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Review
. 2023 Dec 8;21(1):287.
doi: 10.1186/s12915-023-01779-9.

Geroprotector drugs and exercise: friends or foes on healthy longevity?

Christian J Elliehausen  1   2 , Rozalyn M Anderson  1   2 , Gary M Diffee  3 , Timothy W Rhoads  4   5 , Dudley W Lamming  6 , Troy A Hornberger  7 , Adam R Konopka  8   9
Affiliations
Review

Geroprotector drugs and exercise: friends or foes on healthy longevity?

Christian J Elliehausen et al. BMC Biol. .

Abstract

Physical activity and several pharmacological approaches individually combat age-associated conditions and extend healthy longevity in model systems. It is tantalizing to extrapolate that combining geroprotector drugs with exercise could extend healthy longevity beyond any individual treatment. However, the current dogma suggests that taking leading geroprotector drugs on the same day as exercise may limit several health benefits. Here, we review leading candidate geroprotector drugs and their interactions with exercise and highlight salient gaps in knowledge that need to be addressed to identify if geroprotector drugs can have a harmonious relationship with exercise.

Keywords: Acarbose; Aging; Geroscience; Healthspan; Metformin; Physical activity; Rapamycin; SGLT2 inhibitors; Skeletal muscle.

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Conflict of interest statement

D.W.L has received funding from, and is a scientific advisory board member of, Aeovian Pharmaceuticals, which seeks to develop novel, selective mTOR inhibitors for the treatment of various diseases.

Figures

Fig. 1
Fig. 1
Capitalizing on the combination of regular exercise and geroprotectors. Current dogma suggests combining geroprotectors with concurrent exercise blunts hallmarks of exercise that are associated with healthy longevity. Frequent (daily) dosing of leading geroprotectors blunts clinically relevant improvements to cardiorespiratory fitness, muscle size/strength/power, and insulin sensitivity. Along the aging continuum, identifying an appropriate age to begin intervening with combined approaches represents an opportunity to suppress the age-related decline in systemic health. Finally, manipulating dose or frequency of dosing may provide the opportunity to capitalize on the benefits of both regular exercise and geroprotectors to enhance healthy longevity to new heights. Created with BioRender.com
Fig. 2
Fig. 2
Current known and unknown interactions between leading geroprotectors and chronic exercise adaptations. Compared to regular exercise, frequent dosing of leading geroprotectors with concurrent exercise blunts many hallmark adaptions to exercise in populations without overt disease. Green up arrow, greater improvement with exercise training; red down arrow, blunted improvements with exercise; horizontal grey arrow, no different than exercise alone; question mark, indicates unknown interaction. Created with BioRender.com
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