Funding a Cure for Aging

In order to accelerate the access to healthy longevity for all of us we directly fund cutting-edge research on molecular and cellular repair to combat the root causes of aging, support the creation of startups turning that research into rejuvenation therapies for human application and host an annual conference to support the amazing scientific community working in the field.

Internet Entrepreneur Michael Greve commits $10 million to SENS-related research and startups (sens.org)


     

     

The Undoing Aging Conference

To accelerate the development of actual rejuvenation therapies for human use, we have teamed up with SENS Research Foundation and created the annual Undoing Aging Conference in Berlin.

Undoing Aging is focused on the molecular and cellular of repair of age-related damage as the basis of therapies to bring aging under full medical control.

The conference has two main goals: support the remarkable scientific community already working on repair of age-related damage and create a unique opportunity for the broader scientific world to experience that the possibility of bringing aging under genuine medical control is achievable and, indeed, beginning to happen.

Speakers at Undoing Aging include leading researchers from around the world focused on topics including stem cells, senescent cells, immunotherapies, biomarkers and drug discovery.

Undoing Aging 2019 takes place March, 28 - 30 in Berlin.

 

 undoing-aging.org

  

 

 

Supported Research Projects

 

     

   

Forever Healthy Fellowship in Rejuvenation Biotechnology

In order to get more young scientist joining the quest to get aging under full medical control, we have created the Forever Healthy Fellowship in Rejuvenation Biotechnology.

The fellowship is open to Ph.D.'s (or equivalent degree) with project proposals that clearly identify the form of cellular and molecular aging damage to be targeted and will describe the strategy to be advanced towards its direct detection, removal, or repair and significant translational potential.

For selected candidates, the fellowship covers support for a three-year project, to be carried out at the SENS Research Center in Mountain View, California. It includes salary for the fellow, benefits, supplies, and space in our fully equipped research lab. Nearby universities available for collaboration include Stanford, UCSF, UC Berkeley, The Buck Institute for Research on Aging, and UC Santa Cruz.

 

More Info ...

  

  

     

   

Allotopic expression of mitochondrial genes

The accumulation of dysfunctional mitochondria with severe mutations in their mitochondrial DNA is a significant consequence of aging and is implicated in age-related diseases as well as in several currently incurable inherited mitochondrial disorders.

The SENS Research Foundations Mitochondria Group’s primary goal is to find ways to rescue mutations in mitochondrial DNA. Their main approach is to re-engineer mitochondrial genes and place them in the nucleus.

The team has had phenomenal success in rescuing cells derived from a patient by expressing two re-engineered genes simultaneously and have recently published this work, which covers the mitochondrial genes ATP6 and ATP8, in Nucleic Acids Research.

 

SENS Research Foundation, Dr. Matthew O’Connor

  

  

   

   

Removal of tangled tau proteins

The formation of tau tangles is suspected to be a major contributor to the progression of neurodegenerative diseases. The project will explore the elimination of these age-related waste products in brain cells, using the same approach that SENS Research Foundation has applied in its atherosclerosis and macular degeneration research projects in recent years. The ultimate goal is to find treatments for Alzheimer's and Parkinson's disease.

 

The Buck Institute for Research on Aging, Prof. Julie K. Andersen

   

  


   
   

   

Basic research on glucosepane crosslinks

Advanced glycation end-products (AGEs) comprise a class of modifications of proteins formed from chemical reactions between sugars and proteins. AGEs are generated during our aging process, and their excessive formation is implicated in conditions such as diabetes and cardiovascular disease and has been shown to induce inflammation, oxidative stress, and other pathological effects. It is hypothesized that disrupting AGE crosslinks can reverse degenerative effects in tissue.

To test this hypothesis, AGEs have been synthesized, including glucosepane, pentosinane, and methylglyoxal-derived hydroimidazolone. With these synthesized constructs, the Yale team is developing reagents to characterize the chemical properties of AGEs and study their interactions with proteins in cellular and tissue systems.

These assays reproduce the situation in the body and act as guides in the development of therapeutics that can inhibit or prevent the formation of AGEs, and thereby reverse the pathology associated with the human aging process.

 

Yale University, Dr. David Spiegel

 

  

   
   

   
   

Development of monoclonal antibodies against glucosepane

Glucosepane is the most prevalent crosslink found in collagen in people over 65 years of age. It has been strongly correlated to age-related tissue damage through various mechanisms. 

