The hallmarks of aging framework was established by López-Otín and colleagues in a widely-cited 2013 Cell paper, and expanded to 12 hallmarks in a 2023 update (López-Otín, 2013; 2023). Applied to skin, each hallmark has specific, well-characterized manifestations.
The 12 hallmarks, in skin:
- Genomic instability — UV-induced DNA damage in keratinocytes, mutations accumulating in fibroblasts
- Telomere attrition — replicative senescence of fibroblasts and keratinocytes
- Epigenetic alterations — measurable via skin-specific methylation clocks
- Loss of proteostasis — damaged proteins accumulate; collagen glycation cross-links (AGEs)
- Disabled macroautophagy — impaired cellular cleanup contributes to senescence
- Deregulated nutrient sensing — mTOR/IGF-1 dysregulation; the insulin-IGF-1 axis is central to skin biology
- Mitochondrial dysfunction — reduced ATP for repair, increased ROS
- Cellular senescence — SASP-secreting fibroblasts drive skin aging; particularly relevant
- Stem cell exhaustion — hair follicle stem cells, dermal stem cells decline
- Altered intercellular communication — inflammaging; the systemic driver
- Chronic inflammation (2023 addition) — hs-CRP-driven MMP activity
- Dysbiosis (2023 addition) — microbiome contribution to skin aging via gut-skin axis
What's measurable on a well-designed panel: the JenSkin nine biomarkers map to several of these hallmarks directly — hs-CRP (chronic inflammation, altered communication), HbA1c and insulin (deregulated nutrient sensing, proteostasis loss via glycation), estradiol (intercellular communication in skin), vitamin D and zinc and B12 (proteostasis and stem cell function), omega-3 (intercellular communication, membrane function).
What's not on the panel but valuable for a comprehensive aging picture: epigenetic clocks (for epigenetic hallmark), senescent cell burden markers, telomere length.