Klotho: A Major Shareholder in Vascular Aging Enterprises

Abstract

Accelerated vascular aging is a condition that occurs as a complication of several highly prevalent inflammatory conditions such as chronic kidney disease, cancer, HIV infection and diabetes. Age-associated vascular alterations underlie a continuum of expression toward clinically overt cardiovascular disease. This has contributed to the striking epidemiologic transition whereby such noncommunicable diseases have taken center stage as modern-day global epidemics and public health problems. The identification of α-Klotho, a remarkable protein that confers powerful anti-aging properties has stimulated significant interest. In fact, emerging data have provided fundamental rationale for Klotho-based therapeutic intervention for vascular diseases and multiple other potential indications. However, the application of such discoveries in Klotho research remains fragmented due to significant gaps in our molecular understanding of Klotho biology, as well as hurdles in clinical research and experimental barriers that must first be overcome. These advances will be critical to establish the scientific platform from which future Klotho-based interventional trials and therapeutic enterprises can be successfully launched.

Soluble Alpha-Klotho Alleviates Cardiac Fibrosis without Altering Cardiomyocytes Renewal

“…MerCreMer-GR mice were generated by crossbreeding transgenic MerCreMer mice with R26-G/R: B6-Gt(ROSA)26Sor tm1Ytchn /J mice (Stock No. 021847, kindly provided by Dr. Shu-Wha Lin, National Taiwan University) [39]. Colony maintenance and all experiments were conducted in accordance with the Guide for the Use and Care of Laboratory Animals and approved by the IACUC Committee (IACUC number: 2014031903) of Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.…”

Klotho and the Treatment of Human Malignancies

“…In contrast, transgenic mice overexpressing alpha-Klotho had an extended life span of up to 30% compared to wild type mice [1,2]. These discoveries sparked immense interest into the role of alpha-Klotho in ageing, and many studies have since linked alpha-Klotho deficiency or mutations, to a number of age-related disease processes, including cardiovascular, renal, musculoskeletal, and neurodegenerative conditions [3,4]. In addition, emerging research has also highlighted the potential role of alpha-Klotho in the pathogenesis of human malignancies [5][6][7].…”

Klotho Pathways, Myelination Disorders, Neurodegenerative Diseases, and Epigenetic Drugs

“…3,18,27,102,183,184 A soluble form of Klotho (sKlotho), primarily secreted from the kidney, circulates in blood, urine, and cerebrospinal fluid, exerting different biological effects in multiple tissues as a humoral factor. 5,6,8,52,[185][186][187][188][189] In the eye, Klotho protects against OS 53,55,58,153,190,191 and is essential to the proper maintenance and function of the ocular system, 12,26,[192][193][194][195] being expressed throughout the retina, with the highest levels in retinal ganglion cells. 196 The retinal pigment epithelium (RPE) is a highly specialized CNS tissue whose function is critical in preserving retinal homeostasis 53,78 and an age-dependent decline of Klotho expression is said to contribute to RPE degeneration and retinal pathology.…”