Engineered negligible senescence
Encyclopedia
Strategies for Engineered Negligible Senescence (SENS) is the name Aubrey de Grey
gives to his proposal to research regenerative medical procedures to periodically repair all the age-related damage in the human body, thereby maintaining a youthful state indefinitely. The term first appeared in print in de Grey's 1999 book The Mitochondrial Free Radical Theory of Aging, and was later prefaced with the term "strategies" in the article Time to Talk SENS: Critiquing the Immutability of Human Aging De Grey argues for a "goal-directed rather than curiosity-driven" approach to the science of aging, and to this purpose he tentatively identifies seven "damages of aging" and their potential methods of treatments.
SENS has received media attention but has been criticized by some scientists. While many biogerontologists (scientists who study aging) find it "worthy of discussion" and SENS conferences feature important research in the field, some contend that de Grey's programme is too speculative given current scientific research, referring to it as "fantasy rather than science".
The goal of the Strategies for Engineered Negligible Senescence (SENS) is the complete reversal of all age-related illnesses and indefinite extension of the healthy human lifespan. The SENS project consists in implementing a series of periodic medical interventions designed to repair, prevent or render irrelevant all the types of molecular and cellular damage that cause age-related pathology and degeneration, in order to avoid debilitation and death from age-related causes.
De Grey defines aging as "the set of accumulated side effects from metabolism that eventually kills us", and, more specifically, as follows: "a collection of cumulative changes to the molecular
and cellular
structure of an adult
organism
, which result in essential metabolic
processes, but which also, once they progress far enough, increasingly disrupt metabolism, resulting in pathology
and death."
As de Grey states, "geriatrics
is the attempt to stop damage from causing pathology; traditional gerontology
is the attempt to stop metabolism
from causing damage; and the SENS (engineering) approach is to eliminate the damage periodically, so keeping its abundance below the level that causes any pathology." His approach to biomedical gerontology
("anti-aging medicine
") is thus distinctive because of its emphasis on rejuvenation
rather than attempting to slow the aging process.
He identifies what he believes to be the seven biological causes of senescence. According to de Grey, the causes of aging in humans are:
For each of these problems, de Grey outlines possible solutions, with a research and a clinical component. The clinical component is required because in some of the proposed therapies, feasibility has already been proven, but not completely applied and approved for use by human beings. He believes we will be able to apply these solutions before we completely understand the targeted aging mechanisms, which will take longer. He states that the goals work together to eliminate known causes of human senescence, are concrete, seem achievable, and are considered feasible by experts in the applicable fields. The goals were said to be taken from classical literature describing the biological causes of senescence.
De Grey proposes that engineered negligible senescence therapies could extend the human lifetime by many centuries or millennia, as early therapies give them enough time to seek more effective therapies later on. He describes an actuarial escape velocity of life extension
, when advances in senescence treatment come rapidly enough to save the lives of the oldest beneficiaries of the previous treatments.
(nDNA), the molecule that contains our genetic information, or to proteins which bind to the nDNA. Certain mutation
s can lead to cancer, and, according to de Grey, non-cancerous mutations and epimutations do not contribute to aging within a normal lifespan, so cancer is the only endpoint of these types of damage that must be addressed. A mutation in a functional gene of a cell can cause that cell to malfunction or to produce a malfunctioning product, because of the sheer number of cells, de Grey believes that redundancy takes care of this problem, although cells that have mutated to produce toxic products might have to be disabled. In de Grey's opinion, the effect of mutations and epimutations that really matters is cancer
, this is because if even one cell turns into a cancer cell it might spread and become deadly. This would need to be corrected by a cure for cancer, if any is ever found. The SENS program focuses on a strategy called "whole-body interdiction of lengthening telomeres" (WILT), which would be made possible by periodic regenerative medicine
treatments (see below). Restoring telomeres would protect the ends of DNA from being cut off after successive divisions since each one normally removes some which is at first the telomere.
that are important for energy
production. They contain their own genetic material, and mutations to their DNA can affect a cell’s ability to function properly. Indirectly, these mutations may accelerate many aspects of aging. Because of the highly oxidative environment in mitochondria and their lack of the sophisticated repair systems found in cell nucleus, mitochondrial mutations are believed to a be a major cause of progressive cellular degeneration. This would be corrected by allotopic expression
—moving the DNA
for mitochondria completely within the cellular nucleus
, where it is better protected. In humans, all but 13 proteins are already protected in this way. De Grey argues that experimental evidence demonstrates that the operation is feasible. However, a 2003 study showed that some mitochondrial proteins are too hydrophobic to survive the transport from the cytoplasm to the mitochondria, and this is perhaps one of the reasons that not all of the mitochondrial genes have migrated to the nucleus during the course of evolution.
