Progress Against Aging beta
ShareTo determine what progress is being made against aging (reversing aging rather than merely slowing it down; please see the "Aging and How to Defeat It" page for further details), it is necessary to track two initiatives—the Mprize and SENS—that promise to accelerate progress against aging with the goal of eventually defeating aging. The Mprize's money pot must grow in order for it to continue encouraging scientists to create ever long-lived mice using interventions that could be adapted to work at defeating aging in people. The larger the Mprize becomes, the more effective it will be at creating competition among scientists. SENS is a set of medical therapies that have been proposed to entirely defeat aging in people. Each of these therapies is composed of multiple projects which are in different stages of development.
The Mprize
The Methuselah Foundation's Mprize is a competition that encourages scientists to compete in creating ever long-lived mice. The Mprize consists of the following separate prize competitions:
- the Longevity Prize, awarded to the research team that breaks the world record for the oldest mouse using any kind of intervention, and
- the Rejuvenation Prize, awarded to the research team that breaks the world record for the greatest extension of lifespan in mice after only getting started with treatment when the mice are already late into their lives.
By seeking interventions that are initiated at a late age, the Rejuvenation Prize encourages scientific research that is most likely to benefit people that are alive today. The latest winner of the Rejuvenation Prize, Dr. Stephen Spindler of UC Riverside, used an intervention called calorie restriction to produce a group of mice that lived for an average of 1,356 days (3.7 years). Since interventions that merely slow aging such as calorie restriction will not be able to extend the lifespans of mice indefinitely, it will be necessary to employ other kinds of interventions that seek to reverse aging such as SENS in order to win future Rejuvenation Prizes.
Rejuvenation Prize Progress
In order for the Mprize to continue encouraging scientists to create long-lived mice using interventions that could be adapted to work for people, the amount of prize money must increase as quickly as possible and become as large as possible. Since the Methuselah Foundation is a non-profit charity, it depends on donations to fund the Mprize. The following table displays the Rejuvenation Prize's winners and yearly funding progress:
| Year | Funding Progress | Rejuvenation Prize Winners | Average Mouse Lifespan | Intervention |
|---|---|---|---|---|
| 2004 | $54,000* | Dr. Stephen Spindler of UC Riverside | 1,356 days (3.7 years) | Calorie restriction |
| 2005 | $1.3 million* | None | N/A | N/A |
| 2006 | $1.4 million* | None | N/A | N/A |
| 2007 | $1.5 million* | None | N/A | N/A |
| 2008 | N/A | None | N/A | N/A |
| 2009 | $1.6 million* | None | N/A | N/A |
| Present | $3.3 million | None | N/A | N/A |
*From 2004 to 2009, it is unclear how much of the donations labeled "Commitments Outstanding" or "Other Commitments" on the Methuselah Foundation's "Funding" page were applied to its Rejuvenation Prize fund, and therefore, the listed funding figures only reflect minimum totals.
SENS Therapies and Projects
Currently, SENS is comprised of seven major types of medical therapies addressing seven major categories of aging damage. The following sections contain a list of projects for each of the seven major types of SENS therapies. For a more detailed explanation of how aging, aging damage, age-related disease, and SENS are related, please see the "Aging and How to Defeat It" page.
Except for most AmyloSENS and RepleniSENS projects, the non-profit SENS Foundation is largely responsible for progress in all of the other kinds of SENS projects and depends on donations to fund those projects.
SENS Project Stages
The following table displays the stages that every SENS project must go through before it can be approved for human use and the kind and number of SENS projects in each stage. Please note that this list of SENS projects is currently incomplete; more AmyloSENS and RepleniSENS projects and more complete background information for all other projects will be added in the near future.
