Klotho protein as a marker and target for the development of strategies to identify agents that slow aging and the progression of age-related diseases

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Abstract

There is a steady increase in life expectancy and in the number of elderly individuals worldwide. Aging is associated with the rise of age-related diseases and multimorbidity and therefore has become a major medical, social, and economic challenge for the state. This imposes new tasks on the healthcare system, social support services, and the state as a whole, aimed at ensuring healthy and active longevity and at developing new health-preserving technologies and strategies. Multiple pathophysiological processes underlie aging and the development of age-related diseases: oxidative stress, chronic low-grade inflammation, mitochondrial dysfunction, reduced autophagy, accumulation of damage to proteins and subcellular and cellular structures, and a decline in the functional capacity of organs and systems. All of this stimulates the development of new strategies for maintaining healthy and active longevity through agents exerting polyvalent effects on the main pathophysiological mechanisms of age-associated changes. The discovery of the gene responsible for the synthesis of the protein that slows aging, named after the goddess who spins the thread of life-Klotho-sparked great interest among biologists and specialists in theoretical and clinical medicine. The geroprotective action is based on the inhibition of four pathways: 1) insulin-like growth factor-1 of the Klotho protein (IGF-1), 2) transforming growth factor-β1 (TGF-β1), 3) Wnt and 4) nuclear transcription factor (NF-κB). Their activation is associated with inflammation, oxidative and nitrosative stress, reduced autophagy, immune dysfunction, mitochondrial dysfunction, neoplasia, cellular senescence, apoptosis and premature cell death, a decline in the morphofunctional reserves of various organs and systems, and reduced adaptive mechanisms and resistance of the organism to adverse external and internal factors. The review provides a concise description of the anti-aging protein Klotho, considers its biological activity and the dynamics of its serum levels depending on age and on the functional state of the organism under normal and pathological conditions. It is shown that its serum level can be increased by certain medicinal agents and by adherence to healthy lifestyle factors, including work-rest balance, regular physical activity and sports, diet, healthy sleep, and others.

Conclusions: The Klotho protein plays an important role in the regulation of aging processes and the development of age-related diseases and therefore may serve as a target for the search and development of medicinal agents that increase its production for the prevention of early aging and the treatment of age-associated pathologies. The multifunctional Klotho protein may represent a new and economically justified biomarker of aging and an integral tool for qualitative and quantitative assessment of lifestyle, biological age, and overall health status.

About the authors

Ivan N. Tyurenkov

Volgograd State Medical University

Author for correspondence.
Email: fibfuv@mail.ru
ORCID iD: 0000-0001-7574-3923

holder of an Advanced Doctorate (Doctor of Science) in Medical Sciences, Professor

Russian Federation, Volgograd

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