Lifeboat Foundation

We recently had the opportunity to interview Dr. Amutha Boominathan from the SENS Research Foundation, at the Ending Age-Related Diseases 2019 conference about her research on mitochondrial repair therapies, the value of animal models, and her views on the future of aging research.

Dr. Amutha Boominathan received both her MSc and her PhD in Biochemistry from the University of Pune and the National Chemical Laboratory in India, respectively. She went on to do postdoctoral work in the U.S. relating to mitochondrial biogenesis at U. Penn and Rutgers University. She has extensively studied mechanisms of fusion and fission in mitochondria, Fe-S cluster biosynthesis, and protein import into mitochondria as part of her postdoctoral fellowship with the American Heart Association.

Currently, Amutha leads the MitoSENS program at SENS Research Foundation in Mountain view, California. Her research group is focusing on understanding mitochondrial DNA (mtDNA) mutations and restoring lost functionality as a result of these mutations by way of the allotopic expression of mitochondrial genes. Inherited mtDNA mutations can result in severe and debilitating diseases, such as NARP, Leigh’s syndrome and MELAS. Even in otherwise healthy individuals, mtDNA mutations accumulate with age. The MitoSENS team has already succeeded in stably expressing the ATP8 gene using their method and is looking forward to tackling each of the 13 mitochondrial protein genes in the coming years. Its goal is to develop safe and effective gene therapies for mitochondrial dysfunction.

The SENS Research Foundation science team is taking the next step in their work on moving mitochondrial genes into the cell nucleus, a process called allotopic expression. Having proven that they can carry out this task with the ATP8 gene in cells, they are now aiming at proof of principle in mice. This will require the production of transgenic mice, using a novel technology funded by the SENS Research Foundation called the maximally modifiable mouse. This mitochondrial project is being crowdfunded at Lifespan.io: you, I, and everyone else can contribute to advancing the state of the art one step further towards eliminating mitochondrial DNA damage as a cause of aging.

Mitochondria are the power plants of the cell, a herd of organelles descended from ancient symbiotic bacteria. They reproduce by replication and are recycled when damaged by cellular maintenance processes. Mitochondria carry the remnant of the original bacterial DNA, encoding thirteen genes vital to the process by which mitochondria package chemical energy store molecules. Unfortunately mitochondria generate reactive molecules as a byproduct of their operation, and this DNA is less well protected than the DNA of the cell nucleus. Some forms of damage to this DNA can break mitochondrial function in ways that allow the broken mitochondria to outcompete their functional peers, leading to dysfunctional cells that export massive quantities of damaging, oxidative molecules into the surrounding tissue. This contributes to conditions such as atherosclerosis, via the production of significant amounts of oxidized cholesterol in the body.

Allotopic expression of mitochondrial genes will work around this issue by providing a backup source of the proteins necessary to mitochondrial function. It has been demonstrated to work for ND4, and that project has been running for some years at Gensight Biologics to produce a therapy for inherited conditions that involve mutation of that gene. This work must expand, however, to encompass all thirteen genes of interest. So lend a hand, and help the SENS Research Foundation team take the next step forward in this process.

Flushing harmful zombie senescent cells from the body that have become old, fatigued and have ceased to divide has become one of the more prominent proposals in the anti-aging sphere. The hypothesis has generated a stream of animal data to support the theory, and now the Mayo Clinic has results from a human study that suggests they have found drugs that can do the same.

While the main goal of the Phase I trail was not to show the effects of reducing senescent cells in the body the researchers were eager to show that the anti-aging senolytics that were tested in animal studies can work the same way in humans as “so far, there has been no direct demonstration of senescent cell clearance by senolytic drugs in peer-reviewed published human clinical trials,” the authors wrote in EBioMedicine, despite the publication of the first human data in January.

Dasatinib and quercetin were given to 9 patients with diabetes related chronic kidney disease for 3 days in this trial. The drugs cleared participants systems in a matter of a few days, but the effects persisted and the authors reported, “Key markers of senescent cell burden were decreased in adipose tissue and skin biopsied from subjects 11 days after completing the 3-day course of D + Q, as were key circulating SASP factors, compared to before administration of these senolytic drugs.”

It takes something truly extraordinary, like maybe the death of the Sun, to kill the near-indestructible invertebrate known as the tardigrade. Crash-landings on the Moon, a lack of oxygen and conditions in the darkest corners of the ocean don’t appear pose a threat to this critter’s livelihood. Scientists studying these so-called water bears have uncovered a neat trick they employ to endure inhospitable conditions, using a unique protein to generate protective clouds around their DNA.

Tardigrades measure no more than a millimeter long, but possess an indomitability that would make even nature’s largest and hardiest creatures jealous. Key to their survival is an ability to enter a suspended and extremely dehydrated state of being called anhydrobiosis, in which their metabolism is put on hold until the surrounding conditions are more favorable to a regular life.

This capability has seen tardigrades endure temperatures as high as 150º C (302º F) and as low as −272º C (−457.6º F). It has seen them studied in the vacuum of space and exist amongst intense pressures at the bottom of the ocean. When an Israeli spacecraft carrying tardigrades crash-landed on the Moon in August, it inspired some dramatic headlines around the possibility of the near-indestructible creatures colonizing Earth’s only natural satellite.

Radio program The Current had me on this morning discussing #transhumanism, specifically #robots & #AI running for political office. It’s Canada’s most listened to radio program with millions of listeners. Here’s a fun write-up of it:

We ask if we should ditch flesh-and-blood politicians, and give the robots a go at leadership.

A trio of researchers from the U.S. and the UK has won the 2019 Nobel Prize in Medicine, the first of five prizes to be announced this week. On Monday in Sweden, the Nobel committee announced that Americans William Kaelin Jr. and Gregg Semenza, along with Peter Ratcliffe, would split the nearly million-dollar prize for their work in unraveling a fundamental aspect of life: how our cells keep track of and respond to fluctuating oxygen levels.

This year’s prize was decades in the making.

Though we’ve long known that our cells need oxygen to produce energy and keep us alive, we were largely in the dark on how cells sensed oxygen, or how they managed to adapt in times of low oxygen, a state known as hypoxia. In the early 1990s, Gregg Semenza, currently of Johns Hopkins University, and his team discovered some of the key genetic machinery that cells use to detect hypoxia and then respond by producing a hormone called erythropoietin (EPO).

William Kaelin, Sir Peter Ratcliffe and Gregg Semenza worked out how cells adapt to oxygen availability.

A series of clinical trials have tested an experimental treatment for Parkinson’s disease that uses a novel approach: administering the drug straight into the brain via implanted ports. The leading researchers believe this may be a “breakthrough” therapeutic strategy for neurological conditions.

Newly trialed therapy could launch a fresh chapter in the treatment of Parkinson’s disease.

In a new series of studies that culminated with an open-label trial (where participants were aware of what treatment they would receive), scientists have begun testing the effectiveness of a new treatment — and method of delivery — for Parkinson’s disease.

Circa 2017

The cells are converted by a small microchip, similar in size to a penny, which injects genetic code into skin cells, transforming them into other types of cell.