Review on Progeria: A Rare Genetic Premature Aging Disorder


Rupa Bhattacharya, Samira R. Khan

Maharashtra Institute Of Pharmacy (B.Pharm) Betala, Bramhapuri

*Corresponding Author E-mail:,




Progeria also known as “Hutchinson Gilford Progeria Syndrome”, was reported by Jonathan Hutchinson in 1886 and further described by “Hasting Gilford” in 1904. It is rare genetic disorder characterized by dramatic phenotype premature  aging and accelerated cardiovascular disease.It is mostly caused by a de novo point mutation in the lamin A gene that activate a cryptic slice donor site ,producing a truncated mutant protein termed “progerin”.Clinical manifestations are evident by the first and second year of solely on physical symptoms but today the progeria research foundation has established progeria cell and tissue banks to assist in further diagnostic process.Treatment include aspirin which helps prevent the atherithrombotic events ,stroke and heart attack by hindering platelet aggregation.


KEYWORDS: Phynotype Premature Aging, hindering platelet aggregation, atherithrombotic events.





The term Progeriais derived from the Greek word ‘pro’ meaning early and ‘geros’ meaning old age.[2] “Hutchinson- Gilford Progeria Syndrome” (HGPS) belong to a group of conditions called laminopathies which affect nuclear lamin. Mutation takes place during the early stages of embryo development in two genes LMNA and ZMPSTE.The disorder never passed on from affected parent to child. HGPS has a low incidence and most of these children hardly survive before they step into adolescent age.The maximum survival chances are not more than 13 years; although many have been known to live upto their teens and early twenties and rare individuals may even reach their forties.[1] The disease causes the balding, loss of eyebrows and eyelashes in frist few years. Widespread loss of subcutaneous tissue occurs. The skin appears old and pigmented age spots.The person are very short and thin.


These syndromes include clinically and genetically heterogeneous disease such as Bloom syndrome, Cockayne syndrome, Fanconi anaemia, Rothmund-Thomson syndrome, and Werner syndrome (also known to be adult progeria).[1][2]



The world “Progeria” means “prema turely old” in Hutchinson-Gilford progeria is caused by a tiny mutation in a single gene, known as lamin A (LMNA). In laboratory tests involving cells taken from progeria patients, researchers found that the mutation responsible for Hutchinson-Gilford progeria causes Greek. Named after the scientists who discovered it, Dr. Hutchinson in 1886 and Dr.hasting Gilford in 1904.


Major researchers of Progeria:

Dr. Francis Collins.who discovered the gene.

Doctors at the national Human Genome Reseacher Institute (NHGRI).

Dr. Hutchinson and Dr. Gilford the LMNA gene to produce an abnormal form of the lamin A protein which destabilizes the patient’s cells.



Thirty years ago, virtually nothing was known about progeria, and due to the rarity of the disease, little research was done until the 1990s.


Progeria is an extremely rare genetic disease of childhood characterized by dramatic, premature aging. The condition is estimated to affect one in 8 million newborns worldwide. Hutchinson-Gilford progeria syndrome (HGPS) is the most severe form of the disease.


As newborns, children with progeria usually appear normal. However, within a year, their growth rate slows and they soon are much shorter and weigh much less than others their age. While possessing normal intelligence, affected children develop a distinctive appearance characterized by baldness, aged-looking skin, a pinched nose, and a small face and jaw relative to head size. They also often suffer from symptoms typically seen in much older people: stiffness of joints, hip dislocations and severe, progressive cardiovascular disease.


Some children with progeria undergo coronary artery bypass surgery and/or angioplasty in attempts to ease the life- threatening cardiovascular complications caused by progressive atherosclerosis.


Death occurs on average at age 13, usually from heart attack or stroke.



In 2003, NIH-funded researchers discovered that A genetic test for Hutchinson-Gilford progeria syndrome is currently available. In the past, doctors had to base a diagnosis of progeria solely on physical symptoms, such as skin changes and a failure to gain weight, that were not fully apparent until a child's first or second year of life.


A mouse model of progeria has been developed that is helping scientists test experimental therapies for progeria and also explore cardiovascular disease in general.