| Project Stage | SENS Projects | Total Projects (14) |
|---|---|---|
| Planned: Stage 1 of 7 Scientific research planned to be conducted to develop a therapy |
GlycoSENS: Enzymes to Break Glucosepane Cross-Links |
1 |
| Discovery: Stage 2 of 7 Scientific research conducted to develop a therapy |
AmyloSENS: Vaccine for Transthyretin Amyloid |
7 |
| Preclinical: Stage 3 of 7 Laboratory tests and animal studies to demonstrate the safety and efficacy of a therapy |
ApoptoSENS: Filtering Procedure to Clear Aged T Cells LysoSENS: Enzymes to Degrade A2E LysoSENS: Laser Light to Degrade Lipofuscin MitoSENS: Efficient, Allotopic Expression of All mtDNA |
4 |
| Phase I: Stage 4 of 7 Clinical studies in patients to demonstrate the safety of a therapy |
None | 0 |
| Phase II: Stage 5 of 7 Clinical studies in patients to demonstrate the preliminary efficacy and gather more evidence of the safety of a therapy |
OncoSENS: Innate Immunotherapy Against Cancer (Clinical Trial 08001-BMSCTI) | 1 |
| Phase III: Stage 6 of 7 Large-scale clinical studies in patients to provide proof of the efficacy and safety of a therapy |
AmyloSENS: Vaccine for Beta-Amyloid |
1 |
| Approved: Stage 7 of 7 A regulatory agency approves the therapy for patient use |
None | 0 |
Details of SENS Projects
This section displays the details of every project and project component of each SENS therapy.
AmyloSENS
| SENS Therapy | Aging Damage | Age-Related Disease |
|---|---|---|
| AmyloSENS: Clearing junk outside cells This kind of therapy aims to clear the protein junk, amyloid, that accumulates outside cells. This could be accomplished by using a vaccine to stimulate the immune system to digest this junk. |
Junk outside cells This kind of damage consists of the protein junk, amyloid, that accumulates outside cells and serves no useful biological purpose. The most well-known protein junk of this kind, beta-amyloid, is thought to be responsible for the development of Alzheimer's disease. |
Alzheimer's disease Diabetes, type II Heart disease Stroke |
| Vaccine for Beta-Amyloid | |
|---|---|
| SENS Therapy AmyloSENS: Clearing junk outside cells Aging Damage Junk outside cells Age-Related Disease Alzheimer's disease Organization Elan Corporation Wyeth (Pfizer) Project Stage Phase III: Stage 6 of 7 |
Project Description This project seeks to develop an antibody-based (bapineuzumab) vaccine to stimulate the immune system in clearing beta-amyloid which is thought to be responsible for Alzheimer's disease. Phase II Results
2005/04: First Phase II clinical study begins 2006/10: First Phase I clinical study begins 2007/12: First Phase III clinical studies begin 2010-2014: Several Phase II and Phase III clinical studies are due to be completed Resources Alzheimer Research Forum - Bapineuzumab ClinicalTrials.gov - Search results for bapineuzumab SENS Foundation - AmyloSENS |
| Vaccine for Transthyretin Amyloid | |
|---|---|
| SENS Therapy AmyloSENS: Clearing junk outside cells Aging Damage Junk outside cells Age-Related Disease Heart disease Organization SENS Foundation Project Stage Discovery: Stage 2 of 7 |
Project Description |
A larger list of AmyloSENS projects is forthcoming.
ApoptoSENS
| SENS Therapy | Aging Damage | Age-Related Disease |
|---|---|---|
| ApoptoSENS: Elimination of death-resistant cells This kind of therapy aims to get rid of death-resistant cells. This could be accomplished by injecting substances that kill only the problem cells, using genetic engineering to cause unwanted cells to self-destruct, or stimulating the immune system to destroy the target cells. |
Death-resistant cells This kind of damage consists of the accumulation of cells that do not die when they are supposed to and damage neighboring, healthy cells by secreting harmful substances. Some death-resistant fat cells promote type II diabetes, other death-resistant cells promote the progression of cancer, and death-resistant immune cells impair the healthy functioning of the immune system. |
Cancer Diabetes, type II Heart disease (suspected) Immune system dysfunction Osteoporosis (suspected) |
| Filtering Procedure to Clear Aged T Cells | |
|---|---|
| SENS Therapy ApoptoSENS: Elimination of death-resistant cells Aging Damage Death-resistant cells Age-Related Disease Immune system dysfunction Organization SENS Foundation Project Stage Preclinical: Stage 3 of 7 |
Project Description
