Baseline Plasma GDF15 and Recovery of Physical Function Following Total Knee Replacement in The Study of Physical Resilience and Aging

Abstract

Growth-differentiation factor 15 (GDF15), a cytokine with the ability to regulate metabolic and inflammatory activity, is negatively associated with physical and cognitive function, and increases in circulation with age. Mechanistically, the expression of GDF15 is stimulated by mitochondrial stress across multiple tissues. We hypothesized elevations in basal circulating GDF15 were negatively associated with physical function following surgery in older adults. This was assessed in 112 Study of Physical Resilience and Aging (SPRING) participants (age 69.6 ± 6.9 years, 66% women) undergoing total knee replacement (RESTORE). The associations between pre-operative plasma GDF15 levels and longitudinal post-operative physical resilience measures including the Short Physical Performance Battery (SPPB) and Pittsburgh Fatigability Scale (PFS) were evaluated. At baseline, higher circulating GDF15 levels were associated with older age, higher BMI, diabetes, and physical frailty (P<0.05). Circulating GDF15 levels were not associated with SPPB or PFS scores prior to knee replacement (P>0.05). Higher baseline circulating GDF15 levels were negatively associated with the recovery of SPPB scores six months following knee replacement (P<0.05). However, there was no significant association between baseline circulating GDF15 levels and the recovery of PFS scores within the same timeframe (P>0.05). There were no significant associations between baseline circulating GDF15 and recovery of SPPB or PFS scores at 1-month or 12-months follow up (P>0.05). These findings suggest that pre-operative circulating GDF15 levels may provide some insight into the capacity to recover physical function following total knee replacement surgery. Further investigation is necessary to elucidate relationships between GDF15 and the biology of physical resilience.