Researchers have published cell culture and mouse model studies that support a potential drug treatment for children with Progeria. Farnesyltransferase inhibitors (FTIs), originally developed for cancer, are capable of reversing the dramatic cell structure abnormalities that are the hallmark of cells from children with Progeria.


Clinicians in the Intramural Office of Rare Disease have completed a comprehensive analysis of the natural history of progeria over a 15-month period in 15 children between the ages of 1 and 17 years in order fully characterize the disease and gain insight into its progression. An initial 2-year trial using FTI therapy has been completed and the results are being analyzed.


A second clinical trial has been initiated using previously approved drugs, Statins, which lower cholesterol levels and Zometa (zolendronic acid), a treatment for bone diseases, in a triple drug combinatorial therapy.


NIH researchers have published a comparison between cardiovascular disease pathology in progeria patients versus typical cardiovascular disease in normal aging and have found many aspects in common. Although not found at the same levels as in HGPS patients, progerin protein is detectable in very small amounts in younger normal subjects and the protein expression increases with age.


Researchers at NIH continue to explore additional potential therapeutics for the treatment of progeria using the next generation mouse model for HGPS.



The NIH is poised to make major advances in the treatment of progeria, as well as in the fields of aging and heart disease.


NIH-funded researchers are exploring the possible role of the wild-type LMNA gene in the aging process. They are collecting and analyzing DNA from a cohort of about 600 centenarians to determine whether there is something unique about their LMNA gene sequence that promotes longevity.


Research studies on progeria have examined the damage caused by the mutant lamin A protein on blood vessel cells in humans and mice. These discoveries offer increased hope for a cure for progeria and may also provide key insight into the cause of adult heart disease.



HGPS is rare disorder prevalent in 1 in 4-8 million newborns.Incidence of progeria is uniform throughout the world showing no gender, geographical or ethnic predisposition, and hence considered to be sporadic.Presently,there are 114 children across 39 countries diagnosed with HGPS.[6][41] The average age of survival is 13 years and death occur due to stroke, myocardial infration or atherosclerosis.


Classical HGPS is usually cause by sporadic autosomal dominant mutation taking place during the early stages of embryo development. There are a few atypical forms of progeria, also called as non-classical progeria and follows autosomal recessive pattern of inheritance.[7][42]

The disease causes the balding, loss of eyebrows and eyelashes in frist few years. Widespread loss of subcutaneous tissue occurs. The skin appears old and pigmented age spots. The person are very short and thin. The syndrome shows =100 cm of height, but the usually weigh < 12-15 kg even as teenagers. The voice is thin and high pitched. The syndrome is characterized by the facial appearance with prominent eyes, a beaked nose, a plucked-bird appearance smaal jaw and large cranium. The bones shows distinctive changes, with frequent resorption of clavicles and replacement by fibrous tissue. Resorption      of           the          terminal finger bones (acroosteolysis), stiffening of finger joints elbow and knee joint enlargementand resulting “horse-riding”. These syndromes include clinically and genetically heterogeneous disease such as Bloom syndrome, Cockayne syndrome, Fanconi anaemia, Rothmund-Thomson syndrome, and Werner syndrome (also known to be adult progeria). [60]


There have been only two known cases in which it became evident that a healthy person can carry the LMNA mutation that causes progeria. These carriers were identified because they passed it on to their children. One family from India has five children with progeria, although this is not a classical HGPS; they were the subject of a 2005 Bodyshock documentary entitled The 80 Year Old Children, while another from Belgium has two.



