Pregnancy-associated plasma protein-A deficiency improves survival of mice on a high fat diet

• Published in: Experimental gerontology Vol. 70; pp. 131 - 134
• Main Authors: Conover, Cheryl A., Bale, Laurie K., Marler, Ronald J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01-10-2015
• Subjects: Adipose Tissue - pathology; Aging - pathology; Animals; Body Composition - physiology; Diet, High-Fat - adverse effects; Disease Models, Animal; Gene knock-out; Heart Diseases - etiology; Heart Diseases - pathology; High fat diet; Intra-Abdominal Fat - pathology; Kidney Diseases - etiology; Kidney Diseases - pathology; Lifespan; Longevity - physiology; Male; Mice, Knockout; Mouse model; Organ Size - physiology; Pregnancy-associated plasma protein-A; Pregnancy-Associated Plasma Protein-A - deficiency; Pregnancy-Associated Plasma Protein-A - genetics; Pregnancy-Associated Plasma Protein-A - physiology; Survival Analysis; Testicular Diseases - etiology; Testicular Diseases - pathology; Weight Gain - physiology; Gene knock-out; KO; HFD; Pregnancy-associated plasma protein-A; PAPP-A; NSP; Mouse model; WT; Lifespan; High fat diet
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2015.08.007

Obesity is on the rise in westernized countries, and visceral obesity in particular is associated with enhanced risk of developing metabolic disease and accelerated aging. Various dietary restriction regimens have been shown to extend healthy lifespan in a variety of species. However, identification of alternative approaches that could be more acceptable to humans is actively being pursued. We have shown previously that mice deficient in pregnancy-associated plasma protein-A (PAPP-A) have an extended healthy lifespan on a regular chow diet. In this study, we determined the lifespan of PAPP-A knock-out (KO) and wild-type (WT) littermates fed a high fat diet (HFD) starting at 12months of age. PAPP-A KO and WT mice had equivalent weight gain as measured over 25weeks on HFD. However, PAPP-A KO mice on HFD had a significant increase in lifespan (P=0.018). Body composition and tissue pathology were assessed in a separate cohort of mice after 30weeks on HFD. Percent body fat was equivalent in the two groups. However, there was a decrease in visceral fat depot weights and an increase in serum adiponectin levels in PAPP-A KO compared to WT mice. Major pathological differences were seen in kidney, heart and testes, with PAPP-A KO mice having little, if any, evidence of inflammation, mineralization, or degeneration in these tissues compared to WT mice. Thus, PAPP-A is a novel drug target with the potential to promote healthy longevity without a need for dietary restriction.