Table 1.

Alterations of the aging molecular mechanisms (pillars) in DS

Aging pillars	DS phenotype
Metabolism	↑ mTOR pathway activation (Di Domenico et al., 2018) ↑ oxidative stress (Garlet et al.., 2013; Valenti, Manente, Moro, Marra, & Vacca, 2011) ↑ mitochondrial dysfunction (Conte et al., 2018; Helguera et al., 2013) widespread age‐related deregulation of red blood cell metabolism (Culp‐Hill et al., 2013)
Stem cells and regeneration	↓ self‐renewal of stem cells (Adorno et al., 2013; Cairney et al., 2009)
Macromolecular damage	↑ oxidative damage (Cenini et al., 2012; Franceschi et al., 1992) ↑ sensitivity to DNA damaging agents (Morawiec et al., 2008)
Inflammation	↑ chronic inflammation (Zhang et al., 2017) ↑ accumulation of immune cells with memory phenotype (Cossarizza et al., 1990, 1991)
Adaptation to stress	↑ difficulties to cope with increased proteomic stressors (Aivazidis et al., 2017)
Proteostasis	↓ proteostasis (Aivazidis et al., 2017; Di Domenico et al., 2013)
Epigenetics	Age‐related changes in epigenetic machinery (Ciccarone et al., 2018) ↑ DNA methylation age (Horvath et al., 2015)