Fight Aging!

The Rejuvenation Biotechnology Update is a collaboration between the Methuselah Foundation and SENS Research Foundation, a newsletter delivered to SENS supporters and members of the Methuselah Foundation 300. The latest edition arrived yesterday, and as usual it is a look at a few of the interesting research results from recent months, with accompanying explanations of their relevance in the bigger picture.

The 300 is a group of donors who have supported the Methuselah Foundation for more than a decade now, and the first members stepped up to help get the first initiatives off the ground back when there were only ideas and intents, longevity science was ridiculed, and funding was scarce. Last year a monument was raised to record the names of the 300, the people who have helped bring about a sea change in the aging research community, the philanthropists who funded the M Prize for longevity science, launched the SENS rejuvenation research programs, delivered seed funding to Organovo, and today support the ongoing New Organ Prizes for tissue engineering. If you want to help speed progress towards a world without aging, in which all age-related disease can be prevented and cured, you could do far worse than to become a member of the 300.

2016 Q1 Rejuvenation Biotechnology Update (PDF)

Transthyretin deposition in articular cartilage: a novel mechanism in the pathogenesis of osteoarthritis.

Transthyretin (TTR) is a protein that normally serves to transport thyroid hormones and the vitamin retinol in the blood. Normally, TTR is dissolved in the blood. However, during aging, some individuals accumulate masses of abnormally folded TTR in their body tissues, a form of amyloid which is associated with impaired organ function. Amyloid aggregates of TTR especially interfere with heart function, and amyloidosis can be fatal in this manner. However, in this study, researchers examined the role that TTR amyloidosis may play in osteoarthritis, a cause of joint pain and inflammation that is common in older individuals. The researchers found that in young individuals, no amyloid deposits were present in the knee joints. Strikingly, however, it was present in 100% of the older individuals with osteoarthritis they examined, as well as in 58% of the older individuals without osteoarthritis in their study.

Although there were only a small number of people in this study, the results are interesting, and underscore the importance of the development of therapies for TTR amyloidosis. TTR amyloidosis appears to contribute substantially to increased mortality at advanced ages. TTR amyloidosis of the heart affects a quarter of those who are age 80 and older, and we are only recently learning that it is also present in other parts of the aging body. Some evidence suggests that TTR amyloidosis may be the main cause of death in individuals over the age of 110. Now, with this study, we can see that TTR may contribute to osteoarthritis too, which implies that a significant increase in quality of life could be obtained - along with potentially increased longevity - if treatments for TTR amyloidosis could be developed. Accordingly, SENS Research Foundation has been pursuing and funding a project to develop catalytic antibodies to break down TTR amyloid deposits.

GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration

There have recently been several exciting reports about the apparent positive effects of GDF-11 in aged animals. A recent paper has reported some observations about GDF-11 that are the opposite of prior reports. It is this controversy which we highlight. GDF-11 is similar in structure to several other proteins, including myostatin (also called GDF-8), a circulating protein which is known to inhibit muscle growth. The current paper of interest alleges that the antibodies used to detect GDF-11 in previous studies were not specific to GDF-11 and were cross-reacting with myostatin. This, the authors allege, led previous investigators to misinterpret the actual concentration of GDF-11 in their experiments. In contrast to these earlier studies, the authors observed an increase in both GDF-11 and myostatin with age using their reagents, and wrote that GDF-11's function is likely redundant with that of myostatin and could be targeted for blockade to treat age related decline in skeletal muscle mass.

This seems like a complicated story with many contradicting results from different groups. It highlights a couple of key points: (1) The importance of scientific dialog and discourse to sort out apparently contradicting results like this, (2) The importance of making sure that research reagents such as antibodies and primers used to detect specific proteins are actually specific for what researchers want to measure, and (3) The idea of a U-shaped dose-response curve for biological molecules, which is one of the many difficulties of trying to tweak metabolism to inhibit the aging process instead of repairing the damage directly.

Once the antibody specificity issue is sorted out, we will need to learn about the true effects of GDF-11 at a range of doses. It is possible that apparently contradictory results were obtained due to different doses of GDF-11 being used in the studies. There may be a "U-shaped" curve of GDF-11 where the optimal amount lies in the middle, and much more or much less could have vastly different effects. Or, it may be that we have yet to discover additional, harmful effects of GDF-11, or that its effects are similar to myostatin as some groups have reported. As with many processes in the body, having too much or not enough of something can have profoundly negative effects, and nothing produced by metabolism is without the potential for harm.