s and other molecules that are no longer useful or which can be harmful. Those molecules which can’t be digested simply accumulate as junk inside our cells, which is readily detected in the form of lipofuscin
granules. Atherosclerosis
, macular degeneration
, liver spots on the skin and all kinds of neurodegenerative diseases (such as Alzheimer's disease) are associated with this problem. Junk inside cells might be removed by adding new enzymes to the cell's natural digestion
organ, the lysosome
. These enzymes would be taken from bacteria
, mold
s and other organisms that are known to completely digest animal bodies.
and other amyloidoses
. The oft-mentioned "toxins" that are identified as causes of many diseases most likely fit under this class.
s and the heart, causing them to become frailer with age. Loss of neurons in the substantia nigra
causes Parkinson's disease
, while loss of immune cells impairs the immune system
. Cell depletion can be partly corrected by therapies involving exercise and growth factor
s. But stem cell therapy, regenerative medicine
and tissue engineering
are almost certainly required for any more than just partial replacement of lost cells. De Grey points out that this research of stem cell treatments
is playing an increasingly important role in the international scientific community and progress is already occurring on many fronts. However, a large number of details are involved, and most such treatments are still experimental.
s, immune senescence, accumulation of visceral fat and type 2 diabetes
are caused by this. Cells sometimes enter a state of resistance to signals sent, as part of a process called apoptosis
, to instruct cells to destroy themselves. An example is the state known as cellular senescence. Cells in this state could be eliminated by forcing them to apoptose, and healthy cells would multiply to replace them. Cell killing with suicide gene
s or vaccine
s is suggested for making the cells undertake apoptosis.
, the tissue can lose its elasticity and cause problems including arteriosclerosis, presbyopia and weakened skin texture. These are chemical bonds between structures that are part of the body, but not within a cell
. In senescent people many of these become brittle and weak. De Grey proposes to further develop small-molecular drugs and enzyme
s to break links caused by sugar-bonding, known as advanced glycation endproduct
s, and other common forms of chemical linking.
(AmyloSENS) and oncogenomics
(OncoSENS), the SENS programme as a whole has been a highly controversial proposal, with many critics arguing that the SENS agenda is fanciful and the highly complicated biomedical phenomena involved in the aging process contain too many unknowns for SENS to be scientific or implementable in the foreseeable future. Cancer may well deserve special attention as an aging-associated disease
(OncoSENS), but the SENS claim that nuclear DNA damage only matters for aging because of cancer has been challenged.
In November 2005, 28 biogerontologists published a statement of criticism in EMBO reports
, "Science fact and the SENS agenda: what can we reasonably expect from ageing research?," arguing "each one of the specific proposals that comprise the SENS agenda is, at our present stage of ignorance, exceptionally optimistic," and that some of the specific proposals "will take decades of hard work [to be medically integrated], if [they] ever prove to be useful." The researchers argue that while there is "a rationale for thinking that we might eventually learn how to postpone human illnesses to an important degree," increased basic research, rather than the goal-directed approach of SENS, is presently the scientifically appropriate goal. This article was written in response to a July 2005 EMBO reports article previously published by de Grey and a response from de Grey was published in the same November issue. De Grey summarizes these events in "The biogerontology research community's evolving view of SENS," published on the Methuselah Foundation
website.
, which is owned by the Massachusetts Institute of Technology
, published an article by Sherwin Nuland, a Clinical Professor of Surgery at Yale University
and the author of "How We Die", that drew a skeptical portrait of Aubrey de Grey, at the time a computer associate in the Flybase Facility of the Department of Genetics at the University of Cambridge
. While admiring de Grey's intelligence, Nuland concluded that he "would surely destroy us in attempting to preserve us" because living for such long periods would undermine what it means to be human. In the same issue of the magazine, Jason Pontin
, the editor in chief and publisher of Technology Review, criticised de Grey. Writing an editor's letter, titled Against Transcendence, he questioned the usefulness and appropriateness of introducing transcendentalism, or transhumanism, into science. The April 2005 issue of Technology Review contained a reply by Aubrey de Grey and numerous comments from readers.
During June 2005 David Gobel, CEO and Co-founder of Methuselah Foundation offered Technology Review $20,000 to fund a prize competition to publicly clarify the viability of the SENS approach. In July 2005, Pontin announced a $20,000 prize, funded 50/50 by Methuselah Foundation and MIT Technology Review, open to any molecular biologist, with a record of publication in biogerontology, who could prove that SENS was "so wrong that it is unworthy of learned debate." Technology Review received five submissions to its Challenge. In March, of 2006, Technology Review announced that it had chosen a panel of judges for the Challenge. Three met the terms of the prize competition. They were published by Technology Review on June 9, 2006. Accompanying the three submissions were rebuttals by de Grey, and counter-responses to de Grey's rebuttals. On July 11, 2006, Technology Review published the results of the SENS Challenge.
