Rejuvenation Biotechnology Update for Q2 2015

The Methuselah Foundation and SENS Research Foundation collaborate to put out a quarterly newsletter 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 300 are the individuals that kick-started the Methuselah Foundation more than a decade ago, when it was just a few determined individuals setting out to change the aging research community from the outside, back before SENS research programs were any more than a vision statement, and when talking about extending healthy life spans was frowned upon by gerontologists. A great deal has changed since then. The tenor of the research community is very different today, many scientists and philanthropists talk openly about tackling aging as a medical condition, and a great deal of early stage progress has been made in the laboratory. Something approaching $30 million dollars has been raised by the Methuselah Foundation and SENS Research Foundation since the early days and invested in SENS, organ engineering, and diverse other initiatives in longevity science.

The quarterly Rejuvenation Biotechnology Update is aimed at keeping people in the loop, those who support the end goal but who don't keep up with research news on a week to week basis. It is good to show that progress is underway, that the funding provided to the Methuselah Foundation and SENS Research Foundation is not just used well in the immediate sense, but that it is also inspiring greater funding and progress on the part of other organizations and research groups. There are more than enough resources and researchers in the world to defeat aging within our lifetimes via repair strategies such as SENS if people put their minds to it, if a grand scientific endeavor of a size comparable to the stem cell or cancer research fields is formed soon enough. The real challenge at this stage lies in persuasion, spurring the will and the choice to seek greater healthy longevity and the defeat of aging.

Rejuvenation Biotechnology Update, April 2015 (PDF)

The Achilles' Heel of Senescent Cells: From Transcriptome to Senolytic Drugs

As organisms age, cells begin to accumulate that display a specific phenotype termed "senescence." Senescent cells do not divide, but they also do not carry out their normal function, and do not die. This may not be much of a problem in and of itself, except that these cells are not just passive bystanders, harmlessly "hanging around." Rather, they secrete hormones and cytokines that influence the surrounding tissue and the organism as a whole, and may increase inflammation and make the organism more prone to the development of cancers and other diseases. Specific examples of cell types that can become problematic senescent cells include those in human fat, skin, and connective tissue throughout the body. One goal of SENS Research Foundation is the development of ways to remove senescent cells.

In this study, researchers tested two drugs, quercetin and dasatinib, and found that they killed senescent cells, first in cell culture, then in mice who had a high burden of senescent cells because of being chronologically aged, exposed to radiation, or carrying a genetic mutation. More importantly, the killing and removal of senescent cells by these drugs in the mice led to functional improvements, such as better cardiovascular function, improved limb strength, and an increase in their "healthspan," or healthy life.

This finding is exciting. The two drugs tested in this study, quercetin and dasatinib, each had different "profiles" of which senescent cell types they were most effective at killing. They were tested in the mice in combination, but it is also conceivable that each might be effective individually. We are eager to see future studies reveal additional compounds that can eliminate other specific types of senescent cells. New drugs could then be combined with the two tested here for an even more powerful drug regimen that "covers all the bases" in getting rid of many types of senescent cells. Alternately, the drugs could be used individually in a personalized medicine approach, depending on what type of senescent cells are most problematic for the human patient. The ability to remove senescent cells in humans could be expected to affect tissues such as skin, fat tissue, and connective tissue, and may reduce body-wide inflammation, thereby potentially improving inflammatory conditions.

New α- and γ-Synuclein Immunopathological Lesions in Human Brain

Several degenerative brain disorders (sometimes collectively referred to as "synucleinopathies") are defined by the presence of clumps of a protein called α-synuclein. Recent evidence has surfaced (for a detailed summary, see "Bold Leaps Forward for α-Synuclein Immunotherapy") indicating that α-synuclein aggregates are not only involved in diseases which feature Lewy Bodies, but also in functional impairments in humans who have not yet developed these diseases. There are two vaccines currently in human clinical trials, aimed at clearing α-synuclein aggregates, which will hopefully lead to restoration of function. This is an area of particular interest for SENS Research Foundation, since one of the main strategies in the SENS platform is the cleanup of "intracellular junk," such as protein aggregates like α-synuclein and β-amyloid. This strategy follows from the general principle that underlies all SENS strategies: identify aging damage in the body, and repair the damage once it is present.

