The effects or Inflammation and the effect it has on the immune system are discussed in this article at FightAging!

With age, the immune system falls into a state of ever increasing chronic inflammation, a process known as inflammaging: the immune system is overactive, but nonetheless declines in effectiveness at the same time. Researchers here consider how inflammaging can damage the bone marrow stem cell populations responsible for generating immune cells, possibly the basis for a vicious cycle in which the failures of the immune system feed upon themselves to accelerate age-related damage and dysfunction.

Hematopoiesis is an active, continuous process involving the production and consumption of mature blood cells that constitute the hemato-lymphoid system. All blood cells arise from a small population of hematopoietic stem cells (HSCs) in the bone marrow (BM) that have two unique properties: self-renewing capacity, the ability to generate themselves, and multi-lineage differentiation capacity, the ability to produce all blood cell types. Since, in the steady state, most adult HSCs are in the G0 phase of the cell cycle, i.e., they are quiescent and are estimated to turnover slowly on a monthly time scale, daily hematopoietic production is mainly sustained by highly proliferative downstream hematopoietic progenitor cells (HPCs).

Aging of the hematopoietic system is represented by functional declines in both the adaptive and the innate immune system, an immunosenescence that leads to high susceptibility to infections, low efficacy of vaccinations, and increased vulnerability to the development of autoimmunity and hematologic malignancies. It has been show that (a) B cell production decreases significantly with advancing age, i.e., the naive B cell pool diminishes, while the memory B cell pool expands. Diversity of the B cell repertoire also decreases in association with lowered antibody affinity and impaired class switching. B cells are prone to produce auto-antibodies increasing the incidence of spontaneous autoimmunity; (b) de novo T cell production also declines with aging partially due to thymic involution.

Great news for SENS Research and Rejuvenation Biotechnology.

One of the biggest highlights of the year for us has got to be Internet Entrepreneur Michael Greve committing $10 million to SENS-related research and startups. A list of some of the projects he is supporting can be found at the Forever Healthy Foundation. We are so pleased to have the support of Michael and his team in the mission to bring rejuvenation biotechnology to the world.

“In order to accelerate the access to healthy longevity for all of us we directly fund cutting-edge research on molecular and cellular repair to combat the root causes of aging and support the creation of startups turning that research into therapies for human application.” — Michael Greve.

#aging #sens

Senolytics moving into human clinical trials in the next 18 months! One of the greatest pieces of biotech news of 2016.

The Silicon Valley drugmaker is part of a wave of new companies chasing after the fountain of youth.

By Caroline Chen Bloomberg

More progress with cancer and using a similar approach to senolytics, no surprise really as cancer and senescent cell share a lot of common ground and approach that work with one may well work with the other if they are aimed at inducing apoptosis.

Apoptosis, or programmed cell death, is a rapid and irreversible process to efficiently eliminate dysfunctional cells. A hallmark of cancer is the ability of malignant cells to evade apoptosis.

Dr Luminita Paraoan, from the University’s Department of Eye and Vision Science in the Institute of Ageing and Chronic Disease, has published new findings in the British Journal of Cancer that identify the requirement of a protein called p63 for the initiation of apoptosis in UM.

Chromosome 3 is one of the 23 pairs of chromosomes in humans. People normally have two copies of each chromosome. One part of chromosome 3 contains the gene for the protein p63. Unfortunately people with aggressive (resistant to apoptosis) UM do not have this part and therefore do not have the p63 protein.

The Goldilocks zone with telomere length is the key.

Ever since researchers connected the shortening of telomeres—the protective structures on the ends of chromosomes—to aging and disease, the race has been on to understand the factors that govern telomere length. Now, scientists at the Salk Institute have found that a balance of elongation and trimming in stem cells results in telomeres that are, as Goldilocks would say, not too short and not too long, but just right.

The finding, which appears in the December 5, 2016, issue of Nature Structural & Molecular Biology, deepens our understanding of stem cell biology and could help advance stem cell-based therapies, especially related to aging and regenerative medicine.

“This work shows that the optimal length for telomeres is a carefully regulated range between two extremes,” says Jan Karlseder, a professor in Salk’s Molecular and Cell Biology Laboratory and senior author of the work. “It was known that very short telomeres cause harm to a cell. But what was totally unexpected was our finding that damage also occurs when telomeres are very long.”