In the end, no one won the $20,000 prize. The judges felt that no submission met the criterion of the challenge and disproved SENS, although they unanimously agreed that one submission, by Preston Estep
and his colleagues, was the most eloquent. Craig Venter succinctly expressed the prevailing opinion: "Estep et al. ... have not demonstrated that SENS is unworthy of discussion, but the proponents of SENS have not made a compelling case for it." Summarizing the judges' deliberations, Pontin wrote, "SENS is highly speculative. Many of its proposals have not been reproduced, nor could they be reproduced with today's scientific knowledge and technology. Echoing Myhrvold, we might charitably say that de Grey's proposals exist in a kind of antechamber of science, where they wait (possibly in vain) for independent verification. SENS does not compel the assent of many knowledgeable scientists; but neither is it demonstrably wrong." In a letter of dissent dated July 11, 2006 in Technology Review, Estep et al. criticized the ruling of the judges.
De Grey and other scientists in the general field have argued that the costs of a rapidly growing aging population will increase to the degree that the costs of an accelerated pace of aging research are easy to justify in terms of future costs avoided. Olshansky et al. 2006 argue, for example, that the total economic cost of Alzheimer's disease
in the US alone will increase from $80–100 billion today to more than $1 trillion in 2050. "Consider what is likely to happen if we don't [invest further in aging research]. Take, for instance, the impact of just one age-related disorder, Alzheimer disease (AD). For no other reason than the inevitable shifting demographics, the number of Americans stricken with AD will rise from 4 million today to as many as 16 million by midcentury. This means that more people in the United States will have AD by 2050 than the entire current population of the Netherlands. Globally, AD prevalence is expected to rise to 45 million by 2050, with three of every four patients with AD living in a developing nation. The US economic toll is currently $80–$100 billion, but by 2050 more than $1 trillion will be spent annually on AD and related dementias. The impact of this single disease will be catastrophic, and this is just one example."
and four SENS conferences
held. The first SENS roundtable was held in Oakland, California
on October, 2000, and the last SENS roundtable was held in Bethesda, Maryland
on July, 2004.
On March 30–31, 2007 a North American SENS symposium was held in Edmonton, Alberta, Canada
as the Edmonton Aging Symposium. Another SENS-related conference ("Understanding Aging") was held at UCLA
in Los Angeles
, California
on June 27-29, 2008
Four SENS conferences have been held at Queens' College, Cambridge
in England
. All the conferences were organized by de Grey and all featured world-class researchers in the field of biogerontology. The first SENS conference was held in September 2003 as the 10th Congress of the International Association of Biomedical Gerontology with the proceedings published in the Annals of the New York Academy of Sciences. The second SENS conference was held in September 2005 and was simply called Strategies for Engineered Negligible Senescence (SENS), Second Conference with the proceedings published in Rejuvenation Research
. The third SENS conference was held in September, 2007. The fourth SENS conference was held September 3–7, 2009 and, like the first three, it was at Queens' College, Cambridge in England, organized by de Grey. Videos of the presentations are available. A fifth SENS conference was held August 31 to September 3, 2011 at Queens' College, Cambridge in England.
co-founded by Michael Kope, Aubrey de Grey
, Jeff Hall, Sarah Marr and Kevin Perrott, which is based in California
, United States
. Its activities include SENS
-based research programs and public relations
work for the acceptance of and interest in scientific anti-aging research.
Before March 2009, the SENS research programme was mainly pursued by the Methuselah Foundation
, co-founded by Aubrey de Grey and David Gobel. The Methuselah Foundation
is most notable for establishing the Methuselah Mouse Prize, a monetary prize awarded to researchers who extend the lifespan of mice to unprecedented lengths.
Aubrey de Grey
Aubrey David Nicholas Jasper de Grey is an English author and theoretician in the field of gerontology, and the Chief Science Officer of the SENS Foundation. He is editor-in-chief of the academic journal Rejuvenation Research, author of The Mitochondrial Free Radical Theory of Aging and co-author...
gives to his proposal to research regenerative medical procedures to periodically repair all the age-related damage in the human body, thereby maintaining a youthful state indefinitely. The term first appeared in print in de Grey's 1999 book The Mitochondrial Free Radical Theory of Aging, and was later prefaced with the term "strategies" in the article Time to Talk SENS: Critiquing the Immutability of Human Aging De Grey argues for a "goal-directed rather than curiosity-driven" approach to the science of aging, and to this purpose he tentatively identifies seven "damages of aging" and their potential methods of treatments.
SENS has received media attention but has been criticized by some scientists. While many biogerontologists (scientists who study aging) find it "worthy of discussion" and SENS conferences feature important research in the field, some contend that de Grey's programme is too speculative given current scientific research, referring to it as "fantasy rather than science".
