Fountain William A, Milcik Nicholas, Schmedding Nicholas, Bandeen-Roche Karen, Alzahrani Mallak K, Buta Brian, Dobrosielski Meredith, Langdon Jackie, Sieber Frederick, Oni Julius K, Laskow Thomas, Xue Qian-Li, Varadhan Ravi, Walston Jeremy
Department of Medicine, School of Medicine, Division of Geriatric Medicine and Gerontology, Johns Hopkins University, Baltimore, Maryland, USA.
Center on Aging and Health, Medical Institutions, Johns Hopkins University, Baltimore, Maryland, USA.
J Gerontol A Biol Sci Med Sci. 2025 May 28. doi: 10.1093/gerona/glaf115.
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.
生长分化因子15（GDF15）是一种具有调节代谢和炎症活性能力的细胞因子，与身体和认知功能呈负相关，并随年龄增长而在循环中升高。从机制上讲，GDF15的表达受到多个组织中线粒体应激的刺激。我们假设，基础循环GDF15升高与老年人术后身体功能呈负相关。在112名接受全膝关节置换术（RESTORE）的身体恢复力与衰老研究（SPRING）参与者（年龄69.6±6.9岁，66%为女性）中对此进行了评估。评估了术前血浆GDF15水平与术后纵向身体恢复力指标之间的关联，这些指标包括简短身体表现量表（SPPB）和匹兹堡疲劳量表（PFS）。在基线时，较高的循环GDF15水平与年龄较大、体重指数较高、糖尿病和身体虚弱相关（P<0.05）。在膝关节置换术前，循环GDF15水平与SPPB或PFS评分无关（P>0.05）。较高的基线循环GDF15水平与膝关节置换术后6个月SPPB评分的恢复呈负相关（P<0.05）。然而，在同一时间段内，基线循环GDF15水平与PFS评分的恢复之间没有显著关联（P>0.05）。在1个月或12个月的随访中，基线循环GDF15与SPPB或PFS评分的恢复之间没有显著关联（P>0.05）。这些发现表明，术前循环GDF15水平可能为全膝关节置换术后身体功能的恢复能力提供一些见解。有必要进一步研究以阐明GDF15与身体恢复力生物学之间的关系。