2008: A procedure for clearing aged, immune system T cells begins to be developed 2009: A procedure, nicknamed "scrubbing," that cleared T cells from the blood of mice is developed Resources SENS Foundation - ApoptoSENS SENS Foundation - Senescent T-cell scrubber
|
| ? to Clear Aged T Cells | |
|---|---|
| SENS Therapy ApoptoSENS: Elimination of death-resistant cells Aging Damage Death-resistant cells Age-Related Disease Immune system dysfunction Organization SENS Foundation Project Stage Discovery: Stage 2 of 7 |
Project Description This project seeks to develop a ? procedure for clearing aged, immune system T cells, a major cause of immune system dysfunction. 200?: Project planning begins 200?: A research collaboration with Dr. Megan Smithey working in the lab of Dr. Janko Nikolich-Zugich at the University of Arizona begins Resources SENS Foundation - ApoptoSENS SENS Foundation - Rejuvenating the immune system |
GlycoSENS
| SENS Therapy | Aging Damage | Age-Related Disease |
|---|---|---|
| GlycoSENS: Breaking protein cross-links This kind of therapy aims to break protein cross-links. This could be accomplished by developing specially-designed, cross link-breaking drugs, enzymes, or proteins. |
Tissue stiffening This kind of damage consists of structural proteins outside of cells that stick together ("cross-link") instead of easily moving past each other to provide flexible support for such tissues as artery walls, eye lenses, and ligaments. These cross-linked proteins stiffen tissues like the artery wall leading to high blood pressure. |
Arthritis Atherosclerosis Cataracts Diabetes, type II Heart disease Kidney disease Skin aging |
| Enzymes to Break Glucosepane Cross-Links | |
|---|---|
| SENS Therapy GlycoSENS: Breaking protein cross-links Aging Damage Tissue stiffening Age-Related Disease Arthritis Atherosclerosis Cataracts Heart disease Kidney disease Skin aging Organization SENS Foundation Project Stage Planned: Stage 1 of 7 |
Project Description This project seeks to develop enzymes capable of breaking the ubiquitous glucosepane cross-links which may comprise as much as 98 percent of all long-lived cross-links and are associated with many age-related diseases. Resources SENS Foundation - GlycoSENS |
LysoSENS
| SENS Therapy | Aging Damage | Age-Related Disease |
|---|---|---|
| LysoSENS: Clearing junk inside cells This kind of therapy aims to clear junk that accumulates inside cells. This could be accomplished by equipping the lysosome with new enzymes taken from soil bacteria that are capable of degrading this junk. |
Junk inside cells This kind of damage consists of various kinds of junk that accumulate inside certain types of cells and cannot be broken down by the lysosome, the cell's most powerful garbage disposal machinery. This junk eventually fills up the cell making it dysfunctional or even killing it. |
Alzheimer's disease Atherosclerosis Macular degeneration Parkinson's disease Skin aging |
| Enzymes to Degrade A2E | |
|---|---|
| SENS Therapy LysoSENS: Clearing junk inside cells Aging Damage Junk inside cells Age-Related Disease Alzheimer's disease Atherosclerosis Organization SENS Foundation Project Stage Preclinical: Stage 3 of 7 |
Project Description This project seeks to develop enzymes that can degrade A2E, a type of junk that accumulates inside cells and is responsible for age-related macular degeneration. 200?: Project planning begins SENS Foundation - Degradation of A2E SENS Foundation - LysoSENS |
| Degradation of Lipofuscin | |
|---|---|
| SENS Therapy LysoSENS: Clearing junk inside cells Aging Damage Junk inside cells Age-Related Disease Alzheimer's disease Macular degeneration Parkinson's disease Skin aging |
Project Description This project seeks to determine whether laser light can degrade lipofuscin, a general term for many kinds of junk that accumulates inside cells. Resources SENS Foundation - LysoSENS |
| Organization Immortality Institute SENS Foundation Project Stage Preclinical: Stage 3 of 7 |
Laser Light to Degrade Lipofuscin This project seeks to determine whether laser light can degrade lipofuscin, a general term for many kinds of junk that accumulates inside cells. Preclinical Results
2009/10: Worms start to be treated with different amounts of laser light 2010/01: Despite some environmental contamination of the experiment, there seems to be some benefit with the most heavily laser-treated group of worms, and replication with more redundancy and better control over environmental conditions is recommended. Resources Immortality Institute - Laser Ablation of Lipofuscin Nason Schooler's Research Blog SENS Foundation - Laser ablation of lipofuscin |
