Donor age and C1orf132/MIR29B2C determine age-related methylation signature of blood after allogeneic hematopoietic stem cell transplantation.
Level 4 - case-series / case-control
Small observational paired donor-recipient cohort study without a control group.
PubMed 27602173 · doi:10.1186/s13148-016-0257-7
What was done
DNA methylation across 32 CpG sites located in five age-associated genes (ELOVL2, C1orf132, TRIM59, KLF14, and FHL2) was measured via pyrosequencing in 16 donor-recipient pairs undergoing allogeneic hematopoietic stem cell transplantation (HSCT). DNA was isolated from donor whole blood collected shortly before HSCT and from recipient whole blood collected 27 to 360 days (mean 126 days) after transplantation. Epigenetic age predictions were compared against calendar and predicted ages of donors and recipients.
What was found
In recipients post-HSCT, predicted epigenetic age did not correlate with recipient calendar age, but strongly correlated with donor calendar age (r = 0.94, p = 4 × 10⁻⁸) and donor predicted age (r = 0.97, p = 5 × 10⁻¹⁰). Recipient predicted age was consistently lower than donor predicted age by 3.7 years (p = 7.8 × 10⁻⁴). This offset was driven by hypermethylation at C1orf132 CpGs (specifically C1orf132 CpG_1), and the recipient-donor methylation difference correlated with donor calendar age (r = 0.76, p = 6 × 10⁻⁴).
Why it matters
This confirms that recipient blood epigenetic age reflects the donor's age following allogeneic HSCT and identifies post-transplantation hypermethylation of C1orf132 (encoding MIR29B2C), suggesting a specific epigenetic signature linked to hematopoietic stem cell self-renewal after engraftment.
Limits
The study is limited by a small sample size (n = 16 pairs) and a wide post-transplant blood collection window (27 to 360 days). Blood cell subsets were not isolated or individually tested, and clinical graft outcomes were not evaluated.
Cited by
- supports Following hematopoietic stem cell transplantation, reconstituted blood retains the epigenetic age of the donor rather than the recipient for decades.