NDLI: DPP-4 inhibition with linagliptin ameliorates the progression of premature aging in klotho−/− mice

Content Provider	Springer Nature : BioMed Central
Author	Hasegawa, Yu Hayashi, Kenyu Takemoto, Yushin Cheng, Cao Takane, Koki Lin, Bowen Komohara, Yoshihiro Kim-Mitsuyama, Shokei
Abstract	Background The potential of anti-aging effect of DPP-4 inhibitors is unknown. This study was performed to determine whether linagliptin, a DPP-4 inhibitor, could protect against premature aging in klotho−/− mice. Methods Klotho−/− mice exhibit multiple phenotypes resembling human premature aging, including extremely shortened life span, cognitive impairment, hippocampal neurodegeneration, hair loss, muscle atrophy, hypoglycemia, etc. To investigate the effect of linagliptin on these aging-related phenotypes, male klotho−/− mice were divided into two groups: (1) control group fed the standard diet, and (2) linagliptin group fed the standard diet containing linagliptin. Treatment with linagliptin was performed for 4 weeks. The effect of linagliptin on the above mentioned aging-related phenotypes was examined. Results Body weight of klotho−/− mice was greater in linagliptin group than in control group (11.1 ± 0.3 vs 9.9 ± 0.3 g; P < 0.01), which was associated with greater gastrocnemius muscle weight (P < 0.01) and greater kidney weight (P < 0.05) in linagliptin group. Thus, linagliptin significantly prevented body weight loss in klotho−/− mice. Survival rate of klotho−/− mice was greater in linagliptin group (93%) compared to control group (67%), although the difference did not reach statistical significance (P = 0.08). None of linagliptin-treated klotho−/− mice had alopecia during the treatment (P < 0.05 vs control klotho−/− mice). Latency of klotho−/− mice in passive avoidance test was larger in linagliptin group than in control group (P < 0.05), indicating the amelioration of cognitive impairment by linagliptin. Cerebral blood flow of klotho−/− mice was larger in linagliptin group than in control group (P < 0.01), being associated with greater cerebral phospho-eNOS levels (P < 0.05) in linagliptin group. Neuronal cell number in hippocampal CA1 region was greater in linagliptin group than in control group (P < 0.05). Linagliptin group had greater cerebral phospho-Akt (P < 0.05) and phospho-CREB (P < 0.05) than control group. Thus, linagliptin ameliorated brain aging in klotho−/− mice. The degree of hypoglycemia in klotho−/− mice was less in linagliptin group than in control group, as estimated by the findings of OGTT. Conclusions Out work provided the evidence that DPP-4 inhibition with linagliptin slowed the progression of premature aging in klotho−/− mice, and provided a novel insight into the potential role of DPP-4 in the mechanism of premature aging.
Related Links	https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-017-0639-y.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	14752840
DOI	10.1186/s12933-017-0639-y
Journal	Cardiovascular Diabetology
Issue Number	1
Volume Number	16
Language	English
Publisher	BioMed Central
Publisher Date	2017-12-01
Access Restriction	Open
Subject Keyword	Diabetes Angiology Cardiology Premature aging DPP-4 Klotho−/− mice Cognition Brain aging Pleiotropic effect
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Internal Medicine Endocrinology, Diabetes and Metabolism
Journal Impact Factor	8.5/2023
5-Year Journal Impact Factor	8.9/2023

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DPP-4 inhibition with linagliptin ameliorates the progression of premature aging in klotho−/− mice

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