Relationship between dietary factors and S-Klotho plasma levels in young sedentary healthy adults

Highlights

• S-Klotho has emerged as important anti-ageing biomarker related to the promotion of health span.

• Ethanol intake was directly associated with S-Klotho plasma levels in women.

• A pro-inflammatory diet was inversely associated with S-Klotho plasma levels in young adults, being partially mediated by LMI and uric acid level.

Abstract

Objective

To study the associations of dietary factors with S-Klotho plasma levels in young adults. We also aimed to study whether body composition and cardiometabolic risk factors affected the association between dietary factors and S-Klotho plasma levels.

Methods

A total of 139 young adults took part in this study. Dietary factors were measured using a food frequency questionnaire and three non-consecutive 24 h recalls. S-Klotho plasma levels were measured by immunosorbent assay. Body composition was measured by DXA.

Results

We observed a direct association of ethanol intake and S-Klotho plasma levels in women. An inverse association was also observed between the dietary inflammatory index (DII) with S-Klotho plasma levels in all sample. No mediation effects of body composition or cardiometabolic risk factors were observed in the relationship between alcohol and S-Klotho plasma levels. Lean mass index (LMI) and uric acid levels mediated the relationship between DII and S-Klotho plasma levels.

Conclusion

A pro-inflammatory dietary pattern was inversely associated with S-Klotho plasma levels in young adults, which was partially mediated by LMI and uric acid levels.

Introduction

Life expectancy has importantly increased in developed countries during the last century (Kontis et al., 2017) with the consequent increment of chronic disease incidence (Chang et al., 2019). Recently, new aging biomarkers have grown in popularity due to their robust relationship with morbi-mortality risk and life expectancy, such as the Klotho protein (Kuro-O, 2010; Kurosu et al., 2005; Cheikhi et al., 2019). Klotho is a transmembrane protein highly expressed in the kidney, which has been identified as an aging suppressor agent (Kuro-o et al., 1997). The transmembrane Klotho could undergo proteolytic cleavage or alternatively splicing generating a secreted form (i.e. S-Klotho), which is released in the peripheral circulation to reach different tissues and exerting diverse metabolic actions (Cheikhi et al., 2019; Kuro-o et al., 1997; Kuro-o, 2019).

S-Klotho has different health-related physiological functions including the modulation of endothelial nitric oxide synthesis (Nagai et al., 2000; Saito et al., 1998), the maintenance of endothelial integrity (Dalton et al., 2017), and the modulation of the action of hormones and molecules such as insulin, insulin-like growth factor I, transforming growth factor-β, Wnt signalling, and gamma interferon acting as a paracrine and/or endocrine mediator (Kuro-o, 2019; Dalton et al., 2017). In fact, growing evidence suggests that α-Klotho suppresses the insulin and Wnt signalling pathways, inhibits oxidative stress, and regulates phosphatase and calcium absorption (Xu and Sun, 2015). Indeed, high levels of S-Klotho have been associated with a healthier body composition (Amaro-Gahete et al., 2019a), greater physical fitness (Amaro-Gahete et al., 2019b), and metabolic flexibility during exercise (Amaro-Gahete et al., 2019c), and with a lower risk of cardiovascular disease (Semba et al., 2011a) and all-cause mortality (Semba et al., 2011b).

Age-related diseases may be influenced by different dietary factors during the life course and adulthood (Shlisky et al., 2017). In this sense, previous studies have reported a direct association between nuts consumption and S-Klotho plasma levels (Jurado-Fasoli et al., 2019a), and an inverse association between alcoholic drinks consumption and S-Klotho plasma levels in middle-aged adults (Jurado-Fasoli et al., 2019b). Whether this is the case in younger individuals free of disease is currently unknown. The study of the aging process should be focused not only in adults, but also in younger populations since they represent an attractive target for therapies to increase lifespan and to prevent age-related diseases (Belsky et al., 2015). Therefore, it is of clinical interest to study which dietary factors could modulate S-Klotho plasma levels already in young adults.

This study aimed to investigate the association of dietary factors (i.e. energy and macronutrient intake, food groups consumption and dietary patterns) with S-Klotho plasma levels in sedentary young but otherwise healthy adults. Given that (i) S-Klotho plasma levels have been strongly associated with body composition and cardiometabolic risk parameters (Amaro-Gahete et al., 2019a; Semba et al., 2011a), and (ii) that diet can influence both body composition and cardiometabolic risk factors (Mozaffarian, 2017), we also aimed to study the mediation role of body composition and cardiometabolic risk factors in the association between dietary factors and S-Klotho plasma levels.