Hutchinson-Gilford Progeria Syndrome develops a characteristic facial appearance including prominent eyes,a thin nose with a beaked tip,a small chin ,and protruding ears.It also cause hair loss(alopecia),ages looking skin, joint abnormalities and loss of fat under skin.[7] This condition does not disrupt intellectual development or the development of motor skill such as sitting ,standing,and walking.[8]


Symptoms of HGPS based on various parameters of health are enlisted below:



Short stature and stunted growth

Weight distinctly low for height

Head disproportional large for face

Body fat:

Diminished subcutaneous fat

Prominent scalp vein




Skeletal system:

Distal phalangeal osteolysis

Pear shaped thorax


Horse riding stance

Thin limds

Tightened joint ligament



Severe, progressive atherosclerosis with widely variable age of clinical manifestation



Thin, dry, wrinkled skin,

Sclerodermatous skin

Loss of eyelashes

Dystrophic nails



Progeria patient the lenght of telomeresand rapidity of aging.The repaeating sequences of TTAGGG that cap each chromosomes decreases in lenght after each replication.progeria patient has shorttelomere.In 2003 there was 90% of progeria affected children which has a mutation inposition 1824 of LMNA gene,replacing cytosine with thymine, creating an unustable form of protein Lamin A. Lamin A is a building block of nuclear envelope which is developed in cell division or in the gametes.Nuclear Lamin A is a protein scaffold on the inne edge of nulcear that helps for the synthesis of RNA and DNA.


Table 1: Comparison between a normal cell and a progeria cell.

Steps in Normal Cell

Steps in Progeria Cell

The gene LMNA encodes a protein called prelamin A

The gene LMNA encodes a protein called prelamin A

Prelamin A has a farnesyl group

attached to its end

Prelamin A has a farnesyl group

attached to its end

Farnesyl group is removed from prelamin A

Farnesyl group remains attached to prelamin A

Normal form called PRELAMIN A

Abnormal form of prelamin A


Prelamin A is not anchored to the nuclear rim

Progerin is anchored to the nuclear rim

Normal state of the nucleus

Abnormally shaped nucleus.


Prelamin A contains a CAAX box at the C terminus of protein (where C is a cysteine and A is any aliphatic amino acid).The cysteine is farnesylated and allows prolaminA to bind to membrane,after this prolamin A is located to cell nuclear membrane.THe C-terminal amino acid,including the farnesylated cysteine are cleaved off by specific protease.In HGPS, the recognition site that the enzyme requires for cleavage of prelamin A to lamin A ismutated.Lamin A cannot be produced, and prelamin A buildsup on the nuclear membrane, causing a characteristic nuclear blebbing. [10] This results in the premature agingsymptoms of progeria.


A study that compared HGPS patient cells with theskin cells from




Fig.  Normal Cell and HGPS Cell.


LMNA young and elderly humansubjects found similar defects in the HGPS and elderlycells, including down-regulation of certain nuclearproteins, increased DNA damage, and demethylation of histone, leading to reduced heterochromatin.[11] Nematodes over their lifespan show progressive lamin changes comparable to HGPS in all cells but neuronsand gametes. [12]


LMNA gene

A-type and B-type lamins (Type V intermediate filaments) are the main components of thenuclear lamina, the innermost layer of the nuclear envelope. The nuclear lamina in mammalian cell is a thin (20–50 nm) protein meshwork that interacts with various proteins and chromatin and isessential for maintaining the structural integrityof the nuclear envelope, the protective barrierbetween the cytoplasm and nucleus.[12] The A-type lamins are encoded by LMNA (MIM150330), which spans 57.6 kb of genomic DNA.By alternative splicing of its 12 exons, four proteins are created: two minor products: laminAD10 and lamin C2; two major products: lamina and lamin C. Lamin A is coded by exons1–12 and lamin C is derived from LMNA by use ofan alternative splice site in intron. Thus, lamin C differs at the Cterminal from lamin A, since itlacks the final part of exon 10, as well as exons 11and 12. Lamin A, a 664 amino acid proteinwith a molecular weight of 70 kDa, is normallysynthesized as a precursor molecule, called prelaminA. It contains a CAAX-box motif at the C terminus, which is subject to farnesylation. After farnesylation, an internal proteolytic cleavageoccurs, removing the last 18 coding aminoacids to generate mature lamin A.[13] Lamin C isslightly smaller with a length of 574 amino acid sand a weight of 65 kDa. Together, the two proteinsform heterodimers through their roddomains, to create the filamentous structures found in the nuclear lamina.[14]


