Progerin expression in humans: Implications for natural ageing.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic and observational literature without systematic review methodology.
PubMed 41780574 · doi:10.1016/j.mad.2026.112164
What was done
This narrative review synthesizes literature on the expression of progerin—a truncated lamin A isoform that causes Hutchinson-Gilford Progeria Syndrome—in physiological human aging. The authors examine its tissue-specific presence (notably in skin, vasculature, and blood cells), mechanistic contributions to cellular senescence, endogenous modulators, and its feasibility as a clinical biomarker.
What was found
The abstract reports qualitative mechanistic relationships and contains no numerical data. Low-level progerin expression in non-syndromic tissues is associated with nuclear deformation, chromatin disorganization, DNA damage, telomere attrition, mitochondrial stress, stem cell exhaustion, and premature senescence. The review notes that endogenous factors such as WRN helicase and telomere-protective mechanisms buffer against this nuclear lamina stress.
Why it matters
The paper frames progerin as a shared biological driver between accelerated genetic progeria and normal human aging, suggesting it could serve as a tissue-specific biomarker for vascular and dermal aging when paired with systemic measures like epigenetic clocks.
Limits
As a narrative review, the paper provides no new empirical data, meta-analytic pooling, or protocolized study selection. Practical application is currently constrained by progerin's very low abundance in normal tissues, tissue specificity, and the lack of validated ultrasensitive assays and longitudinal human studies.
Cited by
- supports Healthy humans produce small amounts of progerin, and its levels increase during normal aging.