Thus, individuals with RecQ-associated PS show an increased risk of developing cancer, which is caused by genomic instability and increased rates of mutation. 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. 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. DNA helicases are enzymes that bind to double-stranded DNA and temporarily separate them. RecQ is a family of conserved ATP-dependent helicases required for repairing DNA and preventing deleterious recombination and genomic instability. 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: įurther information on RecQ: RecQ helicase and Helicase with intercalating agents), radiation, depurination, and deamination. The accumulated damage may arise from reactive oxygen species (ROS), chemical reactions (e.g. The DNA damage theory of aging proposes that aging is a consequence of the accumulation of naturally occurring DNA damages. One of the main causes of progeroid syndromes is genetic mutations, which lead to defects in the cellular processes which repair DNA. The most widely studied of the progeroid syndromes are Werner syndrome and Hutchinson–Gilford progeria, as they are seen to most resemble natural aging. Progeroid syndromes have been widely studied in the fields of aging, regeneration, stem cells, and cancer. Individuals with these disorders tend to have a reduced lifespan. Most known PS are due to genetic mutations that lead to either defects in the DNA repair mechanism or defects in lamin A/C.Įxamples 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). 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.Īll disorders within this group are thought to be monogenic, meaning they arise from mutations of a single gene. They affect only one tissue and can be classified as unimodal progeroid syndromes. Familial Alzheimer's disease and familial Parkinson's disease are two well-known accelerated-aging diseases that are more frequent in older individuals. Progeroid means "resembling premature aging," a definition that can apply to a broad range of diseases. 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 that mimic physiological aging, making affected individuals appear to be older than they are.
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