In addition to their basic research on crosslinks, the team at the Spiegel lab is now utilizing their novel synthetic glucosepane derivatives to develop the first monoclonal anti-glucosepane antibodies.

Access to these antibodies would provide discrete, specific reagents for labeling, studying, and perhaps also cleaving glucosepane in vivo. Such tools have tremendous potential to reverse age-related damage as it occurs in human tissues.

 

Yale University, Dr. David Spiegel

 

  

   

   

   

Increased safety of gene therapies

Many potential treatments of age-related diseases require the addition of new genes to the genome of cells in the body, a technology known as somatic gene therapy. The technology has been hampered, up until now, by the inability to control where the gene is inserted.

That lack of control resulted in a significant risk of insertion in a location that encourages the cell to become malignant. The SENS Research Foundation has devised a new method for inserting genes into a pre-defined location. In this program, this will be done as a two-step process, in which first CRISPR is used to create a "landing pad" for the gene, and then the gene is inserted using an enzyme that only recognizes the landing pad.

The SENS Research Foundation has created “maximally modifiable mice” that already have the landing pad, and this project will evaluate how well the insertion step works in different tissues.

 

 SENS Reasearch Foundation &

The Buck Institute for Research on Aging, Dr. Brian Kennedy

   

  

   

   

Search for unknown, high-abundance tissue crosslinks 

Arteries slowly stiffen with age, in substantial part because of adventitious cross-linking of the structural proteins collagen and elastin. Developing rejuvenation biotechnologies to break these crosslinks is key to restoring youthful arterial function. However, it is vital that we understand which crosslinks do the most damage to our cellular structure.

Dr. Clark has established analytical methods required to study extracellular tissues and obtain preliminary data on the aging of tissues in mice. Preliminary data has allowed the methods to be tested and to explore where the analytical focus should be in future studies and method developments.

The entire process from tissue isolation through to the final analytical methods has been observed, demonstrating that the team has produced a solid set of analytical methods and that we are one step closer to understanding the role of cross-linking within our arteries.


The Babraham Institute, Dr. Jonathan Clark

 

  

   

   

Removal of cells secreting toxic factors

When our cells detect that they may become cancerous or contribute to other forms of abnormal growth, they trigger machinery that stops them from growing to pre-empt the risk. These non-dividing “senescent” cells develop resistance to signals for apoptosis (programmed cell death) and secrete inflammatory signaling molecules and protein-degrading enzymes into their local environment. This latter phenomenon, which is thought to contribute to inflammatory and disease-promoting processes in aging, is called the senescence-associated secretory phenotype, or SASP.

The Buck senescent cell team has achieved some promising results via experiments with a natural compound called apigenin, which appears to both interrupt the SASP and potentially ablate senescent cells themselves.

 

The Buck Institute for Research on Aging, Dr. Judy Campisi

   

  

   

   

Removal of senescent immune cells

Various types of unwanted cells accumulate during aging and affect the function of many systems, including the immune system. Some of these cells are cleared by the immune system itself, but some are not, possibly leading to a vicious cycle of decline. The project explores techniques for eliminating these cells and rejuvenating the immune system by forcing the unwanted immune cells to “commit suicide", and/or by augmenting the cell-killing function of healthy immune cells and thus augmenting the aging immune system’s defenses against senescent cells.

 

The Buck Institute for Research on Aging, Dr. Judy Campisi

   

  

   

   

Student Education

SRF’s educational efforts provide support for aspiring young scientists from their elementary school studies through their postdoctoral training. Since its inception three years ago, SRF Education has supported undergraduate research efforts primarily through its Summer Scholars and Literature Review Programs.

This year, SRF is launching programs to begin supporting postgraduate training of rejuvenation biotechnology researchers. Through a partnership with the University of Oxford and the Harvard Stem Cell Institute, SRF has started supporting training of graduate students interested in pursuing a career in rejuvenation biotechnology.

Also this year, the Literature Review Program will transition into a remote, non-bench research program. Student volunteers will have the opportunity to participate in research studying obstacles blocking or slowing the development of therapeutics as well as research scrutinizing possible solutions to remove or mitigate those problems. These new project offerings will be developed in collaboration with the University of Oxford and the Centre for the Advancement of Sustainable Medical Innovation.

