Elderly hospital patient

Aging and How to Defeat It

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Aging is caused by the accumulation of damage in the human body. Aging damage eventually leads to age-related disease and ultimately death. Medical therapies designed to repair this damage could restore the body to a youthful and healthy state.

The Aging Process

Aging is caused by the long-term accumulation of damage in the human body at the molecular and cellular level. This damage occurs as a side-effect of normal metabolism—the process that keeps the body alive from day to day. As aging damage accumulates in the body's molecular and cellular structures, it eventually leads to increasing frailty and disability due to age-related diseases such as cancer, diabetes, heart disease, Alzheimer's disease, and Parkinson's disease. This downward spiral caused by the aging process ultimately ends in death.

Approaches To Fight Aging

Approaches to fight aging
Flat-headed arrows mean "inhibits."

There are three approaches to fight aging: geriatrics, gerontology, and engineering. Geriatrics tries to slow the rate at which age-related diseases progress once they develop and alleviate their symptoms. This approach is practiced by mainstream medicine and ranges from statin drugs to pain management techniques. Since it can only slow disease progression by months to a few years at most, it is also the least effective. Gerontology attempts to slow the rate at which metabolism lays down aging damage thus slowing the rate at which all age-related diseases occur. This approach pursues the development of substances that have the potential to extend the lifespan of mice or mimic the effects of calorie restriction, genetic manipulation, and evolutionary selection of laboratory organisms. Resveratrol and rapamycin are examples of these kinds of substances. While these interventions have been shown to substantially postpone the effects of aging in laboratory organisms such as worms, fruit flies, and mice, it is not known if any of them will significantly slow aging in humans. Even if they will work well, merely slowing the rate at which disease occurs will always be a losing battle. The engineering approach referred to as "Strategies for Engineered Negligible Senescence" (SENS) or "rejuvenation biotechnology" seeks to reverse aging by repairing the damage caused by metabolism instead of attempting to merely slow down the occurrence or progression of disease. By periodically repairing this disease-causing damage, SENS proposes to restore a chronologically old body to a biologically youthful state thus curing any age-related frailty and disease while also maintaining the body's youthfulness indefinitely.

The Human Body and Vintage Cars

To better understand the engineering approach, consider an analogy between the human body and vintage cars. The human body is similar to complicated machines like cars. There are vintage cars on the road today that were built more than 100 years ago. Clearly, those cars would not be running if damage was allowed to accumulate in the absence of periodic maintenance and repair. The human body is much more complicated than a car, and the human aging process is similarly more complicated. However, the process is the same in principle; the repair of aging damage should maintain the human body in a healthy state for an indefinite period of time just like maintenance and repair of cars can keep them running just as well as when they were new.

Repairing The Damage

Dr. Aubrey de Grey was the first to compile a list of all the major types of aging damage and suggest that an engineering approach in the form of SENS could defeat aging entirely instead of merely postponing disease like the traditional approaches. Currently, SENS is comprised of seven major types of medical therapies addressing seven major categories of aging damage.

We can be confident that this list of aging damage is complete, because scientists have not discovered any new kinds of damage in nearly a generation despite the fact that research into aging has been accelerating and that scientists have had ever-increasingly powerful tools with which to investigate the aging body. This implies that if there are other kinds of disease-causing damage that we do not know about, they probably do not contribute as much to aging damage to make a difference in a normal lifespan.

Damage Location
Damage Type
Age-Related DiseasesSENS Therapy
Outside cells
Cell loss
Discovered in 1955
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.
Alzheimer's disease
Heart disease
Immune system dysfunction
Muscle atrophy
Parkinson's disease
Skin aging
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.
Death-resistant cells
Discovered in 1965
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)
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.
Junk outside cells
Discovered in 1907
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
Multiple organ failure (possibly affects people over 110 years old)
Stroke
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.
Tissue stiffening
Discovered in 1958 and 1981
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
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.

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.
Inside cells
Junk inside cells
Discovered in 1959
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
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.
Mutations in the cell's mitochondria
Discovered in 1972
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) 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 nucleus
Discovered in 1959 and 1982
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 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.

There is often speculation that shortened telomeres (the caps on the ends of chromosomes which help preserve chromosome integrity) and DNA mutations in the cell's nucleus (the kind that does not lead to cancer) constitute another kind of damage that may lead to age-related disease, but this is controversial. If this turns out to be true, this kind of damage will need to be repaired as well.

Timeframes

SENS therapies will have to be fully developed and tested on mice and then adapted for human use. According to Dr. de Grey, with funding of $100 million per year for a decade these therapies could be tested on mice within 10 years. After being successfully applied to mice, the therapies will have a 50 percent chance of being ready for human use in 15 years. If lack of funding or unforeseen obstacles slow progress, it could take longer than 25 years for SENS therapies to be fully developed. Regardless of the accuracy of this timeframe, it is clear that the sooner these therapies start to be developed, the sooner aging will be defeated.

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