Neuropeptide Y Enhances Progerin Clearance and Ameliorates the Senescent Phenotype of Human Hutchinson-Gilford Progeria Syndrome Cells.

Aveleira, Célia A; Ferreira-Marques, Marisa; Cortes, Luísa; Valero, Jorge; Pereira, Dina; Almeida, Luís Pereira de; Cavadas, Cláudia; Pereira de Almeida, Luís

Hutchinson-Gilford progeria syndrome (HGPS, or classical progeria) is a rare genetic disorder, characterized by premature aging, and caused by a de novo point mutation (C608G) within the lamin A/C gene (LMNA), producing an abnormal lamin A protein, termed progerin. Accumulation of progerin causes nuclear abnormalities and cell cycle arrest ultimately leading to cellular senescence. Autophagy impairment is a hallmark of cellular aging, and the rescue of this proteostasis mechanism delays aging progression in HGPS cells. We have previously shown that the endogenous Neuropeptide Y (NPY) increases autophagy in hypothalamus, a brain area already identified as a central regulator of whole-body aging. We also showed that NPY mediates caloric restriction-induced autophagy. These results are in accordance with other studies suggesting that NPY may act as a caloric restriction mimetic and plays a role as a lifespan and aging regulator. The aim of the present study was, therefore, to investigate if NPY could delay HGPS premature aging phenotype. Herein, we report that NPY increases autophagic flux and progerin clearance in primary cultures of human dermal fibroblasts from HGPS patients. NPY also rescues nuclear morphology and decreases the number of dysmorphic nuclei, a hallmark of HGPS cells. In addition, NPY decreases other hallmarks of aging as DNA damage and cellular senescence. Altogether, these results show that NPY rescues several hallmarks of cellular aging in HGPS cells, suggesting that NPY can be considered a promising strategy to delay or block the premature aging of HGPS.

PROGERIA; NEUROPEPTIDE Y; PREMATURE aging (Medicine); CELLULAR aging; HUMAN phenotype; PROTEIN metabolism; AUTOPHAGY; COMPARATIVE studies; FIBROBLASTS; RESEARCH methodology; MEDICAL cooperation; INBORN errors of metabolism; NEUROPEPTIDES; RESEARCH; SKIN; EVALUATION research

Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2020, Vol 75, Issue 6, p1073

1079-5006

Academic Journal

10.1093/gerona/glz280