Framework
De Grey defines aging as "the set of accumulated side effects from metabolism that eventually kills us", and, more specifically, as follows: "a collection of cumulative changes to the molecular
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
and cellular
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
structure of an adult
Adult
An adult is a human being or living organism that is of relatively mature age, typically associated with sexual maturity and the attainment of reproductive age....
organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
, which result in essential metabolic
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
processes, but which also, once they progress far enough, increasingly disrupt metabolism, resulting in pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
and death."
As de Grey states, "geriatrics
Geriatrics
Geriatrics is a sub-specialty of internal medicine and family medicine that focuses on health care of elderly people. It aims to promote health by preventing and treating diseases and disabilities in older adults. There is no set age at which patients may be under the care of a geriatrician, or...
is the attempt to stop damage from causing pathology; traditional gerontology
Gerontology
Gerontology is the study of the social, psychological and biological aspects of aging...
is the attempt to stop metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
from causing damage; and the SENS (engineering) approach is to eliminate the damage periodically, so keeping its abundance below the level that causes any pathology." His approach to biomedical gerontology
Gerontology
Gerontology is the study of the social, psychological and biological aspects of aging...
("anti-aging medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
") is thus distinctive because of its emphasis on rejuvenation
Rejuvenation
Rejuvenation may refer to:*Rejuvenation , reversing the aging process*Rejuvenation , when the base level that a river is flowing down to is lowered*Rejuvenation , 1974*Rejuvenation , 2009...
rather than attempting to slow the aging process.
He identifies what he believes to be the seven biological causes of senescence. According to de Grey, the causes of aging in humans are:
- cell loss or atrophy (without replacement)
- oncogenicOncologyOncology is a branch of medicine that deals with cancer...
nuclearCell nucleusIn cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
mutationMutationIn molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s and epimutations, - cell senescenceSenescenceSenescence or biological aging is the change in the biology of an organism as it ages after its maturity. Such changes range from those affecting its cells and their function to those affecting the whole organism...
(Death-resistant cells), - mitochondrial mutations,
- Intracellular junk or junk inside cells (lysosomalLysosomethumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
aggregates), - extracellular junk or junk outside cells (extracellular aggregates),
- random extracellular cross-linking.
For each of these problems, de Grey outlines possible solutions, with a research and a clinical component. The clinical component is required because in some of the proposed therapies, feasibility has already been proven, but not completely applied and approved for use by human beings. He believes we will be able to apply these solutions before we completely understand the targeted aging mechanisms, which will take longer. He states that the goals work together to eliminate known causes of human senescence, are concrete, seem achievable, and are considered feasible by experts in the applicable fields. The goals were said to be taken from classical literature describing the biological causes of senescence.
De Grey proposes that engineered negligible senescence therapies could extend the human lifetime by many centuries or millennia, as early therapies give them enough time to seek more effective therapies later on. He describes an actuarial escape velocity of life extension
Life extension
Life extension science, also known as anti-aging medicine, experimental gerontology, and biomedical gerontology, is the study of slowing down or reversing the processes of aging to extend both the maximum and average lifespan...
, when advances in senescence treatment come rapidly enough to save the lives of the oldest beneficiaries of the previous treatments.
Cancer-causing nuclear mutations/epimutations—OncoSENS
These are changes to the nuclear DNADNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
(nDNA), the molecule that contains our genetic information, or to proteins which bind to the nDNA. Certain mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s can lead to cancer, and, according to de Grey, non-cancerous mutations and epimutations do not contribute to aging within a normal lifespan, so cancer is the only endpoint of these types of damage that must be addressed. A mutation in a functional gene of a cell can cause that cell to malfunction or to produce a malfunctioning product, because of the sheer number of cells, de Grey believes that redundancy takes care of this problem, although cells that have mutated to produce toxic products might have to be disabled. In de Grey's opinion, the effect of mutations and epimutations that really matters is cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, this is because if even one cell turns into a cancer cell it might spread and become deadly. This would need to be corrected by a cure for cancer, if any is ever found. The SENS program focuses on a strategy called "whole-body interdiction of lengthening telomeres" (WILT), which would be made possible by periodic regenerative medicine
Regenerative medicine
Regenerative medicine is the "process of replacing or regenerating human cells, tissues or organs to restore orestablish normal function". This field holds the promise of regenerating damaged tissues and organs in the body by replacing damaged tissue and/or by stimulating the body's own repair...
treatments (see below). Restoring telomeres would protect the ends of DNA from being cut off after successive divisions since each one normally removes some which is at first the telomere.
Mitochondrial mutations—MitoSENS
Mitochondria are components in our cellsCell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
that are important for energy
Energy
In physics, energy is an indirectly observed quantity. It is often understood as the ability a physical system has to do work on other physical systems...
production. They contain their own genetic material, and mutations to their DNA can affect a cell’s ability to function properly. Indirectly, these mutations may accelerate many aspects of aging. Because of the highly oxidative environment in mitochondria and their lack of the sophisticated repair systems found in cell nucleus, mitochondrial mutations are believed to a be a major cause of progressive cellular degeneration. This would be corrected by allotopic expression
Allotopic expression
Allotopic expression refers to expression from the nuclear genome of genes that normally are expressed only from the mitochondrial genome. Biomedically engineered AE has been suggested as a possible future tool in gene therapy of certain mitochondria-related diseases , however this view is...