Molecular diagnosis

As most cases of HGPS appear to be due to a de novo mutation in the same codon (G608G), screening for this mutation is certainly theoretically feasible, especially with the decreasing cost of genomic DNA analysis. However, due to the sporadic nature of the phenotype, predictive screening is not practical at present, since there is no way to determine which children are at risk. Furthermore, the benefit is limited, considering that there is no present treatment for progeria. For the parents of a previously affected child, parental somatic mosaicism is a theoretical possibility. Concerns about the recurrence of HGPS in future pregnancies for such individuals might now be addressed through genetic testing. LMNA testing may also be valuable in making a molecular diagnosis in an individual affected with a suggestive phenotype, that is, to determine whether their disease was ‘classical’ HGPS or atypical progeroid. As mentioned above, a precise molecular diagnosis may be important, as future therapies may depend upon knowing the genetic basis of the phenotype.[15]


Clinical Diagnosis

Actually there is no clinically approved test to diagnose progeria up to date. Until 2003, in order todiagnose Progeria, doctors observed phenotype i.e. physical symptoms, such as skin changes and a failure to gain weight, which were not fully apparent until a child's first or second year of life, as well as x- rays of patients and urinary hyaluronic acid testing but had no definitive test.


Urinary hyaluronic acid testing

Chemical tests may reveal elevated levels of chemical hyaluronic acid in the urine as well as certain fatty compounds, and reduced levels of certain primary antioxidant enzymes in the blood. This may also increase likelihood of death, as one cause of aging is believed to be a buildup of oxidants in the blood over time.Although urinary hyaluronic acid has been reported to be increased in most children with HGPS the measurement is now regarded as unreliable and is not recommended for diagnosis.21 Now- a-days, with the discovery of the mutated Lamin A gene, blood samples and a skin biopsy taken from patients can be evaluated for presence of the mutated gene, this gives an definitive diagnosis.[16] Additionally,the Progeria Research Foundation has set up a new Diagnostic Program whose first goal is to establish a Progeria cell and tissue bank to assist in furtherresearch. Scientists are exploring possibilities of using existing drugs to block or reduce production ofthe abnormal Lamin A protein in children with Progeria.Today the only treatment for Progeria patients is administering a low dose of aspirin throughout their lives. Aspirin may help prevent atherothrombotic events, stroke and heart attacks by hindering platelet aggregation. Currently there is no cure for the disease.[17]


Prenatal Testing

Prenatal diagnosis for HGPS is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at bout 15-18 weeks'gestation or chorionic villussampling (CVS) at about 10-12 weeks' gestation. The disease-causing allele of an affected family member must be identified before prenatal testing.[18]


Because HGPS has thus far not been reported to recur in families, prenatal testing would only be performed because of the (unlikely) possibility of germlinemosaicism in one of the parents.


Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.


Pre implantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutation has been identified in an affected family member for laboratories offering PGD.[18]


Some other diagnosis

Low leves of high density lipoprotein (HDL) cholesterol, also called as good cholesterol, that keeps arteries open, that revealed in blood test but this is not diagnostic itself, in progeria.


Diagnosis can be done based on signs and symptoms, by blood tests revealing, low level of High-Density Lipoprotein (HDL), by conducting genetic tests.[19] Stroke or heart attack can be prevented, if the diagnosis is done earlier.


Exams and Tests

The health care provider will perform a physical exam and order laboratory tests. This may show:



Skin changes similar to that seen in scleroderma (the connective tissue becomes tough and hardened).


Fig. Diagnosis


Fig. HGPS diagnostic criteria’s TREATMENT


There is no cure for progeria. Treatment is aimed at controlling the devastating effects caused by premature aging. Prescribed formulas of antioxidants, vitamins, lipoic acid, and coenzyme-Q are used to increase antioxidant levels. Low antioxidant levels are common in persons with progeria and cause cellular destruction. Research is currently underway to use gene therapy to treat progeria.


Most treatment focuses on reducing complications (such as cardiovascular disease) with heart bypass surgery or low-dose aspirin. Children may also benefit from a highcalorie diet.


