The SENS Research Foundation is the leading coordinator of rejuvenation research: funding and organizing scientific programs with the aim of reversing degenerative aging and preventing age-related disease. This can be achieved through the development of biotechnologies capable of repairing the identified forms of cellular and molecular damage that cause aging. Some of these biotechnologies are within just a few years of proof of concept treatments deployed in the laboratory, given fully funded research programs. Sufficient resources for such rapid progress are lacking, however: rejuvenation research of this sort is entirely funded by philanthropy at the present time, ignored by more mainstream sources of research funding.
One of the programs run by the SENS Research Foundation assembles talented young graduate researchers from around the world each year, offering them the chance to further their careers in the molecular biology of aging and longevity by performing cutting-edge research at the Foundation's research center, or in allied laboratories also focused on aging. We are all still aging today, and the researchers who lead the deployment of the first generation of clinical rejuvenation treatments will not be those presently at the peak of their careers. Creating the next generation of the research community is just as important as persuading the present generation to focus on repair-based approaches to treating aging.
Still, much can be accomplished with comparatively little nowadays. The state of biotechnology today is very different from that of even just ten or twenty years ago: tasks that would have required a fully staffed institution and tens of millions of dollars - if they were even possible at all - can now be achieved by a single researcher and tens of thousands of dollars. The cost of life science research is plummeting, even as the capabilities of laboratory technologies expand just as rapidly.
The SENS Research Foundation has been showing off the work of the 2013 interns over the past few months:
- A Spotlight on SENS Research Foundation Interns
- Another Spotlight on SENS Research Foundation Interns
Here is the latest installment of posts:
Chronic obstructive pulmonary disease (COPD) is a lung disease which is currently the 4th leading cause of death in the world, affecting the lives of hundreds of millions every year. In this disease, an excessive inflammatory response to noxious particles or gases causes airflow to become restricted. A deadly combination of chronic inflammation in the small airways and destruction of the alveoli slowly limits the lungs' ability to do their job transmitting oxygen to the blood.
The two main risk factors for COPD are smoking and age. Senescence of cells in the airway due to environmental stress, such as smoking, or due to advanced age may explain these risk factors. Senescence is a non-proliferative state which a normal, dividing cell may enter to prevent excessive cell growth. Although the senescent response limits tumorigenesis in these cells, it may also contribute to the pathogenesis of COPD by both limiting the proliferative capacity necessary for tissue repair and by promoting chronic inflammation.
To determine if senescence plays a role in COPD, I studied transgenic mice that possessed lung cells with an impaired ability to undergo senescence. The senescence-impaired cells are a special type of epithelial cell found in small airways in the lungs, called Clara cells. By inactivating the tumor suppressor gene p53 in these cells, one of the main regulatory pathways of cellular senescence was impaired. I also developed a protocol for inducing COPD-like symptoms by treating the mice with aerosolized lipopolysaccharide (LPS). This allowed me to compare the response of these transgenic mice to normal mice when faced with COPD-inducing conditions. The correlation between fewer senescent cells and lower levels of inflammation suggests that the senescence of Clara cells indeed might play an important role in the pathogenesis of COPD. Further study of the role senescence plays in the pathogenesis of COPD could reveal new targets for COPD therapies.
Cellular senescence is a process in which a cell ceases to proliferate in response to oncogenic stimuli. Ironically, although senescence helps protect the cell in question from becoming cancerous, the senescence-associated secretory phenotype (SASP) has been shown to contribute to age-related diseases, in particular cancer. The Campisi lab has previously demonstrated that several proteins involved in the DNA damage response (DDR) pathway are also necessary for the SASP. Inhibition of histone deacetylases (HDACs) and activation of the ataxia telangiectasia mutated (ATM) protein in turn activate the SASP. This suggests that the state of the chromatin rather than the physical breaks in DNA is responsible for initiating the SASP response in senescent cells. My project sought to characterize the role specific HDACs play in ATM activation and SASP induction.
Previous research in Dr. Anderson's laboratory revealed that lithium, a drug commonly used to treat bipolar disorder, also may prevent neurodegeneration in an animal model of Parkinson's disease. Working with postdoctoral researcher Dr. Christopher Lieu, I tried to determine what molecular pathway is associated with the previously observed effects of lithium on the symptoms of a Parkinson's disease animal model.
Two possible mechanisms were investigated: autophagy (the process by which a cell can recycle and remove metabolic cellular debris, protein aggregates, and damaged organelles) and inflammation. One theory argues that dysfunction in the neurocellular autophagy pathway is responsible for the neuronal degeneration and resulting loss of motor control observed in Parkinson's disease. If so, reactivation of the autophagy mechanism may be responsible for the neuroprotective properties of lithium in a Parkinson's disease model. We also tested the possibility that the neuroprotective properties of lithium may be a result of lithium's effect on neuronal inflammation.
Actin fibers are a key component of the proteolytic invadopodia used by breast cancer cells during metastasis. A formin protein known as FMNL1 plays a crucial role in actin assembly during macrophage migration and has been implicated in proteolytic invadopodia as well. My summer project tested whether or not inhibition of FMNL1 function in breast cancer cells [would] limit their metastatic capabilities.
I attempted to lower FMNL1 protein levels [in] cells by using a process known as RNA interference (RNAi), a technique that can be used to selectively remove a specific RNA transcript from cells. Once I confirmed that FMNL1 protein levels were reduced, I tested the invasive capability of the cells. RNAi-treated cells were placed on an artificial basement membrane, and I measured the number of cells that were able to move through the membrane. Fewer FMNL1 siRNA-treated cells were able to penetrate the membrane compared to cells treated with a control siRNA construct.