Age-Dependent Effects of Voluntary Wheel Running Exercise on Voiding Behavior and Potential Age-Related Molecular Mechanisms in Mice

Teresa T Liu; Laura E Pascal; Scott R Bauer; Hannah N Miles; Jules B Panksepp; Granville L Lloyd; Lingjun Li; Donald B DeFranco; William A Ricke

doi:10.1093/gerona/glae007

Age-Dependent Effects of Voluntary Wheel Running Exercise on Voiding Behavior and Potential Age-Related Molecular Mechanisms in Mice

J Gerontol A Biol Sci Med Sci. 2024 Jan 10:glae007. doi: 10.1093/gerona/glae007. Online ahead of print.

Authors

Teresa T Liu¹, Laura E Pascal^{2

3}, Scott R Bauer^{4

5}, Hannah N Miles^{1

6}, Jules B Panksepp⁷, Granville L Lloyd⁸, Lingjun Li^{6

9}, Donald B DeFranco², William A Ricke¹

Affiliations

¹ Department of Urology, George M. O'Brien Center of Research Excellence, University of Wisconsin - Madison, Madison, WI.
² Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA.
³ UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA.
⁴ Department of Medicine, Urology, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA.
⁵ San Francisco VA Medical Center, San Francisco, CA.
⁶ School of Pharmacy, University of Wisconsin - Madison, Madison, WI.
⁷ Waisman Center, University of Wisconsin - Madison, Madison, WI.
⁸ Department of Surgery/Urology, Rocky Mountain Regional VA Medical Center, University of Colorado Anschutz School of Medicine, Aurora, CO.
⁹ Department of Chemistry, University of Wisconsin - Madison, Madison, WI.

PMID: 38198648
DOI: 10.1093/gerona/glae007

Abstract

Background: Older men frequently develop lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH). Risk factors for LUTS/BPH include sedentary lifestyle, anxiety/depression, obesity, and frailty, which all increase with age. While physical exercise may reduce the progression and/or severity of LUTS/BPH, the age-related mechanisms responsible remain unknown.

Methods: Voiding symptoms, body mass, and frailty were assessed after 4-weeks of voluntary wheel running in 2-month (n=10) and 24-month (n=8) old C57Bl/6J male mice. In addition, various social and individual behaviors were examined in these cohorts. Finally, cellular and molecular markers of inflammation and mitochondrial protein expression were assessed in prostate tissue and systemically.

Results: Despite running less (aged vs young X̄=12.3 vs 30.6km/week;P=0.04), aged mice had reduced voiding symptoms (X̄=67.3 vs 23.7;P<0.0001) after one week of exercise, which was sustained through week 4 (X̄=67.3 vs 21.5;P<0.0001). Exercise did not affect voiding symptoms in young mice. Exercise also increased mobility and decreased anxiety in both young and aged mice (P<0.05). Exercise decreased expression of a key mitochondrial protein (PINK1;P<0.05) and inflammation within the prostate (CD68;P<0.05 and PAI-1;P<0.05) and in the serum (P<0.05). However, a frailty index (X̄=0.17 vs 0.15;P=0.46) and grip strength (X̄=1.10 vs 1.19;P=0.24) were unchanged after 4 weeks of exercise in aged mice.

Conclusion: Voluntary aerobic exercise improves voiding behavior, mobility, and decreases prostatic mitochondrial protein expression and inflammation in aged mice. This promising model could be used to evaluate molecular mechanisms of aerobic exercise as a novel lifestyle intervention for older men with LUTS/BPH.

Keywords: Lower urinary tract symptoms; benign prostatic hyperplasia; physical activity; pre-clinical mouse model; translational.

Abstract

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