Accelerated aging disease
Encyclopedia
A DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair
.
DNA repair defects are seen in nearly all of the diseases described as accelerated aging disease, in which various tissue
s, organ
s or systems of the human body age
prematurely. Because the accelerated aging diseases display different aspects of aging, but never every aspect, they are often called segmental progerias by biogerontologists.
essential for base excision repair
kills the embryo
—it is too lethal to display symptoms (much less symptoms of cancer or "accelerated aging").
Rothmund-Thomson syndrome and xeroderma pigmentosum display symptoms dominated by vulnerability to cancer, whereas progeria and Werner syndrome show the most features of "accelerated aging". Hereditary nonpolyposis colorectal cancer
(HNPCC) is very often caused by a defective MSH2
gene leading to defective mismatch repair
, but displays no symptoms of "accelerated aging". Some DNA repair defects manifest as neurodegeneration
rather than as cancer or
"accelerated aging".
, etc. are associated with increased mortality
. Without reliable biomarkers
of aging it is hard to support the claim that a disease condition represents more than accelerated mortality.
Against this position other biogerontologists argue that premature aging phenotype
s are identifiable symptoms associated with mechanisms of molecular damage. The fact that these phenotypes are widely recognized justifies classification of the relevant diseases as "accelerated aging". Such conditions, it is argued, are readily distinguishable from genetic disease
s associated with increased mortality, but not associated with an aging phenotype, such as cystic fibrosis
and sickle cell anemia
. It is further argued that segmental aging phenotype is a natural part of aging insofar as genetic variation leads to some people being more disposed than others to aging-associated diseases
such as cancer
and Alzheimer's disease
.
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
.
DNA repair defects are seen in nearly all of the diseases described as accelerated aging disease, in which various tissue
Biological 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...
s, organ
Organ (anatomy)
In biology, an organ is a collection of tissues joined in structural unit to serve a common function. Usually there is a main tissue and sporadic tissues . The main tissue is the one that is unique for the specific organ. For example, main tissue in the heart is the myocardium, while sporadic are...
s or systems of the human body age
Senescence
Senescence 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...
prematurely. Because the accelerated aging diseases display different aspects of aging, but never every aspect, they are often called segmental progerias by biogerontologists.
Examples
Some of the examples include:- Ataxia telangiectasiaAtaxia telangiectasiaAtaxia telangiectasia is a rare, neurodegenerative, inherited disease that affects many parts of the body and causes severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease...
- Bloom syndromeBloom syndromeBloom's syndrome , also known as Bloom–Torre–Machacek syndrome, is a rare autosomal recessive chromosomal disorder characterized by a high frequency of breaks and rearrangements in an affected person's chromosomes. The condition was discovered and first described by dermatologist Dr...
- Cockayne's syndrome
- Fanconi's anaemia
- ProgeriaProgeriaProgeria is an extremely rare genetic condition wherein symptoms resembling aspects of aging are manifested at an early age. The word progeria comes from the Greek words "pro" , meaning "before", and "géras" , meaning "old age"...
(Hutchinson-Gilford Progeria syndrome) - Rothmund-Thomson syndromeRothmund-Thomson syndromeRothmund–Thomson syndrome , also known as poikiloderma atrophicans with cataract or poikiloderma congenitale, is a rare autosomal recessive skin condition originally described by August von Rothmund in 1868. Matthew Sydney Thomson published further descriptions in 1936.There have been several...
- Trichothiodystrophy
- Werner syndromeWerner syndromeWerner syndrome is a very rare, autosomal recessive disorder characterized by the appearance of premature aging....
- Xeroderma pigmentosumXeroderma pigmentosumXeroderma pigmentosum, or XP, is an autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet light is deficient. In extreme cases, all exposure to sunlight must be forbidden, no matter how small. Multiple basal cell carcinomas and other skin...
DNA repair defects distinguished from "accelerated aging"
Most of the DNA repair deficiency diseases show varying degrees of "accelerated aging" or cancer (usually some of both). But elimination of any geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
essential for base excision repair
Base excision repair
In biochemistry and genetics, base excision repair is a cellular mechanism that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky...
kills the embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
—it is too lethal to display symptoms (much less symptoms of cancer or "accelerated aging").
Rothmund-Thomson syndrome and xeroderma pigmentosum display symptoms dominated by vulnerability to cancer, whereas progeria and Werner syndrome show the most features of "accelerated aging". Hereditary nonpolyposis colorectal cancer
Hereditary nonpolyposis colorectal cancer
Lynch syndrome is an autosomal dominant genetic condition which has a high risk of colon cancer as well as other cancers including endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin...
(HNPCC) is very often caused by a defective MSH2
MSH2
MSH2 is a gene commonly associated with Hereditary nonpolyposis colorectal cancer.-Interactions:MSH2 has been shown to interact with Exonuclease 1, MSH3, MSH6, CHEK2, MAX, Ataxia telangiectasia and Rad3 related and BRCA1.-Further reading:...
gene leading to defective mismatch repair
DNA mismatch repair
DNA mismatch repair is a system for recognizing and repairing erroneous insertion, deletion and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage....
, but displays no symptoms of "accelerated aging". Some DNA repair defects manifest as neurodegeneration
Neurodegeneration
Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. As research progresses, many...
rather than as cancer or
"accelerated aging".
Debate concerning "accelerated aging"
Some biogerontologists question that such a thing as "accelerated aging" actually exists, at least partly on the grounds that all of the so-called accelerated aging diseases are segmental progerias. Many disease conditions such as diabetes, high blood pressureHypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, etc. are associated with increased mortality
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
. Without reliable biomarkers
Biomarker (medicine)
In medicine, a biomarker is a term often used to refer to a protein measured in blood whose concentration reflects the severity or presence of some disease state...
of aging it is hard to support the claim that a disease condition represents more than accelerated mortality.
Against this position other biogerontologists argue that premature aging phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
s are identifiable symptoms associated with mechanisms of molecular damage. The fact that these phenotypes are widely recognized justifies classification of the relevant diseases as "accelerated aging". Such conditions, it is argued, are readily distinguishable from genetic disease
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s associated with increased mortality, but not associated with an aging phenotype, such as cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
and sickle cell anemia
Sickle-cell disease
Sickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...
. It is further argued that segmental aging phenotype is a natural part of aging insofar as genetic variation leads to some people being more disposed than others to aging-associated diseases
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...
such as 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...
and 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...
.