"[…] our results, obtained from three MDPL patients, draw a picture of senescent mesenchymal cells with clear morphological abnormalities."
BUFFALO, NY- January 14, 2025 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 22 on November 26, 2024, entitled " When do the pathological signs become evident? Study of human mesenchymal stem cells in MDPL syndrome. "
Researchers from the University of Rome Tor Vergata , Fondazione Policlinico Tor Vergata , Roma Tre University , and Meyer Children's Hospital IRCCS have identified early cellular changes associated with Mandibular Hypoplasia, Deafness, Progeroid Features, and Lipodystrophy (MDPL) syndrome, a rare genetic aging disorder caused by a mutation in the POLD1 gene. MDPL leads to fat loss, distinct facial features, and metabolic disturbances. This study aimed to better understand how MDPL progresses at the cellular level.
MDPL syndrome is extremely rare, with only a few documented cases worldwide, making it difficult to study. To investigate the disease, researchers Spitalieri Paola, Guerrieri Lara, Murdocca Michela, Di Cesare Silvia, Maccaroni Serena, Pecorari Rosalba, Nardone Anna Maria, Candi Eleonora, Colasuonno Fiorella, Gori Giulia, Traficante Giovanna, Novelli Giuseppe, and Sangiuolo Federica, converted skin cells from three female MDPL patients and two healthy donors into human induced pluripotent stem cells (hiPSCs). These hiPSCs were then transformed into mesenchymal stem cells (MSCs), cells that can form tissues like bone and fat, which are primarily affected in MDPL syndrome.
The study revealed that MSCs from MDPL patients exhibited signs of premature aging much earlier than expected. The cells had irregular shapes, grew at a slower rate, and showed higher levels of cellular stress.
"These cells differentiate with lower efficiency, proliferate more slowly and have abnormal mitochondrial activity with increased production of ROS. Furthermore, the telomeres show evident shortening."
All the findings suggest that aging-related changes may occur long before patients display visible symptoms of the disease. This highlights the need for early diagnosis and intervention, which could delay or even prevent the most debilitating effects of MDPL syndrome.
In summary, this study offers new perspectives on the initial cellular impacts of MDPL, opening the door for the creation of novel treatments. The findings highlight the potential for personalized therapies and emphasize the critical role of lab-created hiPSCs in advancing research on rare genetic diseases and age-related conditions.
Read the full paper: DOI: https://doi.org/10.18632/aging.206159
