Methuselah Foundation and SENS Research Foundation are presently partnering to issue a quarterly update on rejuvenation biotechnology research to members of the 300, each of whom has committed to donating $25,000 over 25 years to help fund the development of effective treatments for degenerative aging. The last time I checked, there were in fact very nearly 300 members of the 300 - just a few places are left. It is a great initiative that helped launch the Methuselah Foundation more than ten years ago and raised the first significant funds for the Mprize for longevity science and early SENS research. You might read Michael Rae's 2004 essay "Why I Joined the Three Hundred" for more on that topic.
I am a member of the 300 myself, and consider it money well spent. The Methuselah Foundation has engineered a great deal of beneficial change in the aging research and related medical development communities over the years, all of it funded by philanthropic donations. It is no coincidence that prior to the Foundation's existence the research community and funding institutions were a mix of hostile and dismissive towards research aimed at extending healthy life spans, whereas today the prevailing culture is much more accepting of that goal. A lot of work behind the scenes aided in accomplishing that transformation.
The first edition of the present quarterly rejuvenation biotechnology newsletter was sent out back in January, so consider this a reminder if you didn't get around to reading it. Here is a link to the latest:
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 newsletters 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.
This study shows that this strain of immune-deficient mice is able to receive a transplant of human immune stem cells, and to live longer-term with a "humanized" immune system where part of the immune cells in the mouse are derived from humans. One interesting aspect of this study is that it suggests that parts of the immune system might be able to be rejuvenated in a persistent way using human progenitor/stem cells. This is exciting because of the observation that the virus, cytomegalovirus or "CMV," appears to contribute to human immune senescence by reducing the proportion of naive T cells in aging. Moreover, thymic involution, the reduction in size and function of the thymus, has been observed in human aging. This is also assumed to contribute to reduced immune function in human aging.
The animal model in this paper could also be very useful as a tool for studying the effects of aging on the human immune system, while still using mice as the subjects, which are easier to use in research because of their small size, well known genetics, fast reproduction, and because they are mammals.
In this study, the researchers used a proprietary 3D bio-printing technology to create liver constructs that simulate a human liver environment. They started by using hepatocytes (liver cells), and then added other cell types found or near in the liver. These cells began to integrate and interact with one another to create a kind of "simulated liver." They then tested this "liver simulation system" by testing for activity of a critically-important liver enzyme family involved in drug metabolism and detoxification of substances foreign to the body. They also tested whether these integrated cell systems would die quickly or live and function for a prolonged period of time, and they observed healthy, persistent functioning.
The drug development and approval process is immensely burdensome, time-consuming, and expensive. A very large proportion of this cost is due to the rigorous human testing that must be done to ensure the drug's safety. We're excited to see the advancement of biologically-relevant drug-testing systems by which drug companies can rigorously test small molecules without harm to living humans. These kind of "human simulations" can be valuable because they may dramatically reduce the cost of testing and ultimately deliver successful, safe drugs to people who need them, both more cheaply and more quickly.
The subject of this study involved a compound intimately involved in the biochemistry of creating energy in our bodies. This particular compound is called "nicotinamide adenine dinucleotide", or "NAD+". NAD+ is well-known for its involvement in many biological processes involved in energy transfer, including those in the mitochondria. NAD+ has been observed to decline during advancing age, as is mitochondrial function. Knowing NAD+ is so closely involved in mitochondrial function suggests that if one were to replenish NAD+ in old age, one might also restore mitochondrial function. This might have quite a number of benefits, because doing so could enhance energy production in the body's cells, thereby possibly enhancing muscular function, brain function, and exercise output, among other things. For example, calorie restriction, which has been observed to "slow" various aspects of aging in many different organisms, appears to preserve both NAD+ concentrations and mitochondrial function during aging.
SENS Research Foundation (SRF) has a research program dubbed "MitoSENS" that addresses a different reason for age-related mitochondrial dysfunction. The present study focuses on a reversible decline in energy production capacity across most cells in the aging body due to altered metabolism, and reports that raising NAD+ in old mice improved mitochondrial function to that of young mice. SRF is more concerned about a tiny minority of cells in the body that harbor irreversible deletions in mitochondrial DNA, which push the cells into an abnormal metabolic state that ultimately causes them to poison far-flung cells all across the body. There is no reason to think that [a NAD+ boosting] treatment would have any positive effect on the underlying mitochondrial DNA deletions. If it did not, these may still need to be properly addressed to achieve persistent and complete human rejuvenation.