Rejuvenation Biotechnology Update for September 2014

The Methuselah Foundation is presently partnering with the SENS Research Foundation to put out a quarterly update on ongoing research for members of the 300. This focuses on work relevant to the end goal of bringing aging under medical control, preventing and curing age-related frailty and disease. Members of the 300 are largely long-standing donors who have pledged to give at least $1000 each year for the next 25 years to fund the work of the Methuselah Foundation. Many of the 300 were early backers and signed up when SENS research was coordinated by the Methuselah Foundation, prior to the SENS Research Foundation spinning off as an independent organization. Their donations still go towards SENS programs even today. Members of the 300 will see their names inscribed on a lasting monument to be raised in the US Virgin Islands, and perhaps more pertinently have access to perks such as glossy updates on SENS research and other insider news from ongoing Methuselah Foundation initiatives.

There are still a very small number of positions left in the 300 - give it some thought. Given just how important funding and public support are for longevity science at this juncture, and the scale of what will be possible with rejuvenation treatments in the future, I'd argue that the 300 is probably the most influential organization that I belong to. The growth in membership was the spur to Methuselah Foundation success a decade ago, and thus the existence of the SENS Research Foundation, as well as a web of other influences on the aging and longevity research community over recent years. This in turn paves the road to a welcome future in which aging no longer causes suffering and death, bringing that era closer than would otherwise be the case. We all make a difference, and every last action counts.

Rejuvenation Biotechnology Update

The Methuselah Foundation is thrilled to partner with SENS Research Foundation in order to bring out the most recent advancements in tissue engineering, regeneration, and rejuvenation research for members of The 300. Because it doesn't take a scientist to understand the vital importance of investing in healthy life extension, these news-letters attempt to frame three significant studies from the past 3-6 months as accessibly and approachably as possible, describing how each one fits into the broader landscape of longevity research.

Regeneration of the aged thymus by a single transcription factor

In this study, the researchers used a genetic switch to induce FOXN1 expression in the thymic epithelial cells of mice, and compared them with mice that did not have FOXN1 induced. They observed that with FOXN1 induction, the thymus was regenerated from progenitor thymic epithelial cells that were still present in the aged thymus. They found that when FOXN1 was induced, the size of the thymus was larger, the expression of genes associated with a young, active thymus was increased, and the production of native T cells was boosted.

Thymic involution is one of the main contributors to declining immune system function with age. In the SENS paradigm, it could be categorized in the class of damage known as "cell loss and tissue atrophy." SENS Research Foundation is currently collaborating with the Wake Forest Institute of Regenerative Medicine on thymic regeneration research. The fact that induced expression of a single transcription factor could have such profound effects on thymic function and T-cell output in aged mice makes this study very interesting. Wouldn't it be nice if we could find a single transcription factor for each organ that, when upregulated, would restore the organ to a "youthful" state?

However, there are some caveats to consider, as one always should with scientific research. One is that, although the researchers did measure T-cell output from the regenerated thymuses of aged mice, they did not test their overall immune function. The quantity of T-cells produced by the regenerated thymuses was increased, but did these T-cells function similarly to young, normal T-cells? It is also prudent to be cautious about the idea of "robust thymus regeneration." In some autoimmune diseases, such as myasthenia gravis, thymic hypertrophy is observed. This kind of autoimmunity might also happen with an approach similar to FOXN1, because the thymus itself, being old, may have other dysfunction besides its reduction in size. Contrast this approach with genuine tissue engineering, where one would receive a new, youthful thymus. More research about thymic regeneration will be needed to determine whether FOXN1 overexpression will contribute to immune hyperreactivity and autoimmunity.

Physiological IgM class catalytic antibodies selective for transthyretin amyloid

TTR amyloidosis is a canonical example of "extracellular junk" - one of the fundamental types of aging related damage that SENS Research Foundation (SRF) attempts to treat. This work was partially funded by SRF, with the goal of finding a reliable way to break down misfolded TTR.

In Alzheimer's disease research, similar strategies of "vaccination" or treatment with antibodies against amyloid plaques have been tried. These treatments yielded some promising results but also some dangerous side effects in a few patients (inflammation of the protective membrane covering the brain). However, there are a few important distinctions between the catabody strategy and the immunization strategy. Perhaps the most notable difference is that catabodies actually break down the target protein (in this case, amyloid aggregates of TTR) themselves, without the requirement for other immune or blood components. Conversely, in previous studies on Alzheimer's disease, the antibodies did not break down ß-amyloid themselves but merely encouraged its clearance through the recruitment of other immune proteins and cells, which also initiates tissue-damaging inflammatory processes. Catabodies may prove to be less inflammatory, since they do not require other immune components to work. Additionally, the dose required for therapeutic effects may be smaller, and potentially less costly to produce.

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