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Strategies for engineered negligible senescence

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SENS redirects here. SENS is also the acronym for the Samsung Electronics Notebook Series.
Aubrey de Grey is Editor-in-Chief of the Rejuvenation Research journal, which deals with topics related to engineered negligible senescence. The journal's editorial board includes figures from the relevant areas of biology and its social context, including stem cell therapy, tissue engineering, gene therapy, public policy, cancer therapies, and demography.

Engineered negligible senescence is a term meaning an engineered prevention or reversal of cellular aging, which is called senescence in biology.

The term was coined by Cambridge associate and biogerontologist Aubrey de Grey around 2002, and is used in the context of his life extension medical proposal, Strategies for Engineered Negligible Senescence (SENS). It has been reported on by many news sources, including the BBC, the New York Times, Fortune Magazine, and Popular Science

Proposal

As Aubrey 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 periodically to eliminate the damage, so keeping its abundance below the level that causes any pathology."

The arrows with flat heads are a notation meaning 'inhibits,' used in the literature of gene expression and gene regulation.

De Grey has published papers in this area in prominent journals with some of biogerontology's foremost researchers, including Bruce Ames, Leonid Gavrilov, and S. Jay Olshansky, as well as other scientists such as Gregory Stock.[1] De Grey has also received support from other prominent scientists, such as William Haseltine, the biotech pioneer of Human Genome Sciences, who in March 2005 stated regarding the Methuselah Mouse Prize (see section below), "there’s nothing to compare with this effort, and it has already contributed significantly to the awareness that regenerative medicine is a near term reality, not an if."

Escape velocity

De Grey proposes that engineered negligible senescence therapies could extend humans' lives by many centuries or more, as early therapies give them enough time to see more effective therapies later on. De Grey describes an "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.

The seven causes of aging

De Grey defines aging as "the set of accumulated side effects from metabolism that eventually kills us,"[2] , and his proposal identifies what he believes to be the seven biological causes of senescence and outlines possible solutions, each with both 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. De Grey believes we will be able to apply these solutions before we completely understand the targeted aging mechanisms, which will take longer.

De Grey claims 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.

Cell loss or atrophy

Cell depletion can be partly corrected by therapies involving exercise and growth factors. But stem cell therapy is almost certainly required for any more than just partial replacement of lost cells. This research would involve a large number of details, but is occurring on many fronts anyway.

Nuclear mutations and epimutations

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 Dr. de Grey belives that redundancy takes care of this problem although cells that have mutated to produce toxic products might have to be disabled. In Dr. 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 was to be corrected by whole-body interdiction of lengthening telomeres, or any other cure for cancer, if any is ever found.

Mutant mitochondria

Because of the highly oxidative environment in mitochondria and their lack of the sophisticated repair systems found in cell nucleus, mitochodrial mutations are believed to a be a major cause of progressive cellular degeneration. This was to be corrected by 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. It has been experimentally shown the operation is feasible.

Cellular senescence

Cellular senescence might be corrected by forcing senescent cells to destroy themselves, a process called apoptosis. Cell killing with suicide genes or vaccines was suggested for making the cells do apoptosis. Healthy cells would multiply to replace them.

Extracellular cross-links

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. The proposal was to further develop small-molecular drugs and enzymes to break links caused by sugar-bonding (glucosylation), and other common forms of chemical linking.

Junk outside 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 disease.

Junk inside cells

Junk inside cells might be removed by adding new enzymes to the cell's natural digestion organ, the lysozome. These enzymes would be taken from bacteria, molds and other organisms that are known to completely digest animal bodies.

Methuselah Mouse Prize

Main article at Methuselah Mouse Prize

In 2003, de Grey co-founded (with David Gobel) the Methuselah Mouse Prize, a prize designed to accelerate research into effective life extension interventions by awarding monetary prizes to researchers who extend the lifespan of mice to unprecedented lengths. Regarding this, De Grey stated in March 2005, "if we are to bring about real regenerative therapies that will benefit not just future generations, but those of us who are alive today, we must encourage scientists to work on the problem of aging." The prize reached $1.5 million USD in August 2005. De Grey believes that once this objective has been achieved in mice, a large amount of funding will be diverted to this kind of research, which would accelerate progress.

Related articles

External links

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