Children with Progeria need Physical Therapy (PT) and Occupational Therapy (OT) as often as possible (optimally 2-3 times each per week) to ensure maximum range of motion and optimal daily functioning throughout their lives.[37]

Growth hormone treatment has been attempted.


A type of anticancer drug, the farnesyltransferase inhibitors (FTIs), has been proposed, but their use has been mostly limited to animal models. A Phase II clinical trial using the FTI lonafarnib began in May 2007. In studies on the cells another anti-cancer drug, rapamycin, caused removal of progerin from the nuclear membrane through autophagy. It has been proved that pravastatin and zoledronate are effective drugs when it comes to the blocking of farnesyl group production. However, it is important to bear in mind that no treatment is able to cure progeria nowadays.[38]


Fig: Points where pharmacs used to inhibit progerin farnesylation act.


Farnsyl transferase inhibitors (FTIs) are drugs which inhibit the activity of an enzyme needed in order to make a link between progerin proteins and farnesyl groups. This link generates the permanent attachment of the progerin to the nuclear rim.[39] In progeria, cellular damage can be appreciated because that attachment takes place and the nucleus is not in a normal state. Lonafarnib is an FTI, which means it can avoid this link, so progerin can not remain attached to the nucleus rim and it has now a more normal state. The delivery of Lonafarnib is not approved by the US Food and Drug Administration (FDA). Therefore, it can only be used in certain clinical trials.


Pravastatin is traded as Pravachol or Selektine and it is included in the family of statins. As well as zelodronate, its utilit]y in Hutchinson-Gilford progeria syndrome (HGPS) is the Clinical Trials Over HGPS Methods.




Prevention of farnesyl groups formation, which progerin needs to provoke the disease. Some animal trials have been realized using FTIs or a combination of pravastatin and zoledronate so as to observe whether they are capable of reversing abnormal nuclei. The results, obtained by blinded electron microscopic analysis and immunofluorescence microscopy, showed that nucleus abnormalities could be reversed in transgenic mice expressing progerin. The reversion was also observed in vivo -- cultured cells from human subjects with progeria -- due to the action of the pharmacs, which block protein prenylation (transfer of a farnesyl polypeptide to C-terminal cysteine). when it comes to the results, that: “The further suggest that skin biopsy may be useful to determine if protein farnesylation inhibitors are exerting effects in subjects with HGPS in clinical trials”. Unlike FTIs, pravastatin and zoledronate were approved by the U.S. FDA (in 2006 and 2001 respectively), although they are not sold as a treatment for progeria. Pravastatin is used to decrease cholesterol levels and zoledronate to prevent hypercalcaemia.


Rapamycin, also known as Sirolimus, is a macrolide. There are recent studies concerning rapamycin which conclude that it can minimize the phenotypic effects of progeria fibroblasts. Other observed consequences of its use are: abolishment of nuclear blebbing, degradation of progerin in affected cells and reduction of insoluble progerin aggregates formation. All these results do not come from any clinical trial, although it is believed that the treatment might benefit HGPS kids.


It should always be taken in account that no treatment is delivered in order to cure Hutchinson-Gilford progeria syndrome, for all of them are in pre-clinical stages.


General Participants were ≥2 years of age with clinically and genetically confirmed .Gly608Gly classic HGPS, adequate organ and marrow function, reliable pretrial body weights, and ability to travel for regular study visits. The study was approved by the Boston Children’s Hospital Committee on Clinical Investigation. Written informed consent was obtained, and when indicated, consents were translated into the parents’ primary language and discussions were performed with interpreters. Age-appropriate assent was also obtained. An initial feasibility study enrolled 5 participants who were naïve to lonafarnib therapy; participants received triple therapy and were observed for a period of 4 weeks for significant toxicities. Because no significant toxicities were observed, these participants were subsequently enrolled in a phase 2 study without treatment interruption, along with 32 additional participants.