 

SENS Research Foundation, Dr. Gregory Chin

  

 

 

Supported Startups

 

   

   

Oisin Biotechnologies

When a cell reaches it's end of life or becomes damaged beyond repair, it is supposed to either kill itself or signal the immune system to remove it. Unfortunately, every so often this mechanism fails, the cell stays around indefinitely and starts poisoning its environment. Over time we accumulate more and more of these harmful, death-resistant senescent cells.

A recent study in rodents has shown that clearing senescent cells can both reduce the adverse effects of age-related diseases and extend the healthy lifespan by up to 35%.

Oisin is developing a cellular repair therapy based on a genetically-targeted intervention to clear senescent cells from our body.

 

oisinbio.com

 

   

   

LysoClear

Age-related macular degeneration (AMD) is the leading cause of vision loss among people over the age of 50.

AMD is thought to be caused by aggregation of A2E a toxic, non-degradable cellular waste product in our eye's retina cells.

Lysoclear is a molecular repair therapy based on the targeted delivery of exogenous A2E degrading enzymes to our retina cells to eliminate A2E, treat AMD and restore vision.

The team recently announced a Series-A offering to bring its product through Phase I clinical trials. LysoClear would be the first clinical candidate based on the repair and rejuvenation paradigm, pioneered by the SENS research foundation.


lysoclear.com

 

   

   

CellAge

CellAge is aiming to increase human healthspan and reduce the incidence of age-related diseases by helping the human body destroy senescenct cells.

The team is focusing on a novel approach for this challenge by developing synthetic promoters for senescence cell detection and removal.

The joint expertise in senescence, synthetic biology and bioinformatics gives CellAge a unique angle on improving ways how gene therapies could be targeted to senescent cells.

 

cellage.org

 

   

   

AgeX

AgeX is applying technology relating to cell immortality and regenerative biology, to aging and age-related diseases. 

The company has three initial areas of product development: pluripotent stem cell-derived brown adipocytes; vascular progenitors; and induced Tissue Regeneration. Initial planned indications for these products are Type II diabetes, cardiac ischemia, and cancer respectively.

 

agexinc.com

 

   

   

Antoxerene

Antoxerene uses proprietary next generation screening technology to identify small molecule compounds to target pathways of aging.

The team focusses on next generation screens with higher predictive value than traditional approaches and expects first on-target therapeutic candidates for the p53/MDM2 pathway, a major oncology target, and the p53/FOXO4 pathway, a newly identified pathway involved in cellular aging.

 

antoxerene.com

 

   

   

Elevian

Elevian is a Harvard spinout developing therapeutics to stimulate regenerative capacity, the body’s ability to repair itself, which declines as we age. 

Elevian’s founders have identified circulating blood factors, including GDF11, which broadly stimulate regenerative capacity in aged animals across many organs and tissues (e.g. brain, heart, pancreas, muscle, and others).  Initially planned indications include Alzheimer’s Disease, heart failure, Type II diabetes, and age-related muscle dysfunction.

 

elevian.com

 

 

 

Past Projects

 

   

   

Fight Aging 2015 Fund-Raiser

In the last quarter of 2015, Fight Aging!, Josh Triplett, Christophe and Dominique Cornuejols, Stefan Richter and Michael Greve of Forever Healthy collaborated to create a $125,000 matching fund for SENS donations. From October 1st to December 31st, 2015 $1 donated to SENS rejuvenation research was matched with $1 from the fund. It was our challenge to the community: help us raise a total of $250,000 for research in a few short months.

These are critical years in the development of this field, a disruptive period of transition from the ineffective approaches of the past to a near future of far more effective means of treating aging. The greater the funding for early-stage research, the faster the progress towards treatments for aging.

 

Victory: $250,000 Raised for SENS Research (fight-aging.org)

 

   

   

Strategies to remove lipofuscin from aging cells

Many diseases of aging are driven in part by the accumulation of waste particular to specific cell types. For example, atherosclerotic lesions form when disabled, immobilized immune cells adhere in the arterial wall after taking in 7-ketocholesterol and other damaged cholesterol byproducts to protect the arterial wall from their toxicity. Alzheimer’s and Parkinson’s are also in part lysosomal diseases.

Many types of cells that rarely or never divide throughout adult life accumulate a more generic form of lysosomal waste known as lipofuscin, which impacts such critical cell types as neural, cardiac muscle, and skeletal muscle cells.

The team at Rice University investigates how to rapidly generate lipofuscin for quicker screening and researches small molecules that can both remove already present lipofuscin as well as native lipofuscin.

 

Rice University, Dr. Pedro Alvarez