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"

Getting under the skin of psoriasis

Good news! Amazing stuff! This study combines two of the latest technologies!

"... an ionic liquid (IL) combination to successfully deliver a small interfering RNA (siRNA)-based treatment directly to the skin in a mouse model of psoriasis, significantly reducing levels of inflammatory cytokines and symptoms of psoriasis without systemic side effects. ..."

"... However, effective delivery of small interfering RNA (siRNA) into the skin is a substantial hurdle due to skin’s barrier function and poor stability of siRNA. Using ionic liquids as an enabling technology, we report on the effective delivery of NFKBIZ siRNA into the skin and its therapeutic efficacy in a psoriasis model. Treatment with IL-siRNA suppressed aberrant gene expression and resulted in down-regulation of psoriasis-related signals including TNF-α and IL-17A. These results provide a framework for a topical delivery platform for siRNA."

Getting under the skin of psoriasis Ionic-liquid-based technology delivers RNA therapeutic to locally block psoriasis-associated genes in mice

Here is the link to the research paper: Treatment of psoriasis with NFKBIZ siRNA using topical ionic liquid formulations

Bone marrow-on-a-chip models damage and disease

Recently, I blogged here about body-on-a-chip!  Now, a new organ-on-a chip has been reported! Amazing stuff!

"Until David Chou, Viktoras Frismantas and their colleagues developed the bone marrow chip, the only way to study living marrow tissue effectively was to take painful biopsies from the bones. ... we are in a position to assist in the design of human clinical trials for rare genetic disorders and advance personalized medicine in ways not possible before"

Bone marrow-on-a-chip models damage and disease – Physics World: Human bone marrow chip provides a reliable model to study bone marrow damage by radiation, drugs and disease

A probiotic therapy for patients with inflammatory bowel disease

Good news!

"Now, a research team ... has developed a living-material approach that uses a strain of genetically engineered E.coli Nissle gut bacteria as a locally acting probiotic. The engineered bacteria produce a network of nanofibers that directly binds to mucus to fill inflamed areas like a patch, shielding them from gut microbes and environmental factors. ... “The Probiotic Associated Therapeutic Curli Hybrids (PATCH) approach, as we named it, creates a biocompatible, mucoadhesive coating that functions as a stable, self-regenerating Band-Aid and provides biological cues for mucosal healing.”"

A probiotic therapy for patients with inflammatory bowel disease – Harvard Gazette: A genetically programmed living hydrogel material that facilitates intestinal wound healing is being considered for development as a probiotic therapy for patients with inflammatory bowel disease.