Figure 2. Mechanistic links between shelterin proteins and other hallmarks of aging.

Dysfunctional shelterin protein regulation can induce genomic instability and telomere attrition, thereby contributing indirectly to cellular senescence and its byproducts: altered intercellular communication (e.g., inflammation) and exhaustion of stem cell populations. Shelterin proteins may also directly influence hallmarks of aging such as mitochondrial dysfunction, epigenetic alterations, and intercellular communication, likely alongside other unknown effects. Publications supporting such links are provided, but do not represent an exhaustive list. This figure was adapted from López-Otín et al., 2013, but note that an expanded list of hallmarks is included in López-Otín et al., 2023. References: ¹de Lange, 2018; ²Lim et al., 2021; ³Sharma et al., 2021; ⁴Wang et al., 2007; ⁵Mukherjee et al., 2018; ⁶Mukherjee et al., 2019; ⁷Stock et al., 2022; ⁸Chen et al., 2012; ⁹Zhu et al., 2019; ¹⁰Martínez & Blasco, 2010.