| Organization SENS Foundation Project Stage |
Enzymes to Degrade Lipofuscin This project seeks to determine whether laser light can degrade lipofuscin, a general term for many kinds of junk that accumulates inside cells. Preclinical Results
2009/10: Worms start to be treated with different amounts of laser light 2010/01: Despite some environmental contamination of the experiment, there seems to be some benefit with the most heavily laser-treated group of worms, and replication with more redundancy and better control over environmental conditions is recommended. Resources Immortality Institute - Laser Ablation of Lipofuscin Nason Schooler's Research Blog SENS Foundation - Laser ablation of lipofuscin |
| Enzymes to Degrade 7KC | |
|---|---|
| SENS Therapy LysoSENS: Clearing junk inside cells Aging Damage Junk inside cells Age-Related Disease Alzheimer's disease Atherosclerosis Organization SENS Foundation Project Stage Discovery: Stage 2 of 7 |
Project Description This project seeks to develop enzymes that can degrade 7KC (7-ketocholesterol), a type of junk that accumulates inside cells and is implicated as a major cause of atherosclerosis and also involved in Alzheimer's disease. 200?: Project planning begins SENS Foundation - Degradation of 7KC SENS Foundation - LysoSENS |
MitoSENS
| SENS Therapy | Aging Damage | Age-Related Disease |
|---|---|---|
| MitoSENS: Mitigation of mitochondrial mutations This kind of therapy aims to mitigate mitochondrial mutations. This could be accomplished by copying the mitochondrion's 13 protein-encoding genes into the cell's better-protected nucleus where most mitochondrial DNA resides anyway, repairing or replacing the mitochondrion's mutated genes, or preventing cells with mutant mitochondria from spreading free radicals to the rest of the body. |
Mutations in the cell's mitochondria This kind of damage consists of the accumulation of mutations in the 13 protein-encoding genes of mitochondria, the power plants of the cell, that—although present in a relatively small number (about 1%) of cells—generate free radical damage that spreads throughout the entire body. This free radical damage may lead to increased frailty. |
Specific diseases unknown (but causes body-wide, free radical damage that may lead to increased frailty) |
| Efficient, Allotopic Expression of All mtDNA, Copying the Mitochondrion's 13 Protein-Encoding Genes into the Cell's Nucleus, or Efficient, Allotopic Expression of mtDNA and Protein Import into Mitochondira |
|
|---|---|
| SENS Therapy MitoSENS: Mitigation of mitochondrial mutations Aging Damage Mutations in the cell's mitochondria Age-Related Disease Specific diseases unknown Organization SENS Foundation Project Stage Preclinical: Stage 3 of 7 |
Project Description This project seeks to mitigate mitochondrial mutations by copying the mitochondrion's 13 protein-encoding genes into the cell's better-protected nucleus where most mitochondrial DNA resides anyway. 2006: Preliminary work is performed by Dr. Ian Holt at Cambridge University 2007: Extension of preliminary work is performed by Mark Hamalainen in the lab of Dr. Ian Holt at Cambridge University Resources SENS Foundation - MitoSENS |
| Project Component: Efficient, Allotopic Expression of mtDNA This project component seeks to demonstrate efficient expression of mitochondrial DNA (mtDNA) copied into the cell's nucleus (allotopic expression). 200?: Project component planning begins 2008: Efficient, allotopic expression in cultured human fibroblasts carrying mtDNA mutations has been demonstrated by Mark Hamalainen at the lab of Dr. Marisol Corral-Debrinski at Institut de la Vision Paris 2009-Present: Allotopic expression in the eyes of rats is being assessed at the lab of Dr. Marisol Corral-Debrinski at Institut de la Vision Paris |
|
| Project Component: Efficiency of Transgenic Protein Incorporation into Mitochondria This project component seeks to further validate results of the expression of mitochondrial DNA (mtDNA) in the cell's nucleus by examining the efficiency in which the proteins created using mtDNA in the cell nucleus (transgenic) are incorporated into mitochondria using a technique called 2D Blue-Native PAGE. 200?: Project component planning begins Future: This research will be performed in collaboration with the lab of Dr. Marisol Corral-Debrinski at Institut de la Vision Paris. |
|
