Progeroid syndromes are a group of diseases that cause individuals to age faster than usual, leading to them appearing older than they actually are.

Limited growth, full-body alopecia (hair loss), and a distinctive appearance (a small face with a shallow, recessed jaw and a pinched nose) are all characteristics of progeria.

Later, the condition causes wrinkled skin, kidney failure, loss of eyesight, and atherosclerosis and other cardiovascular problems.

Musculoskeletal degeneration causes loss of body fat and muscle, stiff joints, hip dislocations, and other symptoms generally absent in the non-elderly population.

[8] Its occurrence is usually the result of a sporadic germline mutation; although HGPS is genetically dominant, people rarely live long enough to have children, preventing them from passing the disorder on in a hereditary manner.

Once in the nucleus, the protein is cleaved by a protease called zinc metallopeptidase STE24 (ZMPSTE24), which removes the last 15 amino acids, which includes the farnesylated cysteine.

In 2003, the cause of progeria was discovered to be a point mutation in position 1824 of the LMNA gene, which replaces a cytosine with thymine.

[19] This mutation creates a 5' cryptic splice site within exon 11, resulting in a shorter than normal mRNA transcript.

Farnesylated prelamin A variants also lead to defective DNA repair, which may play a role in the development of progeria.

[29] Progerin may also play a role in normal human aging, since its production is activated in typical senescent cells.

[32] A subset of progeria patients with heterozygous mutations of LMNA have presented an atypical form of the condition, with initial symptoms not developing until late childhood or early adolescence.

[33] The general phenotype of atypical cases is consistent with typical progeria, but other factors (severity, onset, and lifespan) vary in presentation.

[citation needed] Prelamin A contains a CAAX box at the C-terminus of the protein (where C is a cysteine and A is any aliphatic amino acids).

After prelamin A has been localized to the cell nuclear membrane, the C-terminal amino acids, including the farnesylated cysteine, are cleaved off by a specific protease.

Although, the explanation for this defective-mitochondria accumulation in progeria is about to be elucidated, it has been proposed that low PGC1-α expression[42][43][45] (important for mitochondrial biogenesis, maintenance and function) along with low LAMP2 protein level and lysosome number (both important for mitophagy: the degradation of defective mitochondria pathway),[42] could be implicated.

Common side effects of the drug include "nausea, vomiting, diarrhea, infections, decreased appetite, and fatigue".

[13] Other treatment options have focused on reducing complications (such as cardiovascular disease) with coronary artery bypass surgery and low-dose acetylsalicylic acid.

[55] In studies on the cells another anti-cancer drug, rapamycin, caused removal of progerin from the nuclear membrane through autophagy.

Lonafarnib is an FTI, which means it can avoid this link, so progerin can not remain attached to the nucleus rim, and it now has a more normal state.

[citation needed] Studies of sirolimus, an mTOR Inhibitor, demonstrate that it can minimize the phenotypic effects of progeria fibroblasts.

[57] Moreover, the inhibition of CRM1 in HGPS alleviates the associated-senescence phenotype[57] as well as the mitochondrial function (an important determinant in senescence) and lysosome content.

[75] Repair of DNA double-strand breaks can occur by either of two processes, non-homologous end joining (NHEJ) or homologous recombination (HR).

A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in NHEJ and HR.

[84][failed verification] In 1987, fifteen-year-old Mickey Hays, who had progeria, appeared along with Jack Elam in the documentary I Am Not a Freak.

[87] Margaret Casey, a 29-year-old woman with progeria who was then believed to be the oldest survivor of the premature aging disease, died on Sunday, May 26, 1985.

Casey, a freelance artist, was admitted to Yale-New Haven Hospital on the night of May 25 with respiratory problems, which caused her death.

[90] Leon Botha, the South African painter and DJ who was known, among other things, for his work with the hip-hop duo Die Antwoord, lived with progeria.

[93][94] Adalia Rose Williams, born December 10, 2006, was an American girl with progeria, who was a notable YouTuber and vlogger who shared her everyday life on social media.

[96] Sister of American automobile designer, artist, and TV star, Chip Foose, who started a foundation in her name called Amy's Depot.

[98] Sammy Basso, born December 1, 1995, was an Italian biologist, activist and writer who studied progeria and campaigned to raise awareness of the disease, died at the age of 28 on October 5, 2024.