December 8, 2022 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Thymic Macrophage Populations Change with Age
The thymus atrophies with age, limiting the supply of new T cells to support the adaptive immune system. This is an important aspect of immune aging. Digging deeper into the mechanisms of thymus aging is of interest to the extent that it might reveal practical approaches to intervention. The challenge of the thymus is near entirely its inaccessible location, making it hard to deliver the known factors that can induce thymic regrowth without side-effects in the rest of the body. Here, researchers find that one population of macrophages characteristic of thymic tissue diminishes with age, while another population expands. Th...
Source: Fight Aging! - December 8, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Investigating the Role of Microglia in Zebrafish Neural Regeneration
In this study, we used a stab wound injury model in zebrafish and identified an injury-induced microglial state characterized by the accumulation of lipid droplets and TDP-43+ condensates. Granulin-mediated clearance of both lipid droplets and TDP-43+ condensates was necessary and sufficient to promote the return of microglia back to the basal state and achieve scarless regeneration.
Moreover, in postmortem cortical brain tissues from patients with traumatic brain injury, the extent of microglial activation correlated with the accumulation of lipid droplets and TDP-43+ condensates. Together, our results reveal a mec...
Source: Fight Aging! - December 6, 2022 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Cellular Enlargement in Aging, a Poorly Studied Topic
Some cells are small, others large. Cell size is connected to cell function, and different varieties of cell maintain tight control over their various different sizes. Senescent cells are known to become much larger than their origin cell type, and one effort to detect senescent cells in blood samples made use of this feature. Do non-senescent cells lose control of size in old tissues, however? To what degree is this a feature of aging that produces further downstream issues, versus being a consequence of other problematic changes in cell behavior that occur with age? These are not well-studied questions.
A large ...
Source: Fight Aging! - December 5, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Fight Aging! Newsletter, December 5th 2022
In conclusion, the PAAIs examined (i.e. mTOR loss of function, Ghrhr loss of function, intermittent fasting-based version of dietary restriction) often influenced age-sensitive traits in a direct way and not by slowing age-dependent change. Previous studies often failed to include young animals subjected to PAAI to account for age-independent PAAI effects. However, any study not accounting for such age-independent intervention effects will be prone to overestimate the extent to which an intervention delays the effects of aging on the phenotypes studied. This can result in a considerable bias of our view on how modifiable a...
Source: Fight Aging! - December 4, 2022 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs
To What Degree Can Cell Therapies Rebuild the Aging Brain?
Repair of the aging brain is perhaps the most important of goals in regenerative medicine. We are the data that is stored in some way within the small-scale structures of our brain tissue, and so the options for outright replacement of brain cells and tissues are somewhat constrained. As a thought experiment, it is in principle possible, given significant progress in biotechnology, to manufacture a cloned body to receive a transplanted brain. All of the steps needed either already happen in nature, such as the growth of bodies without brains, and would need control and direction, or have been crudely demonstrated in animal...
Source: Fight Aging! - November 29, 2022 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs
Reviewing the State of Gene Editing to Make Cells Compatible Between Donor and Recipient
A sizable level of funding in academia and industry is devoted to the goal of enabling cell transplants between different individuals, with large and well funded pharma companies such as Astellas, Sana, and others involved. This would allow for the creation of cost-effective cell therapies of all sorts, in which the donor cells used in every patient originate from the same few well-vetted and well-controlled cell lines.
Logistics is everything in the realm of cell therapies, and the reason why autologous cell therapies, such as CAR-T treatments for cancer, are so expensive is that every treatment site must have the ...
Source: Fight Aging! - November 29, 2022 Category: Research Authors: Reason Tags: Daily News Source Type: blogs
Fight Aging! Newsletter, November 28th 2022
This study explored whether determining the gain or loss of specific taxa represent a more precise metric of healthy/unhealthy aging than summary microbiome statistics, such as diversity and uniqueness. We analyzed microbiome diversity and four measures of microbiome uniqueness in 21,000 gut microbiomes for their relationship with aging and health. We show that diversity and uniqueness measures are not synonymous; uniqueness is not a uniformly desirable feature of the aging microbiome, nor is it an accurate biomarker of healthy aging. Different measures of uniqueness show different associations with diversity and with mark...
Source: Fight Aging! - November 27, 2022 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs
