Progeroid syndromes
Progeroid syndromes (PS) are a group of rare genetic disorders that mimic physiological aging, making affected individuals appear to be older than they are.
The accumulated damage may arise from reactive oxygen species (ROS), chemical reactions (e.g. with intercalating agents), radiation, depurination, and deamination.
[3][13] Affected individuals can exhibit growth retardation, short stature, premature graying of hair, hair loss, wrinkling, prematurely aged faces, beaked noses, skin atrophy (wasting away) with scleroderma-like lesions, loss of fat tissues, abnormal fat deposition leading to thin legs and arms, and severe ulcerations around the Achilles tendon and malleoli.
Other signs include change in voice, making it weak, hoarse, or high-pitched; atrophy of gonads, leading to reduced fertility; bilateral cataracts (clouding of lens); premature arteriosclerosis (thickening and loss of elasticity of arteries); calcinosis (calcium deposits in blood vessels); atherosclerosis (blockage of blood vessels); type 2 diabetes; loss of bone mass; telangiectasia; and malignancies.
[11] Apart from causing defects in DNA repair, its aberrant association with p53 down-regulates the function of p53, leading to a reduction in p53-dependent apoptosis and increase the survival of these dysfunctional cells.
[citation needed] There is no evidence from the Bloom's Syndrome Registry or from the peer-reviewed medical literature that BS is a progeroid condition associated with advanced aging.
Unfortunately, the average lifespan of persons with Bloom syndrome is 27 years; consequently, there is insufficient information to completely rule out the possibility that BS is associated with some features of aging.
[22] Individuals with BS are characterized by low weight and height and abnormal facial features, particularly a long, narrow face with a small lower jaw, a large nose and prominent ears.
[23] Other characteristics of BS include learning disabilities, an increased risk of diabetes, gastroesophageal reflux (GER), and chronic obstructive pulmonary disease (COPD).
[citation needed] BS is caused by mutations in the BLM gene, which encodes for the Bloom syndrome protein, a RecQ helicase.
[27] Such defective recombination can introduce gaps and breaks within the genome and disrupt the function of genes, possibly causing growth retardation, aging and elevated risk of cancer.
It introduces gaps and breaks within the genome and disrupts the function of genes, often causing retardation of growth, aging and elevated risks of cancers.
Type II Cockayne syndrome (CSB) is more severe: symptoms present at birth and individuals live to approximately 6–7 years of age.
[3] Type III has the mildest symptoms, first presents later in childhood,[41] and the cause of death is often severe nervous system deterioration and respiratory tract infections.
[41] Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder, affecting about one per million in the United States and autochthonic Europe populations[40] but with a higher incidence rate in Japan, North Africa, and the Middle East.
Around 30% of affected individuals also develop neurological abnormalities, including deafness, poor coordination, decreased intellectual abilities, difficulty swallowing and talking, and seizures; these effects tend to become progressively worse over time.
[citation needed] Trichothiodystrophy (TTD) is a rare autosomal recessive disease whose symptoms span across multiple systems[56] and can vary greatly in severity.
[62] The function of the gene product of TTDN1 is unknown, but the sex organs of individuals with this form of TTD often produce no hormones, a condition known as hypogonadism.
[citation needed] Hutchinson–Gilford progeria syndrome is an extremely rare developmental autosomal dominant condition, characterized by premature and accelerated aging (~7 times the normal rate)[65] beginning at childhood.
[68] Individuals with HGPS typically appear normal at birth, but their growth is severely retarded, resulting in short stature, a very low body weight and delayed tooth eruption.
Other features include skeletal alterations (osteolysis, osteoporosis), amyotrophy (wasting of muscle), lipodystrophy and skin atrophy (loss of subcutaneous tissue and fat) with sclerodermatous focal lesions, severe atherosclerosis and prominent scalp veins.
[70] After being translated, a farnesol is added to prelamin A using protein farnesyltransferase; this farnesylation is important in targeting lamin to the nuclear envelope, where it maintains its integrity.
[citation needed] Restrictive dermopathy (RD), also called tight skin contracture syndrome, is a rare, lethal autosomal recessive perinatal genodermatosis.
[79] Individuals with RD exhibit growth retardation starting in the uterus, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, abnormal facial features (small mouth, small pinched nose and micrognathia), sparse or absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia and multiple joint contractures.
[86][87] Although the patients with these syndromes and the animal models with premature aging symptoms have different genetic backgrounds, they all have abnormal structures of tissues/organs as a result of defective development.
[93] Affected individuals exhibit intrauterine and postnatal growth retardation, leading to short stature and an aged appearance from birth.
They have physical abnormalities including a large head (macrocephaly), sparse hair, prominent scalp veins, inward-folded eyelids, widened anterior fontanelles, hollow cheeks (malar hypoplasia), general loss of fat tissues under the skin, delayed tooth eruption, abnormal hair pattern, beaked noses, mild to severe intellectual disability and dysmorphism.
[95] Within animal models for progeroid syndromes, early observations have detected abnormalities within overall mitochondrial function,[96][97] signal transduction between membrane receptors,[98] and nuclear regulatory proteins.
[104] F. Scott Fitzgerald's 1922 short story The Curious Case of Benjamin Button is about a boy who was born with the appearance of a 70-year-old and who ages backwards.
[106] Christopher Snow, the main character in Dean Koontz's Moonlight Bay Trilogy, has xeroderma pigmentosum, as does Luke from the 2002 novel Going Out by Scarlett Thomas.
