|WRN mutation ||Mutation in WRN causes Werner Syndrome which characteristics includes prematurely aged facies, scleroderma-like skin changes, cataracts, arteriosclerosis, subcutaneous calcification, and diabetes mellitus [McKusick et al. 1963; 5327241]. Inheritance is autosomal recessive and malignancy is frequent. THe frequency is 3 per million individuals in Japan .
Cells from a Werner heterozygote exit the cell cycle at a faster rate than do normal cells . Loss of WRN promoter aberrant mitotic recombination . ||Human ||— ||— ||— |
|UCHL1 mutation ||UCHL1 is assoicated with Parkinson's disease . UCHL1 belongs to a family of de-ubiquitinating enzymes responsible for the hydrolysis of bonds between ubiquitin molecules and small adducts . Decreased activity due to mutation may result in decreased labeling of abnormal proteins for clearance. ||Human ||— ||— ||— |
|PSEN1 mutation ||Mutations (more than 60 different) in PSEN1 are associated with Alzheimer's disease, of which all result in increased production of abnormally long amyloid beta-protein and an increase in senile plaque formation . ||Human ||— ||— ||— |
|MORF4 overxpression ||Overexpression of MORF4 reverses the immortal phenotype of immortal cell lines in complementation group B . Cellular senescence is dominant over immortality in fused hybrids of normal and immortal human cell in culture . Fusion of immortal cell lines with each other led to the idenetification of four complementation groups for immortality . MORF4 rescues the immortal phenotype . ||Human ||— ||— ||— |
|LMNA mutation ||Dominant mutation in LMNA (lamin A/C) gene cause Hutchinson-Gilford progeria syndrome (HGPS) which is rare and characterized by prematurly senile appearing skin and hair, with death from coronary artery disease often by age 10 [Gilford 1904; Hutchinson 1886; OMIM]. The median age of death in HGPS individuals is 13.4 years. A C to T transition at nucleotide 1824 is associated with HGPS [Sandra-Giovannoli et al., 2003; Eriksson et al., 2003]. The 1824C-T allele appears to act in a dominant negative manner by interfering with normal splicing, resulting in production of both the normal transcript and a transcript deleted for 150 bp at the 3' end [Sandre-Giovannoli et al, 2003]. Cultured skin fibroblasts from individuals with progeria exhibit an increased fraction of hat-labile proteins .
Gilford (1904). Ateleiosis and progeria: continuous youth and premature old age. Brit Med J 2, 914-918.
Hutchinson, J. (1886). Case of congenital absence of hair, with atrophic condition of the skin and its appendages, in a boy whose mother had been almost wholly bald from alopecia areata from the age of six. Lancet 1, 923. ||Human ||— ||— ||— |
|TERT overexpression ||Telomerase-expressing cells (human foreskin fibroblasts, retinal pigment epithelial cells) maintain normal length of telomeres and continue to divide vigorously . Cells expression telomerase have reduced staining for beta-galactosidase (a biomarker of cellular senescence) . TERT expression is also able to prevent the accelerated replicative senescence observed in cells taken from Werner's patients . ||Human ||— ||— ||— |
|HSPA9 overexpression ||Overexpression of HSPA9 (mortalin) increases the proliferation potential of normal fibroblasts . Transfection of normal human fibroblasts with human HSPA9 (or the murine Hspa9) overexpression vectors led to an increase in the number of population doublings the cells could sustain before senescing (increase varying from 32-60%, depending on the exact construct used). Transfected cells retain a youthful morphology longer than the controls cells, and there is an dealy in appearance of senescence associated beta-galactosidase activity . Mot-2 overexpressing cells exhibit a reduction in p53 transcriptional activation (as measured by expression from vectors containing either luciferase or beta-glactosidase driven by p53 binding sites) , which might partially or wholly explain the effects of Mot-2 on proliferative potential. HSPA9 is differentially distributed and/or translated in normal vs. transformed cells . ||Human ||— ||— ||— |
|Homozygous GH1 deletion ||Mean lifespan in untreated, affected individuals homozyogus for a deletion at the GH1 locus is significantly shorter (P < 0.05) than in affected siblings or the general population. Individuals homozygous for GH1 deletion demonstrate hereditary dwarfism . ||Human ||— ||— ||— |
|Down syndrom ||Individuals with Down syndrome develop the neuropathological lesions of Alzheimer disease significantly earlier than those without  and have a shorter lifespan. Down syndrome is cuased by duplication of small regions of chromosome 21 . The major features of Down syndrome are mental retardation, characteristic facial features, congenital malformations of the heart and gastrointestinal tract, thyroid disease, and an increased incidence of leukaemia [Epstein, 1989]. Neurons cultured in vivo form individuals with Down syndrome degenerate and exhibit apoptosis . Down syndrome neurons also display increased generation of reactive oxygen species and treatment with antioxidants can prevent degeneration. ||Human ||— ||— ||— |
|ERCC8 mutation ||Individuals with a mutation in ERCC8 (alias CKN1) have a shortened lifespan, short stature, precociously senile appearance, retinal degeneration, optic atrophy, sensitivity to sunlight, and mental retardation . Hypertension and renal disease are also common in ERCC8 mutants . ||Human ||— ||— ||— |
|BLM mutation ||BLM mutation cuases Bloom syndrom. Individuals with Bloom syndrome have a shortend life expectancy . Death is primary due to cancer, particulary leukemia and lymphoma [German, 1992]. Bloom syndrome is not a premature aging disease. Bloom syndrome characteristics are grwoth deficiency, sun-snesitivity, telangiectatic hypo- and hyperpigmented skin, predisposition to malignancy, and chromosomal instability . ||Human ||— ||— ||— |
|ATM mutation ||Individuals with ataxia-telangiectasia (AT) have a decreased lifespan, with a maximum of 52 years . ||Human ||— ||— ||— |