ArticleCardiovascular diabetology2017
DPP-4 inhibition with linagliptin ameliorates the progression of premature aging in klotho-/- mice.
Article in Cardiovascular diabetology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
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Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress.Frontiers in pharmacology · 2024Pooled it
- Dipeptidyl peptidase-4 inhibitors alleviate cognitive dysfunction in type 2 diabetes mellitus.Lipids in health and disease · 2023Pooled it
- HIF-1α attenuates ferroptosis-associated dermal fibroblast senescence via modulation of NF-κB-DPP4 signaling.Journal of translational medicine · 2026Article
- Eyedrop Administration of DPP-4 Inhibitors: A New Strategy for Treating Early Stages of Diabetic Retinal Disease.International journal of molecular sciences · 2026Review
- Restoring Brain Pathways Involved in Diabetes-Associated Neurocognitive Disorders: The Potential of Dipeptidyl Peptidase 4 Inhibitors as a Therapeutic Strategy.Current neuropharmacology · 2025Article
- Effects of Hypoglycemic Agents on The Musculoskeletal System: A Comprehensive Review.Drug design, development and therapy · 2025Review
- Systemic DPP4/CD26 is associated with natural HIV-1 control: Implications for COVID-19 susceptibility.Clinical immunology (Orlando, Fla.) · 2021Article
- [Alopecia areata universalis under treatment with sitagliptin : Possible immunological effect of dipeptidyl peptidase-4 inhibitors?]Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete · 2021Article
- Effects of anagliptin on the stress induced accelerated senescence of human umbilical vein endothelial cells.Annals of translational medicine · 2021Article
- Roles and Mechanisms of Dipeptidyl Peptidase 4 Inhibitors in Vascular Aging.Frontiers in endocrinology · 2021Review
- Pleiotropic Benefits of DPP-4 Inhibitors Beyond Glycemic Control.Clinical medicine insights. Endocrinology and diabetes · 2021Review
- Accelerated Kidney Aging in Diabetes Mellitus.Oxidative medicine and cellular longevity · 2020Review
- The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Ameliorates High-fat Induced Cognitive Decline in Tauopathy Model Mice.International journal of molecular sciences · 2019Article
- Diabetes pharmacotherapy and effects on the musculoskeletal system.Diabetes/metabolism research and reviews · 2019Review
- Dipeptidyl Peptidase-4 Inhibitors for the Potential Treatment of Brain Disorders; A Mini-Review With Special Focus on Linagliptin and Stroke.Frontiers in neurology · 2019Review
- The effect of DPP-4 inhibition to improve functional outcome after stroke is mediated by the SDF-1α/CXCR4 pathway.Cardiovascular diabetology · 2018Article
- The role of dipeptidylpeptidase-4 inhibitors in management of cardiovascular disease in diabetes; focus on linagliptin.Cardiovascular diabetology · 2018Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 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.
methodsKlotho-/- 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.
resultsBody 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.
conclusionsOut 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.
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