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Two entirely different loci on the genome produce the same protein. Researchers have shown that expression of the senescence biomarker p21 is more nuanced than was previously thought. p21 is encoded by a gene known as Cdkn1a. However, this gene produces two transcripts which have not been equally well studied. To understand the contribution of each of these two transcripts, the researchers studied their relative expression in aged mice. The researchers found that only one of the transcripts - the less commonly studied version - is selectively elevated during aging. The researchers also checked how the different transcripts responded to senescence induced by genotoxic stress in cell cultures. This led to an increase in both transcripts, but with different dynamics. The more commonly studied one - which didn’t increase with age - went up immediately in response to genotoxic stress. The other version increased more slowly as the cells acquired senescent characteristics. That version was also more sensitive to treatment with the senolytic ABT-263 in mice. Altogether, this research shows that one of the transcripts produced by Cdkn1a is a more sensitive senescence biomarker than the other transcript or than p21 levels overall. This also clarifies our picture of p21, which may help us better understand its age-related functions.

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