Study Drug Dosing and Administration

Trial medications were administered for a period of 40 to 52 months. Lonafarnib dosing was continued or, for naïve participants, initiated at 150 mg/m2 twice daily. Participants experiencing drug-related grade 3 or 4 toxicity not responsive to supportive care measures were dose reduced to 115 mg/m2. Subsequently, participants were permitted to increase the dose of lonafarnib back to 150 mg/m2 and monitored for tolerance. Participants were prescribed oral lonafarnib by either capsule or liquid suspension dispersed in Ora-Blend SF or Ora-Plus every 12±2 hours. Oral pravastatin dosing was 5 mg for participants weighing 10 kg once every 24±2 hours. Zoledronic acid was administered intravenously over 30 minutes; at baseline; at months 6, 12, and 18; and at the end of therapy. The initial infusion was 0.0125 mg/kg body weight; all other infusions were 0.05 mg/kg body weight. Serum calcium was measured immediately after infusion and at 1 to 2 days after infusion. Oral calcium (500 mg) and vitamin D (1000 IU) were supplemented daily to avoid hypocalcemia and vitamin D deficiency. Calcium supplementation was discontinued after 12 months.


Toxicity Monitoring


Participants were monitored for liver, kidney, and hematologic toxicity at each trial visit and between visits when indicated symptomatically. Adverse events were monitored and recorded throughout the study during on-site visits, regularly scheduled home communications, and communications as a result of interim toxicities.


Lonafarnib, Pravastatin, and Zoledronic Acid Treatment Toxicity

Overall, therapy was well tolerated, and no participant came off study because of treatment-related toxicity.[56][58] Toxicity details were consistent with the known toxicity profiles of lonafarnib and zoledronic acid . Generally, lonafarnib-related side effects included mild diarrhea, fatigue, nausea, vomiting, anorexia, abdominal pain, and elevated liver function tests. No pravastatin-related side effects were identified. Zoledronic acid–related side effects included postinfusion flu-like symptoms and hypocalcemia, at rates significantly lower than those previously published for non-HGPS pediatric studies.[59] Within 48 hours of successive zoledronic acid infusions, participants developed ≥1 flu-like symptoms at rates of 11.1%,  25.7%,  14.3%,  2.9%, and 6.7%, respectively. Participants developed hypocalcemia at rates of 5.6%, 5.7%, 8.6%, 0%, and 3.3%, respectively. Overall, 23 of 37 participants (62%) experienced postinfusion side effects.


Case Report

A 14-year-old girl child presented with progressive history of coarsening of skin, failure to thrive and inability to squat for the past three to four years. The child had also developed global alopecia over the past few years. The perinatal history was uneventful. She was apparently normal till one year of age when the parents started noticing the above features. She had normal intelligence. No family history of similar complaints could be elicited.General examination revealed the child to be of short stature and malnourished. Eyes appeared prominent with hypoplastic chin. Multiple patches of coarse and thickened skin, especially over the dorsum of the hands and shoulders. The terminal ends of the fingers appeared broad and stubby. Based on the history and clinical findings a provisional diagnosis of progeria was made.


Biochemical investigations were normal except for increased serum cholesterol and increased urinary excretion of hyaluronic acid. To confirm the diagnosis, the child was subjected to a skeletal survey. Radiographs of the skull showed diastasis of the sagittal suture with numerous wormian bones [Figure]. Radiograph of the mandible showed the hypoplastic mandible with infantile angle [Figure]. Radiograph of the chest showed sloping ribbon-like ribs with thinning of both third ribs posteriorly. The lateral half of both the clavicles was absent [Figure]. Radiograph of the dorsal spine in the lateral projection showed presence of fish mouth vertebrae [Figure 4]. Pelvis radiograph in AP projection presence of bilateral coxa valga deformity [Figure]. Radiograph of the hands and feet revealed resorption of terminal phalanges [Figures]. The bone age however corresponded to the chronological age of the patient. The radiological findings confirmed the clinical diagnosis of progeria.


Fig. X-ray of the skull, AP (a) and Lateral (b) views showing multiple wormian bones, diastasis of the sagittal suture (a) and prominent vascular markings (b)


Fig. Lateral radiography of the mandible shows small mandible with small ascending ramus and infantile obtuse angle.


Fig. Radiograph of the chest shows absence of the lateral half of the clavicle and thin ribbon-like third rib on both side.