—moving the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
for mitochondria completely within the cellular nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, where it is better protected. In humans, all but 13 proteins are already protected in this way. De Grey argues that experimental evidence demonstrates that the operation is feasible. However, a 2003 study showed that some mitochondrial proteins are too hydrophobic to survive the transport from the cytoplasm to the mitochondria, and this is perhaps one of the reasons that not all of the mitochondrial genes have migrated to the nucleus during the course of evolution.
Intracellular junk—LysoSENS
Our cells are constantly breaking down proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s and other molecules that are no longer useful or which can be harmful. Those molecules which can’t be digested simply accumulate as junk inside our cells, which is readily detected in the form of lipofuscin
Lipofuscin
Lipofuscin is the name given to finely granular yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion. It is considered one of the aging or "wear-and-tear" pigments, found in the liver, kidney, heart muscle, adrenals, nerve cells, and ganglion cells...
granules. Atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
, macular degeneration
Macular degeneration
Age-related macular degeneration is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults...
, liver spots on the skin and all kinds of neurodegenerative diseases (such as Alzheimer's disease) are associated with this problem. Junk inside cells might be removed by adding new enzymes to the cell's natural digestion
Digestion
Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....
organ, the lysosome
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
. These enzymes would be taken from bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, mold
Mold
Molds are fungi that grow in the form of multicellular filaments called hyphae. Molds are not considered to be microbes but microscopic fungi that grow as single cells called yeasts...
s and other organisms that are known to completely digest animal bodies.
Extracellular junk—AmyloSENS
Harmful junk protein can also accumulate outside of our cells. Junk outside cells might be removed by enhanced phagocytosis (the normal process used by the immune system), and small drugs able to break chemical beta-bonds. The large junk in this class can be removed surgically. Junk here means useless things accumulated by a body, but which cannot be digested or removed by its processes, such as the amyloid plaques characteristic of Alzheimer's diseaseAlzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
and other amyloidoses
Amyloidosis
In medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...
. The oft-mentioned "toxins" that are identified as causes of many diseases most likely fit under this class.
Cell loss and atrophy—RepleniSENS
Some of the cells in our bodies cannot be replaced, or can be only replaced very slowly—more slowly than they die. This decrease in cell number affects some of the most important tissues of the body. Muscle cells are lost in skeletal muscleSkeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
s and the heart, causing them to become frailer with age. Loss of neurons in the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
causes Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, while loss of immune cells impairs the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. Cell depletion can be partly corrected by therapies involving exercise and growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
s. But stem cell therapy, regenerative medicine
Regenerative medicine
Regenerative medicine is the "process of replacing or regenerating human cells, tissues or organs to restore orestablish normal function". This field holds the promise of regenerating damaged tissues and organs in the body by replacing damaged tissue and/or by stimulating the body's own repair...
and tissue engineering
Tissue engineering
Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physio-chemical factors to improve or replace biological functions...
are almost certainly required for any more than just partial replacement of lost cells. De Grey points out that this research of stem cell treatments
Stem cell treatments
Stem cell treatments are a type of intervention strategy that introduces new cells into damaged tissue in order to treat disease or injury. Many medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering...
is playing an increasingly important role in the international scientific community and progress is already occurring on many fronts. However, a large number of details are involved, and most such treatments are still experimental.
Cell senescence—ApoptoSENS
This is a phenomenon where the cells are no longer able to divide, but also do not die and let others divide. They may also do other things that they are not supposed to do, like secreting proteins that could be harmful. Degeneration of jointJoint
A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
s, immune senescence, accumulation of visceral fat and type 2 diabetes
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
are caused by this. Cells sometimes enter a state of resistance to signals sent, as part of a process called apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, to instruct cells to destroy themselves. An example is the state known as cellular senescence. Cells in this state could be eliminated by forcing them to apoptose, and healthy cells would multiply to replace them. Cell killing with suicide gene
Suicide gene
A suicide gene, in genetics, will cause a cell to kill itself through apoptosis. Activation of these genes can be due to many processes, but the main cellular "switch" to induce apoptosis is the p53 protein....
s or vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
s is suggested for making the cells undertake apoptosis.
