Premature aging syndrome

Progeroid syndromes (PS) are a group of rare genetic disorders which mimic physiological aging, making affected individuals appear to be older than they are. The term progeroid syndrome does not necessarily imply progeria (Hutchinson–Gilford progeria syndrome), which is a specific type of progeroid syndrome. Progeroid syndromes (PS) are a group of rare genetic disorders which mimic physiological aging, making affected individuals appear to be older than they are. The term progeroid syndrome does not necessarily imply progeria (Hutchinson–Gilford progeria syndrome), which is a specific type of progeroid syndrome. Progeroid means 'resembling premature aging', a definition that can apply to a broad range of diseases. Familial Alzheimer's disease and familial Parkinson's disease are two well-known accelerated-aging diseases that are more frequent in older individuals. They affect only one tissue and can be classified as unimodal progeroid syndromes. Segmental progeria, which is more frequently associated with the term progeroid syndrome, tends to affect multiple or all tissues while causing affected individuals to exhibit only some of the features associated with aging. All disorders within this group are thought to be monogenic, meaning they arise from mutations of a single gene. Most known PS are due to genetic mutations that lead to either defects in the DNA repair mechanism or defects in lamin A/C. Examples of PS include Werner syndrome (WS), Bloom syndrome (BS), Rothmund–Thomson syndrome (RTS), Cockayne syndrome (CS), xeroderma pigmentosum (XP), trichothiodystrophy (TTD), combined xeroderma pigmentosum-Cockayne syndrome (XP-CS), restrictive dermopathy (RD), and Hutchinson–Gilford progeria syndrome (HGPS). Individuals with these disorders tend to have a reduced lifespan. Progeroid syndromes have been widely studied in the fields of aging, regeneration, stem cells, and cancer. The most widely studied of the progeroid syndromes are Werner syndrome and Hutchinson–Gilford progeria, as they are seen to most resemble natural aging. One of the main causes of progeroid syndromes is genetic mutations, which lead to defects in the cellular processes which repair DNA. The DNA damage theory of aging proposes that aging is a consequence of the accumulation of naturally occurring DNA damages. The accumulated damage may arise from reactive oxygen species (ROS), chemical reactions (e.g. with intercalating agents), radiation, depurination, and deamination. Mutations in three classes of DNA repair proteins, RecQ protein-like helicases (RECQLs), nucleotide excision repair (NER) proteins, and nuclear envelope proteins LMNA (lamins) have been associated with the following progeroid syndromes: RecQ is a family of conserved ATP-dependent helicases required for repairing DNA and preventing deleterious recombination and genomic instability. DNA helicases are enzymes that bind to double-stranded DNA and temporarily separate them. This unwinding is required in replication of the genome during mitosis, but in the context of PS, it is a required step in repairing damaged DNA. Thus, DNA helicases, such as RecQ, maintain the integrity of a cell, and defects in these helicases are linked to an increased predisposition to cancer and aging phenotypes. Thus, individuals with RecQ-associated PS show an increased risk of developing cancer, which is caused by genomic instability and increased rates of mutation. There are five genes encoding RecQ in humans (RECQ1-5), and defects in RECQL2/WRN, RECQL3/BLM and RECQL4 lead to Werner syndrome (WS), Bloom syndrome (BS), and Rothmund–Thomson syndrome (RTS), respectively. On the cellular level, cells of affected individuals exhibit chromosomal abnormalities, genomic instability, and sensitivity to mutagens. Werner syndrome (WS) is a rare autosomal recessive disorder. It has a global incidence rate of less than 1 in 100,000 live births, although incidences in Japan and Sardinia are higher, where it affects 1 in 20,000-40,000 and 1 in 50,000, respectively. As of 2006, there were approximately 1,300 reported cases of WS worldwide. Affected individuals typically grow and develop normally until puberty, when they do not experience the typical adolescent growth spurt. The mean age of diagnosis is twenty-four. The median and mean age of death are 47-48 and 54 years, respectively; the main cause of death is cardiovascular disease or cancer.