Relationship of Low-Circulating “Anti-Aging” Klotho Hormone with Disability in Activities of Daily Living among Older Community-Dwelling Adults

Abstract

The aging suppressor gene klotho encodes a single-pass transmembrane protein klotho that in mice is known to extend life span when overexpressed and to resemble accelerated aging, with skeletal muscle atrophy and decreased bone mineral density, when expression is disrupted. We sought to examine the relationship between plasma klotho and disability in activities of daily living (ADL) in older community-dwelling adults. In a crosssectional study, plasma klotho was measured in a population-based sample of 802 adults, ‡ 65 years, who participated in the ''Invecchiare in Chianti'' (Aging in the Chianti Area) (InCHIANTI) study in Tuscany, Italy. The overall proportion of adults with ADL disability was 11.9%. Mean (standard deviation) klotho concentrations were 689 (238) pg/mL. From the lowest to the highest tertile of plasma klotho, 16.1%, 9.7%, and 5.6% of participants, respectively, had ADL disability ( p = 0.0004). Plasma klotho, per 1 standard deviation increase, was associated with ADL disability (odds ratio = 0.57, 95% confidence interval 0.35-0.93, p = 0.02) in a multivariate logistic regression model adjusting for age, education, cognition, physical activity, physical performance, total cholesterol, alcohol and tobacco use, and chronic diseases. Low plasma klotho concentrations were independently associated with ADL disability among older community-dwelling men and women.

Association of Serum Klotho with Loss of Bone Mineral Density and Fracture Risk in Older Adults

“…The findings of this report show that serum klotho levels are not associated with baseline BMD, bone loss, or fracture risk in older individuals. These novel findings suggest that, although the klotho gene is a susceptibility gene for reduced BMD and lower serum klotho (<575 pg/mL) is related to greater declines in grip strength and higher disability, klotho blood levels were unrelated to bone loss or fracture risk in older adults. A possible explanation for the lack of association is the pleotropic function of the klotho gene .…”

Klotho and smoking – An interplay influencing the skeletal muscle function deficits that occur in COPD

“…The groups were well matched except that 'healthy smokers' were significantly younger than both never smokers and COPD patients; this is relevant since in population studies circulating Klotho falls with increasing age (8). The COPD patients had evidence of quadriceps weakness.…”

“…Serial data from a single cohort of older adults in a general population, has linked low circulating Klotho levels with reduced grip strength (1), disability (8) and increased mortality (9).…”

Klotho, Fgf21 and Fgf23: Novel Pathways to Musculoskeletal Health?

“…Extracellular phosphate is necessary to allow mineralization of bone matrix, while intracellular phosphate plays an important role in energy stores and production (e.g. in the form of phosphocreatine and ATP) (77), which are needed for muscles to function. Consequently, klotho and FGF23 may play an important role not only in bone mineralization but also in the maintenance of muscle mass and function given their interplay with vitamin D and the critical role of phosphate in energy (ATP) and protein production.…”

“…However, despite this strong theoretical basis, there is a gap in the current scientific knowledge on the effect of klotho, FGF21 and FGF23 on muscle mass and function in humans. Indeed, there are only two studies in humans published to date on this topic, and they show that one standard deviation increase in plasma klotho was significantly associated with muscle strength (β=1.20, standard error=0.35, p=0.0009)(76) and with reduced risk of developing Activities of Daily Living disability (odds ratio=0.57, 95% confidence interval=0.35–0.93)(77) in Italian older persons. In conclusion, this mini-review provides a theoretical basis for the potential role of these emerging biomarkers on musculoskeletal health, with a particular focus on muscle mass and function.…”