Extracellular crosslinks—GlycoSENS
Cells are held together by special linking proteins. When too many cross-links form between cells in a tissueBiological tissue
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
, the tissue can lose its elasticity and cause problems including arteriosclerosis, presbyopia and weakened skin texture. These are chemical bonds between structures that are part of the body, but not within a cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. In senescent people many of these become brittle and weak. De Grey proposes to further develop small-molecular drugs and enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s to break links caused by sugar-bonding, known as advanced glycation endproduct
Advanced glycation endproduct
An advanced glycation end-product is the result of a chain of chemical reactions after an initial glycation reaction. The intermediate products are known, variously, as Amadori, Schiff base and Maillard products, named after the researchers who first described them. An advanced glycation...
s, and other common forms of chemical linking.
Scientific controversy
While some fields mentioned as branches of SENS are broadly supported by the medical research community, i.e. stem cell research (RepleniSENS), anti-Alzheimers researchAlzheimer's disease clinical research
As of August 2010 there were more than 800 clinical trials under way to understand and treat Alzheimer's disease. 149 of these studies were human phase three trials, the last step before U.S. Food and Drug Administration approval and marketing....
(AmyloSENS) and oncogenomics
Oncogenomics
Oncogenomics is relatively new sub-field of genomics, which applies high throughput technologies to characterize genes associated with cancer. Oncogenomics is synonymous with "cancer genomics". Cancer is a genetic disease caused by accumulation of mutations to DNA leading to unrestrained cell...
(OncoSENS), the SENS programme as a whole has been a highly controversial proposal, with many critics arguing that the SENS agenda is fanciful and the highly complicated biomedical phenomena involved in the aging process contain too many unknowns for SENS to be scientific or implementable in the foreseeable future. Cancer may well deserve special attention as an aging-associated disease
Aging-associated diseases
An aging-associated disease is a disease that is seen with increasing frequency with increasing senescence. Age-associated diseases are to be distinguished from the aging process itself because all adult animals age, but not all adult animals experience all age-associated diseases...
(OncoSENS), but the SENS claim that nuclear DNA damage only matters for aging because of cancer has been challenged.
In November 2005, 28 biogerontologists published a statement of criticism in EMBO reports
EMBO Journal
The EMBO Journal is a peer-reviewed scientific journal focusing on full-length papers describing original research of general interest in molecular biology and related areas. The journal's editorial office is in Heidelberg, Germany. The journal is published by Nature Publishing Group on behalf of...
, "Science fact and the SENS agenda: what can we reasonably expect from ageing research?," arguing "each one of the specific proposals that comprise the SENS agenda is, at our present stage of ignorance, exceptionally optimistic," and that some of the specific proposals "will take decades of hard work [to be medically integrated], if [they] ever prove to be useful." The researchers argue that while there is "a rationale for thinking that we might eventually learn how to postpone human illnesses to an important degree," increased basic research, rather than the goal-directed approach of SENS, is presently the scientifically appropriate goal. This article was written in response to a July 2005 EMBO reports article previously published by de Grey and a response from de Grey was published in the same November issue. De Grey summarizes these events in "The biogerontology research community's evolving view of SENS," published on the Methuselah Foundation
Methuselah Foundation
The Methuselah Foundation studies methods of extending lifespan. It is a non-profit 501 volunteer organization, co-founded by Aubrey de Grey and David Gobel, which is based in Springfield, Virginia, United States...
website.
De Grey Technology Review controversy
In February 2005, Technology ReviewTechnology Review
Technology Review is a magazine published by the Massachusetts Institute of Technology. It was founded in 1899 as "The Technology Review", and was re-launched without the "The" in its name on April 23, 1998 under then publisher R. Bruce Journey...
, which is owned by the Massachusetts Institute of Technology
Massachusetts Institute of Technology
The Massachusetts Institute of Technology is a private research university located in Cambridge, Massachusetts. MIT has five schools and one college, containing a total of 32 academic departments, with a strong emphasis on scientific and technological education and research.Founded in 1861 in...
, published an article by Sherwin Nuland, a Clinical Professor of Surgery at Yale University
Yale University
Yale University is a private, Ivy League university located in New Haven, Connecticut, United States. Founded in 1701 in the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States...
and the author of "How We Die", that drew a skeptical portrait of Aubrey de Grey, at the time a computer associate in the Flybase Facility of the Department of Genetics at the University of Cambridge
University of Cambridge
The University of Cambridge is a public research university located in Cambridge, United Kingdom. It is the second-oldest university in both the United Kingdom and the English-speaking world , and the seventh-oldest globally...
. While admiring de Grey's intelligence, Nuland concluded that he "would surely destroy us in attempting to preserve us" because living for such long periods would undermine what it means to be human. In the same issue of the magazine, Jason Pontin
Jason Pontin
-Biography:Pontin was born on May 11, 1967 in London, and raised in Northern California. He was educated in England, at Harrow School and Oxford University....
, the editor in chief and publisher of Technology Review, criticised de Grey. Writing an editor's letter, titled Against Transcendence, he questioned the usefulness and appropriateness of introducing transcendentalism, or transhumanism, into science. The April 2005 issue of Technology Review contained a reply by Aubrey de Grey and numerous comments from readers.
