Is Premature Aging Real?

Progeroid syndromes refer to a group of rare genetic disorders that causes premature aging.

Normal aging results in a progressive decline of the physiological systems over time, putting individuals at increased risk for chronic conditions. Although aging is a normal physiological process that affects all humans, patients with progeroid syndromes experience the process in a greatly accelerated manner, causing them to experience symptoms of advanced age during childhood and early adulthood.¹

Progeroid syndromes are classified into 2 groups based on the underlying pathway. The first group includes those caused by the defects in components of the nuclear envelope that affects chromatin organization and gene regulation. This includes atypical progeria syndromes, Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, Néstor-Guillermo progeria syndrome, and restrictive dermopathy. The second group is affected by defects in the process of DNA repair. The consequences of this defect are genomic instability and increased risk of developing cancer. Well-known examples in this group are Bloom syndrome, Cockayne syndrome, Rothmund-Thomson syndrome, and Werner syndrome.²

Hutchinson-Gilford progeria syndrome, also known as progeria, is the most prevalent and widely studied form of this disorder.² Progeria comes from the Greek word, geras, which means old age. This disorder was first described by English physician Jonathan Hutchinson in 1886 and then later by another English physician, Hastings Gilford in 1904.³

Individuals with this condition appear normal at birth but begin showing symptoms within their first year of life. The most prominent symptom at this stage is delayed physical growth. As the disorder progresses, the appearance of these children is characterized by features, such as a beaked nose, large eyes and head size, narrow face, and visible veins. Children also begin suffering from symptoms typically associated with old age, such as alopecia, hip dislocation, joint stiffness, loss of muscle mass, and wrinkled skin.³ A major health issue that most of these patients experience is progressive cardiovascular disease that often results in life-threatening complications, such as heart attacks and strokes. The average life expectancy of these patients is 13 years, primarily, because of these complications, though some patients with this disorder survive into their 20s.⁴

There are an estimated 200 to 250 children who live with progeria worldwide, with about 24 cases in Europe, 20 cases in North America, 18 cases in Asia, 16 cases in Central and South America, and 4 cases in Africa, according to the Progeria Research Foundation’s database.⁵

Recently the FDA approved lonafarnib (Zokinvy; Eiger Biopharmaceuticals) capsules to reduce the risk of death due to Hutchinson-Gilford syndrome. This drug has also been approved for the treatment of certain processing-deficient progeroid laminopathies in patients 1 year of age and older. Lonafarnib is a farnesyltransferase inhibitor that helps prevent the buildup of defective progerin or progerin-like protein. The most common adverse effects of the drug are decreased appetite, diarrhea, infection, nausea, and vomiting. This drug is also contraindicated for co-administration with moderate or strong CYP3A inducers and inhibitors, as well as midazolam and certain cholesterol-lowering medications.⁶

Regular monitoring for blood vessel disease is recommended for individuals with progeria. Patients’ height and weight are measured on a regular basis at physician appointments to track growth rate. Some therapies that may delay or reduce signs and symptoms of the disease include drugs to reduce blood pressure, low-dose aspirin, occupational and physical therapy to reduce joint stiffness, and statins to lower cholesterol. Nutrition with high-calorie foods and supplements can also help maintain adequate body mass for these patients. Dental problems for these patients are common, so visiting a dentist regularly is also recommended.⁷

There are also recommended home remedies and lifestyle modifications for individuals with progeria. Some of these include accessing support groups and networks to help cope with the disease and its complications, avoiding sun exposure and using sunscreen, frequent but small meals, hydration, immunization, and regular physical activity.⁷

Saro Arakelians, PharmD, is vice president of pharmacy operations at a pharmacy in the Los Angeles, California, area. Ngoctran Tran is a PharmD candidate at the University of Southern California School of Pharmacy in Los Angeles.

REFERENCES

• Schnabel F, Kornak U, Wollnik B. Premature aging disorders: a clinical and genetic compendium. Clinical Genetics. 2020. doi:10.1111/cge.13837
• Navarro CL, Cau P, Lévy N. Molecular bases of progeroid syndromes. Human Molecular Syndromes. 2006;15(2):151-161. doi:10.1093/hmg/ddl214
• National Institutes of Health. About progeria. National Human Genome Research Institute. Updated December 27, 2013. Accessed January 4, 2021. https://www.genome.gov/Genetic-Disorders/Progeria
• Mayo Clinic. Progeria overview. February 1, 2018. Accessed January 4, 2021. https://www.mayoclinic.org/diseases-conditions/progeria/symptoms-causes/syc-20356038
• Coppedè F. The epidemiology of premature aging and associated comorbidities. Clin Interv Aging. 2013;8:1023-1032. doi:10.2147/CIA.S37213
• FDA approves first treatment for Hutchinson-Gilford progeria syndrome and some progeroid laminopathies [news release]. November 20, 2020: FDA. Accessed January 4, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-hutchinson-gilford-progeria-syndrome-and-some-progeroid-laminopathies
• Mayo Clinic. Progeria diagnosis. February 1, 2018. Accessed January 4, 2020. https://www.mayoclinic.org/diseases-conditions/progeria/diagnosis-treatment/drc-20356043. https://www.mayoclinic.org/diseases-conditions/progeria/diagnosis-treatment/drc-20356043