Fight Aging! Newsletter, January 30th 2023
In conclusion, deletion of p16Ink4a cells did not negatively impact beta-cell mass and blood glucose under basal and HFD conditions and proliferation was restored in a subset of HFD mice opening further therapeutic targets in the treatment of diabetes. Communication Between Blood and Brain in Aging and Rejuvenation https://www.fightaging.org/archives/2023/01/communication-between-blood-and-brain-in-aging-and-rejuvenation/ As noted here, joining the circulatory systems of an old and young mouse results in some degree of rejuvenation in the old mouse. Where brain function is improved, researchers are inte...
Source: Fight Aging! - January 29, 2023 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Towards Microneedle Delivery of LNP-mRNA Gene Therapies for Skin Aging
The skin is arguably one of the easiest of the large organs in the body to target for delivery of gene therapies, via established microneedle approaches. Nonetheless, much of the initial thrust of gene therapy clinical development focused instead on the liver, one of the other more tractable targets. Most material injected into the bloodstream ends up in the liver, and a single injection is logistically easier than coverage of large amounts of skin via microneedle patches, among other reasons. Given the advent of messenger RNA (mRNA) encapsulated in lipid nanoparticles (either artificial or repurposed extracellular ...
Source: Fight Aging! - January 27, 2023 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Reversine Increases Cell Plasticity, and Appears to Allow Some Cell Types to Escape Senescence
If I'm understanding the results presented here correctly, the reversine small molecule enables senescent cells to return to a more normal state of function, including replication, at least in muscle cells examined in cell culture. The researchers believe it is triggering some of the same reprogramming pathways as the Yamanaka factors, perhaps by inducing expression of Oct4, but are not yet certain as to what is going on under the hood. Is it a good idea to take senescent cells in the body and return them to normal function? That is a good question, and has been raised for other approaches to senescence reversal. At least ...
Source: Fight Aging! - January 27, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Osteopontin Plays Diverse Roles in Degenerative Aging
Osteopontin levels are higher in blood samples taken from older people than in those taken from young people. It is a component of the senescence-associated secretory phenotype (SASP) produced by senescent cells, disruptive to tissue function. Osteopontin acts as a regulator in a number of tissues, and appears to be relevant to the age-related decline, such as of hematopoiesis and muscle function. Here, researchers review what is known of the role of osteopontin in aging. Osteopontin (OPN) is a multifunctional noncollagenous matrix phosphoprotein that is expressed both intracellularly and extracellularly in variou...
Source: Fight Aging! - January 27, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Investigating the Comparative Biology of Variations in Rockfish Species Life Spans
The comparative biology of aging, the study of aging in species with widely divergent life spans, is hoped to improve the catalog and understanding of important mechanisms of aging. It may or may not turn out to be the case that the biochemistry of long-lived species can give rise to practical therapies that slow aspects of human aging, at least in the near future of the next few decades. Engineering a human that ages more slowly seems a far more daunting task than the production of rejuvenation therapies that repair the known forms of cell and tissue damage that drive aging. An alternative to comparing other specie...
Source: Fight Aging! - January 26, 2023 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Communication Between Blood and Brain in Aging and Rejuvenation
As noted here, joining the circulatory systems of an old and young mouse results in some degree of rejuvenation in the old mouse. Where brain function is improved, researchers are interested in how changes in the blood signaling environment might be involved. While research initially focused on factors in young blood that are reduced in old blood, it is increasingly thought that the important mechanism is a dilution of harmful factors carried in the old bloodstream. This has led to a few studies of plasma transfer and dilution in humans, and at least one company attempting to determine the optimal dose and protocol to make...
Source: Fight Aging! - January 26, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Clearing Senescent Cells as a Treatment for Type 2 Diabetes
In conclusion, deletion of p16Ink4a cells did not negatively impact beta-cell mass and blood glucose under basal and HFD conditions and proliferation was restored in a subset of HFD mice opening further therapeutic targets in the treatment of diabetes. Link: https://doi.org/10.18632/aging.204483 (Source: Fight Aging!)
Source: Fight Aging! - January 26, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Considering Autophagy in Long-Lived Species
To what degree is autophagy important in the sizable differences in life span between mammalian species? That is an interesting question. It appears that long-lived species exhibit more effective autophagy, and it also appears that many of the methods of altering metabolism in order to modestly slow aging that were discovered over the past thirty years involve upregulation of autophagy. The effects of calorie restriction on longevity depend upon the correct function of autophagy, and vanish if autophagy is disabled. It is worth noting that autophagy is difficult to measure, however. It involves many distinct process...
Source: Fight Aging! - January 25, 2023 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Senescent Cells Degrade Intestinal Stem Cell Function
Senescent cells are constantly created and destroyed in all tissues of the body throughout life, but the number present at any given time increases with age, in large part because the immune system ceases to clear senescent cells as efficiently as it should. Senescent cells secrete pro-growth, pro-inflammatory factors that are useful in the short term, such as during wound healing, or to draw attention to potentially cancerous cells. When kept up for the long term, however, the signaling of senescent cells is highly disruptive to tissue structure and function. The example given here, of disrupted intestinal stem cell funct...
Source: Fight Aging! - January 25, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Mitochondrial Dynamics Triggers Inflammation When Too Imbalanced in Either Direction
In this study, we provide evidence that mitochondrial dynamics also controls the activation of intracellular inflammatory pathways. Our conclusion is based on a number of observations, namely that: a) repression of the mitochondrial fusion proteins Mfn1 or Mfn2 induces mitochondrial fragmentation and TLR9-dependent NFκB activation; and b) Drp1 or Fis1 repression causes mitochondrial elongation and both NFκB-dependent and type I IFN inflammatory responses. Given the role of mitochondrial dynamics in regulating mitochondrial function and mitophagy, it is conceivable that alterations in these processes could be invo...
Source: Fight Aging! - January 25, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Senotherapeutics Will Reduce the Side-Effects of Cancer Radiotherapy
Treatment with radiation to kill cancerous cells results in an increased burden of senescent cells, both in and around the tumor. This is a fair trade-off; a senescent cancerous cell may be harmful in and of itself, but it is a good deal less harmful in the long run than an active cancer cell. Unfortunately senescent cells produce pro-growth, pro-inflammatory signaling that is disruptive of tissue function, raises the risk of suffering a range of age-related conditions, and increases the risk of both reoccurrence of the treated cancer and the development of later unrelated cancers. Thus given the work taking place o...
Source: Fight Aging! - January 24, 2023 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