During June 2005 David Gobel, CEO and Co-founder of Methuselah Foundation offered Technology Review $20,000 to fund a prize competition to publicly clarify the viability of the SENS approach. In July 2005, Pontin announced a $20,000 prize, funded 50/50 by Methuselah Foundation and MIT Technology Review, open to any molecular biologist, with a record of publication in biogerontology, who could prove that SENS was "so wrong that it is unworthy of learned debate." Technology Review received five submissions to its Challenge. In March, of 2006, Technology Review announced that it had chosen a panel of judges for the Challenge. Three met the terms of the prize competition. They were published by Technology Review on June 9, 2006. Accompanying the three submissions were rebuttals by de Grey, and counter-responses to de Grey's rebuttals. On July 11, 2006, Technology Review published the results of the SENS Challenge.
In the end, no one won the $20,000 prize. The judges felt that no submission met the criterion of the challenge and disproved SENS, although they unanimously agreed that one submission, by Preston Estep
Preston Estep
Preston W. Estep III is an American biologist and science and technology advocate. He is a graduate of Cornell University, where he did neuroscience research, and he earned a Ph.D. in Genetics from Harvard University. He did his doctoral research in the laboratory of genomics pioneer Professor...
and his colleagues, was the most eloquent. Craig Venter succinctly expressed the prevailing opinion: "Estep et al. ... have not demonstrated that SENS is unworthy of discussion, but the proponents of SENS have not made a compelling case for it." Summarizing the judges' deliberations, Pontin wrote, "SENS is highly speculative. Many of its proposals have not been reproduced, nor could they be reproduced with today's scientific knowledge and technology. Echoing Myhrvold, we might charitably say that de Grey's proposals exist in a kind of antechamber of science, where they wait (possibly in vain) for independent verification. SENS does not compel the assent of many knowledgeable scientists; but neither is it demonstrably wrong." In a letter of dissent dated July 11, 2006 in Technology Review, Estep et al. criticized the ruling of the judges.
Social and economic implications
According to de Grey, of the roughly 150,000 people who die each day across the globe, about two thirds — 100,000 per day — die of age-related causes. In industrialized nations, the proportion is much higher, reaching 90%.De Grey and other scientists in the general field have argued that the costs of a rapidly growing aging population will increase to the degree that the costs of an accelerated pace of aging research are easy to justify in terms of future costs avoided. Olshansky et al. 2006 argue, for example, that the total economic cost of Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
in the US alone will increase from $80–100 billion today to more than $1 trillion in 2050. "Consider what is likely to happen if we don't [invest further in aging research]. Take, for instance, the impact of just one age-related disorder, Alzheimer disease (AD). For no other reason than the inevitable shifting demographics, the number of Americans stricken with AD will rise from 4 million today to as many as 16 million by midcentury. This means that more people in the United States will have AD by 2050 than the entire current population of the Netherlands. Globally, AD prevalence is expected to rise to 45 million by 2050, with three of every four patients with AD living in a developing nation. The US economic toll is currently $80–$100 billion, but by 2050 more than $1 trillion will be spent annually on AD and related dementias. The impact of this single disease will be catastrophic, and this is just one example."
SENS meetings
There have been four SENS roundtablesRound table
A round table is a table which has no "head" and no "sides", and therefore no one person sitting at it is given a privileged position and all are treated as equals. The idea stems from the Arthurian legend about the Knights of the Round Table in Camelot....
and four SENS conferences
Academic conference
An academic conference or symposium is a conference for researchers to present and discuss their work. Together with academic or scientific journals, conferences provide an important channel for exchange of information between researchers.-Overview:Conferences are usually composed of various...
held. The first SENS roundtable was held in Oakland, California
Oakland, California
Oakland is a major West Coast port city on San Francisco Bay in the U.S. state of California. It is the eighth-largest city in the state with a 2010 population of 390,724...
on October, 2000, and the last SENS roundtable was held in Bethesda, Maryland
Bethesda, Maryland
Bethesda is a census designated place in southern Montgomery County, Maryland, United States, just northwest of Washington, D.C. It takes its name from a local church, the Bethesda Meeting House , which in turn took its name from Jerusalem's Pool of Bethesda...
on July, 2004.
On March 30–31, 2007 a North American SENS symposium was held in Edmonton, Alberta, Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
as the Edmonton Aging Symposium. Another SENS-related conference ("Understanding Aging") was held at UCLA
University of California, Los Angeles
The University of California, Los Angeles is a public research university located in the Westwood neighborhood of Los Angeles, California, USA. It was founded in 1919 as the "Southern Branch" of the University of California and is the second oldest of the ten campuses...
in Los Angeles
Los Ángeles
Los Ángeles is the capital of the province of Biobío, in the commune of the same name, in Region VIII , in the center-south of Chile. It is located between the Laja and Biobío rivers. The population is 123,445 inhabitants...