This study suggests that in addition to α-synuclein, γ-synuclein or hybrid α-/ γ-synuclein aggregates could be targeted for cleanup to treat synucleinopathies, or even restore the integrity of the brain in aging people who can't be formally diagnosed with these diseases. It remains to be seen whether doing so would be able to restore normal function to the brain in cases where an overt disease like Parkinson's has developed, but results from studies where vaccines were used to induce the organism's immune system to clear α-synuclein aggregates from the brain suggest cause for cautious optimism.

Whole Genome Sequencing of the World's Oldest People

In this study, researchers sequenced the genomes of 17 people who were over the age of 100. These individuals' ages were validated by documents such as birth certificates, marriage certificates, or current passports (an important step; it can be difficult to verify the ages of very old individuals because analog records are easily lost over time or contain erroneous information). They compared their genomic sequences, looking for any genetic variants that changed the structure of a protein and were found among the cohort of supercentenarians, but not in a control group who did not live over 100 years. The authors did not find any such genetic variants.

Although the authors did not find a specific gene variant associated with extreme longevity, their findings could be interpreted in a very hopeful way: this study provides evidence that it is not necessary to have been lucky enough to be born with some specific genetic variant in order to become a supercentenarian. We don't know what genetics confer the best chance of a long life, but at least we haven't yet found any gene that rules us out from having the chance to become a supercentenarian if we lack it.

Comments

This was exciting to read, the latest update in the Methuselah Foundation and SENS Research Foundation. I have read a lot lately (mostly through this blog) about getting rid of senescent cells.

Can anyone hazard a guess on when this could be tried (clinical study) on a person. I assume it would be done outside the U.S. I think the sooner it could be done and is successful, the quicker the publicity and a surge of funding will follow. I'd like to think it could be done within 5 years, but maybe I am too optimistic?

Posted by: Robert Church at April 23rd, 2015 8:02 PM

The biggest barriers are funding, there are lots of researchers I talk to who would like to research and conduct studies into various methods but there is no funding to do so. End result is they waste time investigating calorie restriction and other wastes of time instead of interventions that are meaningful.

The other huge barrier is the current medical system which is based on profiteering, mind numbingly slow research and miles of red tape. ~15 years and around a billion + dollars to bring a single treatment to market is frankly a joke. No wonder companies are moving offshore to avoid this and I predict gene therapy and other rejuvenation therapies will likely begin outside the US/EU because of the present situation.

Posted by: Steve H at April 24th, 2015 2:03 AM

Senolytics is a very promising area though and I think along with Telomere rejuvenation will probably arrive as some of the first therapies. Its a shame it will probably take 10+ years under the FDA unless it gets fast tracked.

Posted by: Steve H at April 24th, 2015 2:12 AM

Thanks Steve for your input.

It is quite disappointing the U.S. (FDA) is not supportive of saving lives due to being overly cautious, thus dragging their feet.

And, thanks Bush for stopping Embryonic stem cells for 8 years so now we have to play catch up.

We are even getting behind on the drone delivery industry due to FAA dragging their feet so Amazon is going elsewhere first.

Yea, I can see myself doing the medical tourism in the next 10 years or so.

Posted by: Robert at April 24th, 2015 12:10 PM

"This is an area of particular interest for SENS Research Foundation, since one of the main strategies in the SENS platform is the cleanup of "intracellular junk," such as protein aggregates like α-synuclein and β-amyloid."

Isn't this a typo in the report. It should be written intercellular junk shouldn't it?

Posted by: Jim at April 26th, 2015 3:40 AM

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