Research Highlights

Understanding premature aging

Published online 10 August 2009

Mohammed Yahia

Wrinkled skin and loss of bone are usually the first signs of ageing. However, some diseases can lead to the premature appearance of these changes. This results in a progeroid phenotype in relatively young people. One such disease is autosomal recessive cutis laxa type II (ARCL2), which a group of researchers, led by Dr. Bruno Reversade, investigated further to uncover its genetic origin.

Patients suffering ARCL2 often show osteopenia, wrinkled skin and mental retardation. Using homozygosity mapping followed by targeted genomic pull-down and high-throughput sequencing on different samples, the researchers were able to identify the gene causing the condition as PYCR1.

The enzyme produced by this gene control the production of the amino acid proline, which is a major constituent of skin and bone tissues. The enzyme is mainly found in mitochondria. Mutations in the gene led to formation of abnormally structured mitochondria and made them more susceptible to oxidative stress, leading to an increase in cell death. This suggests that PYCR1 plays an important role in the cell ability to cope with oxidative compounds, such as those generated during normal metabolism.

The study stresses the importance of mitochondria in slowing down the process of ageing. The researchers are hopeful that their findings may help in the development of new remedies for common age-related disorders.


  1. Reversade, B. et al. Mutations in PYCR1 cause cutis laxa with progeroid features. Nature Genetics 41, 1016-1021 (2009) | Article | PubMed |