Table 3.
Effects of exercise training on Klotho expression.
| Reference | Study design | Population | Sample and technique | Key findings |
|---|---|---|---|---|
| Amaro-Gahete et al. (193) | −12 weeks -control: no exercise -PA recommendations from WHO: 3 days/wk of both aerobic (150 min/wk at 60–65% HRR) and resistance exercise (~60 min/wk of 40–50% 1RM) -HIIT: 2 days/wk with two different protocols: 40–65 min/wk at >95% VO2max using a treadmill (session A) and >120% VO2max using a circuit workout (session B) -HIIT-EMS: same as HIIT plus whole-body electromyostimulation |
Sedentary middle-aged adults (n = 68, 32 men, age 53.4 ± 5.0) randomly assigned to control (n = 15), PAR (n = 17), HIIT (n = 17), and HIIT-EMS (n = 19) | -Plasma -ELISA (Demeditec, Kiel, Germany) |
-↑ in sKlotho following all exercise interventions compared to baseline and control. -No significant difference between the training groups. |
| Dalise et al. (192) | -4 weeks, 5 days per week -Treadmill running at 80% of their maximal baseline activity or NMES at three different doses: -Low: 15 min running or 1 set of 10 stimulations -Medium duration: 30 min running or 2 sets of 10 stimulations -high duration: 60 min running or 3 sets of 10 stimulations -Control: no treatment |
Male Sprague-Dawley Rats, 12 weeks of age randomized into 7 treatment groups: low (n = 5), medium (n = 5), and high (n = 5) running, low (n = 5), medium (n = 5), and high (n = 5) NMES, and control (n = 10). | -Hippocampal tissue -ELISA (CSB-E14958r, CUSABIO) -qPCR (#Rn00580123_m1, Applied Biosystems |
-↑ in sKlotho levels for all running conditions compared to control, with the highest level being produced by the medium condition. -NMES did not significantly affect sKlotho levels. -↑ in Klotho mRNA expression in the hippocampus in all exercise groups compared to control except the low running group. |
| Fakhrpour et al. (195) | -16 weeks, 3 days per week -Combined intradialytic aerobic and resistance training -Aerobic exercise: progressive cycling beginning at 10 min duration at a comfortable pace with 5–10 min increases per session with a goal of 45 min per session at 12–14 RPE. -Resistance training: lower extremity exercises at an intensity of 9–15 RPE starting at ~20% 1RM for 2 sets of 12 reps and increased to 3 sets as tolerable. Resistance increased to 40, 55, and 65% 1RM as tolerated. |
Hemodialysis patients (n = 45, 38 men, age 61.0 ± 9.0) randomly assigned to control (n = 21) and intradialytic exercise training (n = 24). | -Serum -ELISA (IBL Ltd., Tokyo, Japan) |
-↑ in sKlotho compared to baseline and compared to control. -↓ in sKlotho in the control patients. |
| Gaitan et al. (187) | -26 weeks, 3 days per week -Usual Physical Activity (UPA): maintained their usual level of PA -Enhanced Physical Activity (EPA): Participated in supervised, progressive, moderate-to-vigorous intensity aerobic exercise. |
Sedentary middle-aged adults with family history of Alzheimer's disease (n = 23) were randomized to either UPA (n = 12, 6 men, age 63.9 ± 5.2) or EPA (n = 11, 6 men, age 65.9 ± 4.0 years). | -Serum -ELISA (IBL Ltd., Takasaki, Japan) |
-No changes in sKlotho in either group. -Changes in sKlotho were positively correlated with changes in VO2peak. |
| Ji et al. (191) | -48 weeks, 5 days per week, 60 min per day -Intermittent aerobic exercise (IAE): 10 m/min (40–50% VO2max) for 10 min, 25 m/min (80–90% VO2max) for 7 min and 15 m/min (50–60% VO2max for 3 min, repeat 2x. -Continuous aerobic exercise (CAE): 16 m/min (50–60% VO2max). -Control: no exercise |
Male Sprague-Dawley Rats, 3 months old randomized to control (n = 30), IAE (n = 31), and CAE (n = 32) | - Kidneys and brain. -RT-qPCR (upstream primer: 5'-ATC CGG CCT CAG ATA ACC TT-3'; downstream primer: 5'-CCA CCA CTG GAG TGA TGT TG-3') -Western blot (ab203576; 1:2,000, Abcam, Cambridge, UK) |
-↑ in Klotho mRNA and protein (116 kDa) expression in brain and kidneys in CAE and IAE compared to control. -No difference between exercise groups. |
