Reversing age by reprogramming gene expression networks in skin cells

Good news! We are getting closer to the fountain of youth! 

SRSF1 (Serine/Arginine-Rich Splicing Factor 1)

"... In the study ..., the team first developed a novel age predictor. Specifically, they designed a machine learning algorithm trained on gene expression (transcriptomic) profiles across multiple aging processes in human skin fibroblast cells spanning a wide age range. This predictor accurately pinpointed the “transcriptomic age” of skin cells obtained from several donors.

Leveraging this age predictor as a scorable readout then enabled the team to screen a focused collection of genes that were predicted to affect aging processes in one way or another. The goal was to identify candidates that, when over-expressed, could shift the originally assigned aging score of old fibroblast cell lines to a more youthful score.

The top-scoring gene, encoding an RNA processing factor known as SRSF1, was indeed able to reduce features that corresponded to several hallmarks of aging, such as a biological process where damaged cells stop dividing but do not die (cellular senescence), disruptions in the normal balance and turnover of proteins (proteostatic stress), and chronic low-grade inflammation (also dubbed “inflammaging”).

Importantly, when delivered to aged mice, where it primarily accumulated in the liver, SRSF1 reduced the animals’ rate of aging and extended their lifespan by 14%, highlighting SRSF1 as a “geroprotective” target.  ...

The most prominent role of SRSF1 is that of an “RNA splicing factor” that helps include protein-coding, so-called alternative exon sequences in a subset of mature messenger RNA molecules (mRNAs). These can then be translated by protein-synthesizing ribosomes into proteins, many of which have altered functions. ..."

Reversing age by reprogramming gene expression networks "Aging-specific screening platform identifies gene with multifaceted rejuvenation potential that extends health- and lifespan in mice"