| Project Component: Co-expression of Multiple, Allotopically-Expressed mtDNA Genes This project component seeks to investigate the co-expression of multiple, mitochondrial (mtDNA) genes expressed in the cell's nucleus (allotopic expression) including a version of yeast NDI1 optimized for humans and/or mice. 200?: Project component planning begins Future: This research will be performed in collaboration with the lab of Dr. Marisol Corral-Debrinski at Institut de la Vision Paris. |
|
OncoSENS
| SENS Therapy | Aging Damage | Age-Related Disease |
|---|---|---|
| OncoSENS: Development of cancer cures This kind of therapy—the most difficult to develop in the fight against aging—would rely on true cures for cancer. Several, potentially-revolutionary approaches exist—from the use of the body's own immune system to kill cancer to the removal of telomeres which cancer depends on to grow. |
Mutations in the cell's nucleus This kind of damage consists of mutations in the genes of the cell's nucleus. While most mutations are not very harmful, some mutations lead to cancer. |
Cancer |
| Innate Immunotherapy Against Cancer | |
|---|---|
| SENS Therapy OncoSENS: Development of cancer cures Aging Damage Mutations in the cell's nucleus Age-Related Disease Cancer |
Project Description This project seeks to cure cancer by developing therapies based on the innate cancer immunity which some people seem to possess. Current adaptive immunity approaches rely on training the immune system to kill cancer but have yet to deliver on much of their promise. This may be because adaptive immunity is just too clever for its own good; perhaps cancer uses adaptive immunity's own high adaptability to always find a way to fool it. Instead of focusing on adaptive immunity approaches, this project seeks to use the more "stubborn" white blood cells (neutrophil granulocytes) of innate immunity to potentially circumvent the problems that have plagued the adaptive immunity approaches. Besides WILT, this approach to curing cancer is the most promising of any being developed today. 1999: A single male mouse that unexpectedly survived challenges of lethal cancer cell injections is noticed by Dr. Zheng Cui in his lab at Wake Forest University School of Medicine 2003/04: Results published by Dr. Zheng Cui demonstrated spontaneous cancer regression and complete cancer resistance in a unique strain of lab mouse due to its cancer-killing granulocytes 2006/05: Results published by Dr. Zheng Cui demonstrated the ability to cure cancer in normal mice by transferring granulocytes from the cancer-resistant mice Resources Livly - Cancer Research WFUSM - Spontaneous Regression of Advanced Cancer in Mice |
| Organization South Florida Bone Marrow/Stem Cell Transplant Institute Life Extension Foundation Project Stage Phase II: Stage 5 of 7 |
Innate Immunotherapy Against Cancer (Clinical Trial 08001-BMSCTI) This Phase I/II clinical trial seeks to determine whether white blood cell (granulocyte) infusions from healthy, unrelated donors can be used to treat cancer. It is designed to accommodate 29 patients, costs a total of $4 million, and is being conducted by Dr. Dipnarine Maharaj at the South Florida Bone Marrow/Stem Cell Transplant Institute. 2009/04: Clinical trial begins with just 4 patients due to lack of funding 2009/10: Paperwork starts for a $2 million grant from the National Institutes of Health which—if approved—will take at least one year to be awarded 2009/11: Clinical trial takes on a fifth patient Resources ClinicalTrials.gov - 08001-BMSCTI Florida Atlantic University - Funding a cure South Florida Bone Marrow/Stem Cell Transplant Institute |
| Organization Livly Project Stage Discovery: Stage 2 of 7 |
Innate Immunotherapy Against Cancer (Livly's Research) Livly, a non-profit corporation, seeks to identify people that have granulocytes with exceptional cancer-killing ability and also identify drugs and other interventions that boost the cancer-killing ability of granulocytes in order to develop innate immune cell-based cancer therapies. Current Results
2009/06: Cancer-killing ability of human granulocytes confirmed by time-lapse video microscopy 2009/06: Preliminary, in vitro testing confirms that the cancer-killing ability of granulocytes differs among from different people but granulocytes do not seem to kill that many cancer cells 2009/08: In vitro testing indicates that the most potent human granulocytes found so far kill just 5% of cancer cells 20??/??-Present: A test is being developed to screen a large number of drugs and other interventions for their ability to improve granulocytes' cancer-killing ability 2009/12-Present: Livly partners with the Direct Oncology Foundation to raise $100,000 to sequence cancer resistant mice at Wake Forest University Resources Livly - Cancer Research |
