The Methuselah Foundation and SENS Research Foundation collaborate to put out a quarterly newsletter on recent scientific advances for members of the 300, people who pledge to donate $25,000 over 25 years to research and development aimed at extending healthy life spans. The earliest members of the 300 collectively gave the first significant funding to the Methuselah Foundation when it launched, providing the resources needed to start the Mprize for longevity science and later the SENS rejuvenation research programs.

SENS research outgrew its roots and spun off into its own non-profit foundation back in 2009, but the staffs of the Methuselah Foundation and SENS Research Foundation continue to collaborate on various ventures. We're all chasing the same goal, after all, meaning the development of therapies that can collectively halt degenerative aging by periodically repairing its root causes. This class of technology can in principle prevent and cure all age-related disease: it is just a matter of building tools that are good enough at the various necessary forms of cell and tissue repair.

This quarter's newsletter turned up in my inbox today alongside a reminder that the Rejuvenation Biotechnology 2015 conference to be held on August 19th in San Francisco is still accepting registrations. Just as last year, this will be a meeting in the middle between industry and academia, building the bridges needed for the near future development of first generation rejuvenation therapies. The times are changing, and this will be just one of a range of well-subscribed events taking place each year, attended by people with a serious focus on the treatment of aging.

Rejuvenation Biotechnology Update, July 2015 (PDF)

The authors showed that in older mice, and in humans, evidence of damage to the pancreatic islet blood vessels could be observed. They took pancreatic islets from old mice and transplanted them into the eyes of young mice whose own β-cells had been destroyed with a drug so that they could produce no insulin on their own (a common model of "type 1" or "juvenile" diabetes). Remarkably, when placed in the environment of the young mouse eye, the islets from the old mice proliferated, developed a healthy blood supply, and were able to completely restore control of blood glucose and function as normal β-cells would in the young, type 1 diabetic mice. As strange as it sounds, these β-cells were able to do this from inside the eye.

This study is very provocative. Similarly to parabiosis experiments, removing aged pancreatic islet cells from their original host and exposing them to the younger host's intact blood vessels was able to restore their normal function. This lends credence to the idea that, at least in the case of pancreatic β-cells and diabetes, the aged tissue environment and not the aged cells themselves is the important determinant of functionality. As the authors point out, this finding provides hope that finding ways of restoring the vasculature of the pancreatic islets to a healthier state could be key in treating age-related type 2 diabetes/glucose homeostasis problems.

Scanning Ultrasound Removes Amyloid-β and Restores Memory in an Alzheimer's Disease Mouse Model

The researchers in this study found a non-pharmaceutical and non-invasive way to stimulate clearance of amyloid-β (Aβ) in the brains of AD mice. Repeated treatments with scanning ultrasound after injecting "microbubbles" of air into the blood of AD mice were able to induce movement of Aβ into the lysosomes (the "cellular incinerator") of microglia (cells that perform cleanup, among other functions, in the brain) in the brains of these mice. Meaningfully, the AD mice who received the ultrasound treatments showed improvements on three different memory tests compared to the control group.

The approach used in this study is very interesting because it does not rely on pharmacological or surgical means, but was able (at least in AD mice) to induce clearance of Aβ from the brain and improvements in memory. The mechanism may lie in the ability of the microbubbles in the blood to vibrate against the lining of the small capillaries in the brain, causing a gentle and temporary disruption of the blood-brain barrier and possibly allowing antibodies or other blood components to access the brain.

There are a few caveats, one of which is how well AD mice accurately model human AD. Many of these mice are genetically altered to produce large amounts of Aβ, and consequently develop symptoms similar to human AD, such as memory decline. But in humans, the majority of cases are not caused by a single genetic mutation. Another caveat: there is always the possibility that brain ultrasound could induce some kind of side effect in humans not observed in the mice, such as microvascular strokes, hemorrhaging, or inflammation - or that it would simply be ineffective because the ultrasound could not penetrate deep enough into the brain tissue of a human as could be done in a mouse with a comparatively tiny cranium and thin skull.

α-Synuclein Inclusions in the Skin of Parkinson's Disease and Parkinsonism

Several degenerative brain diseases (Parkinson's Disease, Dementia with Lewy Bodies, Multiple System Atrophy, and others) share the common feature of protein aggregates (clumps) in the brains of patients, made of a protein called α-synuclein. These diseases are sometimes collectively referred to as "synucleinopathies." Since there are two vaccines currently in human clinical trials that are aimed at clearing α-synuclein aggregates (which will hopefully lead to restoration of function), and α-synuclein aggregates are known to be associated with functional impairments in people who have not yet developed full-blown PD or related disease, it would be useful to have a non-invasive test to determine who might need such a treatment, especially if this can be determined before overt disease develops.

There is a hypothesis that while α-synuclein may ultimately aggregate in the brain in PD, it may originate from other sources in the body, such as the gut. The fact that α-synuclein was found in the skin of a majority of PD patients tested is interesting, and it may even provide some basis for speculation that α-synuclein could come from the skin, or from multiple sources, migrate to the brain, and cause Parkinson's Disease. Skin and neural tissue share a common embryonic origin (the ectodermal germ layer), so both cell types may share some genetic program that leads α-synuclein production and accumulation. But this is all just speculation right now, and as is often the case with diseases of aging, it can be very difficult to determine the relationship between various factors and observations.