Read More at Fight Aging! The hematopoietic cell populations of the bone marrow are responsible for producing red blood cells and immune cells. With advancing age, the production of immune cells shifts to bias myeloid cells of the innate immune system versus lymphocyte cells of the adaptive immune system. This is thought to be an important aspect of immune aging. Researchers here attempt to reverse this myeloid bias in immune cell production by selectively destroying some of the myeloid-focused hematopoietic cells, an interesting idea. The results are positive and intriguing. During aging, the number of hematopoietic stem cells (HSCs) that make balanced proportions of lymphocytes and myeloid cells decline, while those that are myeloid-biased increase their numbers. This favors the production of myeloid cells. Early in human history, when people rarely left their birthplace and lived shorter lives, this gradual…
Reversal of Markers of Aging in Cells Following Small Molecule Partial Reprogramming
Read More at Fight Aging! Partial reprogramming by exposure to Yamanaka factors resets many of the epigenetic changes characteristic of cells in aged tissue. This is a potential approach to the production of future rejuvenation therapies. At present, some research groups are attempting to move away from genetic interventions to find small molecules that can provoke reprogramming. There are some avenues that seem promising. Here, researchers assess the effects of partial reprogramming by small molecules on a range of omics data and functional parameters for cells, finding that the outcomes are much as one would expect for a successful protocol. Partial reprogramming by cyclic short-term expression of Yamanaka factors holds promise for shifting cells to younger states and consequently delaying the onset of many diseases of aging. However, the delivery of transgenes and potential risk of teratoma formation present challenges…
Problematic B Cells Accumulate in Visceral Fat and Indirectly Provoke Inflammation
Read More at Fight Aging! The authors of today’s open access paper present an interesting and novel way in which visceral fat tissue provokes chronic inflammation. It has been noted that dysfunctional B cells accumulate with age. Here, dysfunctional B cells of a specific subtype are shown to accumulate in aged visceral fat tissue, acting to provoke other immune cells in visceral fat tissue, such as macrophages, into a more pro-inflammatory state. The researchers demonstrate that removing the B cell population helps to reduce the age-related inflammation generated by visceral fat by removing the contribution to inflammatory macrophage behavior. Of note, B cells regenerate quite rapidly following clearance, and it seems that using pharmacological means or gene therapies to clear out B cells in aged individuals would improve a number of issues. Targeted clearance of specific immune cells (such as…
Regulatory T Cells Contribute to Reduced Myelination in the Aging Brain
Read More at Fight Aging! Myelin surrounds the axons that connect neurons to one another, and is required for the transmission of electrical impulses. This myelin sheath is maintained by oligodendrocytes. These cells do not carry out their work in isolation; a great many factors are involved in determining the size and capabilities of the oligodendrocyte population. Aging is disruptive to the myelination carried out by oligodendrocytes. The consequences are not as bad as the profound loss of myelin that takes place in demyelinating diseases such as multiple sclerosis, but age-related loss of myelination does appear to degrade cognitive function. Researchers are thus interested in understanding the mechanisms involved, in search of ways to restore a youthful capacity for myelination in the aging brain. Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis, however,…
Vascular Smooth Muscle Cells Become Prone to Altered Behavior with Age
Read More at Fight Aging! The altered signaling environment in aged tissue produces changes in cell behavior, some of which is adaptive and helpful, and some of which is maladaptive and harmful. In some cases the same process can be one or the other depending on context. Cellular senescence, for example, is helpful in the contexts of cancer suppression and regeneration from injury, but only up until the point at which senescent cells are no longer removed as rapidly as they are created, at which point their continued, unrelenting pro-growth, pro-inflammatory signaling contributes to many of the forms of tissue dysfunction observed in aging. Vascular smooth muscle is vital to the operation of the vasculature, determining blood pressure via appropriate contraction and dilation of blood vessels in response to environmental cues. Today’s open access paper is focused on the ways…
Antigen Presenting Cells Donate Telomeres to T Cells to Increase their Longevity
Read More at Fight Aging! T cells replicate aggressively in response to infection and other threats, yet these cells must also persist in the body for years in order to maintain immunological memory. Telomeres, repeated DNA sequences at the ends of chromosomes, shorten with each cell division. This mechanism forms a part of the Hayflick limit on somatic cell replication. When telomeres become too short, cells become senescent and self-destruct, or are destroyed by immune cells. T cells can employ telomerase to lengthen telomeres, but not to any great degree. So how do they manage such long lives in an environment of repeated threats by pathogens, and thus repeated bursts of telomere-shortening replication? In today’s open access paper, the authors outline a fascinating mechanism by which antigen-presenting B cells, which interact with T cells to coordinate the immune response, donate…
β2-microglobulin in Buccal Cells as a Biomarker of Aging
Read More at Fight Aging! Researchers here note that expression of β2-microglobulin rises with age in cells of the inner cheek, correlating with p16 expression, a marker of cellular senescence. β2-microglobulin is connected to inflammation, and senescent cell burden is one of the more important contributions to the chronic inflammation of old age. One can never have too many biomarkers of age, even if they are individually only loosely correlated with age, as combining them can in principle produce better and more accurately correlated metrics. β2-microglobulin (β2M) is a small protein that is expressed in all nucleated cells, previous data showed that its activity increases during inflammation. β2M interplays with cytokines for instance, IL-6, IL-8 and others intracellularly to induce inflammatory responses. In addition, it can bind and modulate the activity of growth factors and hormones and receptors. β2M has…
Much Yet to Establish Regarding the Role of Regulatory T Cells in Immune System Aging
Read More at Fight Aging! Regulatory T cells, as the name might suggest, are involved in controlling the immune response, particularly damping it down at the point at which it should resolve. They also prevent an inflammatory response from starting when it would be harmful or unnecessary, such as in response to self-antigens. A failure of regulatory T cell function is likely involved in autoimmunity, as well as in the chronic inflammation of aging. As today’s open access paper notes, regulatory T cells may be both harmful and helpful in older individuals, attempting to suppress inappropriate inflammation, but also becoming dysfunctional in ways that both suppress appropriate immune responses to infection and allow autoimmune conditions to arise by failing to suppress the response to self-antigens. Yet all too little of this is certain in the details, and published studies provide…
Germline Stem Cells in Ovaries and Female Reproductive Aging
Read More at Fight Aging! In today’s open access paper, researchers discuss the evidence for the existence of germline stem cells in the ovaries, responsible for maintaining fertility in the usual manner of stem cells, by generating daughter cells that replace losses and ensure function. Is ovarian aging, leading into age-related infertility, much accelerated over the aging of other organs in our species because this stem cell population loses function more rapidly than those in other tissues? That is a reasonable hypothesis, and some of the possible mechanisms are discussed. That overies are a hypoxic environment to begin with, and that supply of oxygen and nutrients does tend to decline with age for a range of reasons, is one of the more intriguing ideas. A number of groups, including a few biotech startups in the growing longevity industry, appear to…
Transplanting B Cells from Old Mice to Young Mice to Investigate Details of B Cell Aging
Read More at Fight Aging! The varieties of B cell in the immune system participate in the immune response to pathogens by creating antibodies to match specific antigens, and spreading the information represented by that antibody to portions of the adaptive immune system capable of attacking threats. This is a very crude, high level summary of an enormously complex system. The fine details of how subsets of the B cell population generate suitable antibodies, and then communicate with one another and the rest of the immune system, are complicated indeed, involving many different subsets of cell, different paths of activation, and different mechanisms. Aspects of B cell function are known to decline with age, contributing to the broader loss of efficacy in the immune response, the onset of immunosenescence. Is this a problem with the B cells themselves becoming changed…