| Matsubara et al. (129) | -12 weeks, 3–4 days per week (2–3 supervised sessions and home-based training) -Cycling and walking for 30 min/day at 60% max HR -Increased to 40–60 min/day at 70–80% max HR as tolerated -Control: no exercise |
Healthy and postmenopausal women (n = 19, aged 62 ± 2.5) 50–76 years old) divided into control (n = 8) and exercise group (n = 11). | -Plasma -ELISA (IBL Ltd., Tokyo, Japan) |
-↑ in sKlotho in the exercise group compared to baseline. -No change in sKlotho in the control group. |
| Middelbeek et al. (194) | −2 weeks, 6 total training sessions -Sprint interval training (SIT): 6 × 30 s maximal cycle ergometer sprints with 4 min of recovery -Moderate intensity continuous training (MIT): Cycling at 60% VO2peak for 40 min (sessions 1–3) and 60 min (sessions 3–6). |
Healthy middle-aged men (n = 22, age 48 ± 5 years) randomized into SIT (n = 12) and MIT (n = 10) | -Serum -ELISA (NeoBioLab, #HK0034) |
-↑ in sKlotho following MIT program -No change in sKlotho following SIT program |
| Neves et al. (196) | -6 months, 3 days per week, ~40 min per day, ~1 hour before dialysis -Dynamic resistance training (DRT): Full body resistance training using elastic bands and free weights. -Isometric resistance training (IRT): same exercise as DRT but performed isometrically. |
Maintenance hemodialysis patients were randomized into control (n = 60, 30 men, age 55 ± 12 years), DRT (n = 66, 33 men, age = 58 ± 15 years), and IRT (n = 67, 31 men, age = 56 ± 19) | -Plasma -ELISA (IBL Ltd., Japan) |
-↑ in sKlotho following DRT compared to baseline, IRT and control. -↑ in sKlotho following IRT compared to control. |
| Rahimi et al. (182) | -12 weeks, 3 days per week -Water Aerobic program: Starting at 30 min (60% of max HR) then progressing to 40–60 min (70–80% max HR). |
Healthy non-athlete women (n = 10, age 32 ± 7 years) and healthy female athletes (n = 10, age 31 ± 9 years). | -Plasma -ELISA (IBL, D-22335, Hamburg, Germany) |
-↑ in sKlotho 24 hours after training intervention in athlete group compared to baseline and non-athletes. -No change in sKlotho following training intervention in non-athlete group. |
| Saghiv et al. (189) | -12 months, 4–5 times per week -supervised aerobic programs at 60–75% work capacity. |
CAD patients that participated in the exercise program (n = 60, age 53.0 ± 2.0 years), untrained CAD patients (n = 60, age 52.6 ± 2.0 years), and untrained healthy men (n = 40, age 53.6 ± 1.5 years) | -Serum -ELISA (IBL Ltd., Japan) |
-↑ sKlotho was observed the trained CAD patients compared to both untrained CAD patients and untrained healthy men. |
| Saghiv et al. (190) | -12 weeks, 4–5 days per week, 45 min per day. -Individualized cardiac rehabilitation programs at 75–80% of max HR. -Control: no exercise intervention |
CAD patients (n = 41, 30 men, age 59.6 ± 2.2 years) who performed cardiac rehabilitation and age-matched control CAD patients (n = 17, 12 men, age 61 ± 2.4 years). | -Serum -ELISA (IBL Ltd., Japan) |
-↑ in sKlotho levels following the exercise program compared to baseline. -No change in sKlotho in the control group. |
| Saghiv et al. (188) | -6 months, 4 days per week, 45 min per day. -Treadmill running -Low training intensity (LTI): 40–50% VO2max High training intensity (HTI): 65–70% VO2max |
Young, healthy, untrained men (n = 60, age 27.0 ± 1.1 years) were randomized into LTI (n = 30) and HTI (n = 30). | -Serum -ELISA (IBL Ltd., Japan) |
-↑ in sKlotho in the HTI group at 2 and 4 months of training compared to baseline. -sKlotho was higher in HTI compared to LTI at 2, 4, and 6 months of training. -no change in sKlotho was observed for the LTI group. |
PA, physical activity; WHO, World Health Organization; HRR, heart rate reserve; ELISA, enzyme-linked immunosorbent assay; IBL, Immuno-Biological Laboratories; sKlotho, soluble Klotho; NMES, neuromuscular electrical stimulation; RPE, ratings of perceived exertion; VO2peak, peak oxygen uptake; VO2max, maximum oxygen uptake; CAD, coronary artery disease.