| WILT (Whole-body Interdiction of Lengthening of Telomeres) | |
|---|---|
| SENS Therapy OncoSENS: Development of cancer cures Aging Damage Mutations in the cell's nucleus Age-Related Disease Cancer Organization SENS Foundation Project Stage Discovery: Stage 2 of 7 |
Project Description This project seeks to cure cancer by removing the genes needed to maintain the telomere-lengthening machinery of all cells in the body thus making it impossible for cancer to grow. Since dividing cells that lack telomeres will eventually stop growing after about a decade, the periodic reseeding of tissues using stem cells will be needed to maintain healthy tissues. While WILT might appear to be too ambitious, it is meant to be a treatment-of-last-resort in case other potential cancer cures fail to work. Resources SENS Foundation - OncoSENS |
| Project Component: Characterization of the ALT Enzyme This project component seeks to characterize the enzyme responsible for alternative lengthening of telomeres (ALT) which along with telomerase is responsible for maintaining a cell's telomeres without which cancer cannot grow. Recent observations indicate a previously unsuspected gene for ALT, and a relatively simple series of experiments could test these observations. 200?: Project component planning begins 200?: A preliminary search for ALT genes is performed by Matthias Bollmann at Gymnasium Carolinum |
|
| Project Component: Role of Telomerase Activity in the Stem Cell Niche This project component seeks to determine whether telomerase activity—independent of telomere length—has a role in maintaining the health of stem cells or their rarely-dividing neighbors in the so-called "stem cell niche." This research will be . 200?: Project component planning begins 200?-Present: This project component has begun with research in the blood of mice at the lab of Dr. Zhenyu Ju at Chinese Academy of Medical Sciences |
|
| Project Component: Significance of Non-Cancer-Causing Mutations in a Normal Lifetime This project seeks to determine the significance of non-cancer-causing mutations in the cell's nuclear DNA within a normal lifetime. 200?: Project component planning begins 200?-Present: This project component has begun at the lab of Dr. Jan Vijg at Albert Einstein College of Medicine |
|
RepleniSENS
| SENS Therapy | Aging Damage | Age-Related Disease |
|---|---|---|
| RepleniSENS: Stem cells and tissue engineering This kind of therapy aims to replace lost cells and organs that are damaged beyond repair. This could be accomplished by injecting stem cells into tissues and replacing entire organs with ones grown outside the body using tissue engineering techniques. |
Cell loss This kind of damage consists of the loss of cells in different tissues of the body such as the brain, heart, and skeletal muscle. This cell loss eventually leads to tissue and organ dysfunction. Tissue stiffening This kind of damage consists of structural proteins outside of cells that stick together ("cross-link") instead of easily moving past each other to provide flexible support for such tissues as artery walls, eye lenses, and ligaments. These cross-linked proteins stiffen tissues like the artery wall leading to high blood pressure. |
Alzheimer's disease Arthritis Atherosclerosis Heart disease Immune system dysfunction Muscle atrophy Parkinson's disease Skin aging |
| Reversal of Thymic Involution Using Growth Factors | |
|---|---|
| SENS Therapy RepleniSENS: Stem cells and tissue engineering Aging Damage Cell loss Age-Related Disease Immune system dysfunction Organization SENS Foundation Project Stage Discovery: Stage 2 of 7 |
Project Description This project seeks to reverse the shrinkage of the thymus (thymic involution), a major cause of immune system dysfunction, using growth factors. 200?: Project planning begins 200?: A research collaboration with Dr. Megan Smithey working in the lab of Dr. Janko Nikolich-Zugich at the University of Arizona begins Resources SENS Foundation - RepleniSENS SENS Foundation - Rejuvenating the immune system |
A larger list of RepleniSENS projects is forthcoming.
Acknowledgement
This page has been developed and is being maintained in cooperation with the SENS Foundation.