The Unambitious Approaches to Improving the Gut Microbiome
For every researcher interested in new approaches, there are another few whose horizons end at supplements and exercise. Thus one finds papers like this one, in which the authors discuss whether probiotics and exercise can help to ameliorate the aging of the gut microbiome. It seems a little ridiculous to focus completely on these options in a world in which fecal microbiota transplantation has been shown to produce much larger, lasting effects on the gut microbiome following a single treatment, and a few other less well developed options on the table, such as flagellin immunization, may prove to be as effective and useful...
Source: Fight Aging! - January 24, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Discussing the Hallmarks of Aging in the Context of Alzheimer's Disease
This article will focus on the primary aging hallmarks as these are interconnected with other aging characteristics and are at the base of the hierarchical order of aging features, and have been shown to be related to AD. It is an attempt to improve our understanding of the pathological mechanisms of AD to find potential therapeutic approaches and diagnostic tools. Link: https://doi.org/10.7150/thno.79535 (Source: Fight Aging!)
Source: Fight Aging! - January 24, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs

Fecal Microbiota Transplant From Young to Old Mice Reduces Inflammation and Improves Hematopoiesis
In this study, we performed fecal microbiota transplantation (FMT) from young mice to aged mice and observed significant increment in lymphoid differentiation and decrease in myeloid differentiation in aged recipient mice. Further, FMT from young mice rejuvenated aged HSCs with enhanced short-term and long-term hematopoietic repopulation capacity. Mechanistically, single-cell RNA sequencing deciphered that FMT from young mice mitigated inflammatory signals, upregulated FoxO signaling pathway and promoted lymphoid differentiation of HSCs during aging. Finally, integrated microbiome and metabolome analyses uncovered that FMT...
Source: Fight Aging! - January 23, 2023 Category: Research Authors: Reason Tags: Medicine, Biotech, Research Source Type: blogs

Cyclarity's Approach to Treating Atherosclerosis
The treatment of atherosclerosis is trapped in a rut, and has been for some time. Near all of the development in this field is focused on producing ever more innovative ways to reduce LDL-cholesterol in the bloodstream. Unfortunately, this cannot do more than modestly slow the condition; it can't reverse existing plaque to any great degree. By the time a plaque has formed, it has become a self-sustaining lesion, inflamed and attracting ever more immune cells to become overwhelmed by the toxic plaque environment and die, adding their mass to the plaque. The input of LDL-cholesterol from the bloodstream, while creating the t...
Source: Fight Aging! - January 23, 2023 Category: Research Authors: Reason Tags: Daily News Source Type: blogs