, California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...
on June 27-29, 2008
Four SENS conferences have been held at Queens' College, Cambridge
Queens' College, Cambridge
Queens' College is a constituent college of the University of Cambridge, England.The college was founded in 1448 by Margaret of Anjou , and refounded in 1465 by Elizabeth Woodville...
in England
England
England is a country that is part of the United Kingdom. It shares land borders with Scotland to the north and Wales to the west; the Irish Sea is to the north west, the Celtic Sea to the south west, with the North Sea to the east and the English Channel to the south separating it from continental...
. All the conferences were organized by de Grey and all featured world-class researchers in the field of biogerontology. The first SENS conference was held in September 2003 as the 10th Congress of the International Association of Biomedical Gerontology with the proceedings published in the Annals of the New York Academy of Sciences. The second SENS conference was held in September 2005 and was simply called Strategies for Engineered Negligible Senescence (SENS), Second Conference with the proceedings published in Rejuvenation Research
Rejuvenation Research
Rejuvenation Research is a multidisciplinary peer-reviewed bimonthly scientific journal published by Mary Ann Liebert that investigates rejuvenation therapies.The editor-in-chief is Aubrey de Grey...
. The third SENS conference was held in September, 2007. The fourth SENS conference was held September 3–7, 2009 and, like the first three, it was at Queens' College, Cambridge in England, organized by de Grey. Videos of the presentations are available. A fifth SENS conference was held August 31 to September 3, 2011 at Queens' College, Cambridge in England.
SENS Foundation
The SENS Foundation is a non-profit organizationNon-profit organization
Nonprofit organization is neither a legal nor technical definition but generally refers to an organization that uses surplus revenues to achieve its goals, rather than distributing them as profit or dividends...
co-founded by Michael Kope, Aubrey de Grey
Aubrey de Grey
Aubrey David Nicholas Jasper de Grey is an English author and theoretician in the field of gerontology, and the Chief Science Officer of the SENS Foundation. He is editor-in-chief of the academic journal Rejuvenation Research, author of The Mitochondrial Free Radical Theory of Aging and co-author...
, Jeff Hall, Sarah Marr and Kevin Perrott, which is based in California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...
, United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
. Its activities include SENS
Sens
Sens is a commune in the Yonne department in Burgundy in north-central France.Sens is a sub-prefecture of the department. It is crossed by the Yonne and the Vanne, which empties into the Yonne here.-History:...
-based research programs and public relations
Public relations
Public relations is the actions of a corporation, store, government, individual, etc., in promoting goodwill between itself and the public, the community, employees, customers, etc....
work for the acceptance of and interest in scientific anti-aging research.
Before March 2009, the SENS research programme was mainly pursued by the Methuselah Foundation
Methuselah Foundation
The Methuselah Foundation studies methods of extending lifespan. It is a non-profit 501 volunteer organization, co-founded by Aubrey de Grey and David Gobel, which is based in Springfield, Virginia, United States...
, co-founded by Aubrey de Grey and David Gobel. The Methuselah Foundation
Methuselah Foundation
The Methuselah Foundation studies methods of extending lifespan. It is a non-profit 501 volunteer organization, co-founded by Aubrey de Grey and David Gobel, which is based in Springfield, Virginia, United States...
is most notable for establishing the Methuselah Mouse Prize, a monetary prize awarded to researchers who extend the lifespan of mice to unprecedented lengths.
See also
- Actuarial escape velocity
- Aging-associated diseasesAging-associated diseasesAn aging-associated disease is a disease that is seen with increasing frequency with increasing senescence. Age-associated diseases are to be distinguished from the aging process itself because all adult animals age, but not all adult animals experience all age-associated diseases...
- List of life extension topics
- Pro-aging trancePro-aging tranceThe "pro-aging trance" is a term coined by Aubrey de Grey to describe "the impulsion to leap to embarrassingly unjustified conclusions in order to put the horror of aging out of one’s mind"...
- Rejuvenation ResearchRejuvenation ResearchRejuvenation Research is a multidisciplinary peer-reviewed bimonthly scientific journal published by Mary Ann Liebert that investigates rejuvenation therapies.The editor-in-chief is Aubrey de Grey...
- ProtoscienceProtoscienceIn the philosophy of science, a protoscience is an area of scientific endeavor that is in the process of becoming established. Protoscience is distinguished from pseudoscience by its standard practices of good science, such as a willingness to be disproven by new evidence, or to be replaced by a...
- American Academy of Anti-Aging MedicineAmerican Academy of Anti-Aging MedicineThe American Academy of Anti-Aging Medicine is a United States registered 501 nonprofit organization that promotes the field of anti-aging medicine and trains and certifies physicians in this specialty. As of 2011, approximately 26,000 practitioners had been given certificates...