Fig. Focused lateral radiograph of the dorsal spine shows fishmouth vertebra.


Fig. Radiograph of both hips shows severe coxa valga.


Fig . Radiograoh of both hands shows acro-osteolysis.


Fig Radiograph of both feet shows acro-osteolysis 11.Scope for future research


Progeria (or HGPS) is a rare syndrome which makes it difficult to study. Due to the efforts of parents of the affected children, a few research groups and the Progeria Research Foundation (PRF), the awareness of this syndrome has increased significantly. Research has also proposed probable markers for this syndrome. For example, elevated HA levels have been suggested as specific marker for HGPS[46][48][49], but other studies have nullified this by reporting that urinary and serum levels of HA in HGPS patients are comparable with controls. Gordon and co-workers did a thorough analysis of the serum and urinary hyaluronidases by both quantitative (using ELISA) and qualitative (using a gel detection method) methods and contravened the use of HA as a marker for HGPS. Hence, the search for an accessible and definite kind of diagnostic marker is still on.


The role of GH/IGF-1 axis in determining longevity has long been known[51] .A study has shown that DNA damage results in suppression of the GH/ IGF-1 axis which in turn leads to remarkable progeroid symptoms[47.] More research on the causes and patterns of DNA damage in HGPS and ageing may provide some useful links between ageing and PS(s). The positive or negative interactions between the LMNA gene and other genes controlling ageing and longevity can be studied in appropriate animal models for better understanding of the pathogenesis and progression of HGPS. The PRF has 121 cell lines in their Cell and Tissue Bank, which are available on request for research purposes. A clear perception of the mechanism of pathogenesis of HGPS and other PSs would be helpful in understanding the abnormal conditions in the diverse branches of basic and applied life sciences like molecular biology, basic cellular senescence phenomenon, mitochondrial physiology, oncology, functional genomics and proteomics, dermatology especially dermal physiology, stem-cell biology, and many other degenerative disorders regarding which our knowledge is still meagre[52] .Thus, discovery of a cure for PS(s) would not only help the affected children but also a large number of patients suffering from cardiovascular diseases, stroke, cancer, etc.


Proteins linked to HGPS are suspected to play a pivotal role in the ageing process and this could be one of the reasons responsible for making these children predisposed to premature, progressive heart disease. When factors like IGF-1 signaling and functional cascade of events (of hormones) are checked in the prevalent and existing models of ageing and longevity (diet restriction), it has been observed that there is a significant shift from the normal parameters. This shift can be due to pituitary or any organ related faults, defect in the micronutrient (like vitamin D, etc.) metabolism, abnormal protein glycation, disturbed antioxidant status, to any other physiological process. It has been observed that WNIN/Ob (Wistar of National Institute of Nutrition obese rat) obese rats exhibits an unusual premature aging, develop various tumours, and have other immune response deficits[53][54][55] .These kinds of animal models should be checked for their genomic, proteomic and biochemical status to look into the details of the common or shared and probably faulty pathways.



Hutchinson Gilford Progeria Syndrome is a rare disease. Skin, bone, and cardiovascular structures are primarily involved. Skin and bone abnormalities account largely for a premature aged appearance, and cardiovascular changes account largely for death. Research has shown that progeria does not unequivocally parallel the normal aging process at an accelerated rate and that a connective tissue defect may possibly explain the syndrome. Elevated levels of a ground substance component, hyaluronic acid, which normally increases with advancing age, have been detected, but whether this elevation is of sole causal significance remains to be shown. Further inquiry is warranted to explain the fundamental determinants of this disorder fully. Despite being described in as early as 1886, it was not until this last decade that the precise cause of HGPS has been elucidated. Gene discovery paved the way for a greater understanding of HGPS, exploration of treatment options, as well as insight into the potential role of prelamin A in the general aging process.



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Received on 17.09.2019         Modified on 09.11.2019

Accepted on 27.12.2019     ©AandV Publications All right reserved

Res.  J. Pharmacology and Pharmacodynamics.2020; 12(2): 73-82.

DOI: 10.5958/2321-5836.2020.00015.4