Related Experiment Video

Updated: Sep 11, 2025

Evaluation of Injury-induced Senescence and In Vivo Reprogramming in the Skeletal Muscle
09:14

Evaluation of Injury-induced Senescence and In Vivo Reprogramming in the Skeletal Muscle

Published on: October 26, 2017

9.7K

Prevalent mesenchymal drift in aging and disease is reversed by partial reprogramming

Jinlong Y Lu1, William B Tu1, Ronghui Li2

  • 1San Diego Institute of Science, Altos Labs, San Diego, CA, USA.

Cell
|August 15, 2025
PubMed

Insights

Aging and disease involve loss of cell identity, characterized by "mesenchymal drift" (MD). Partial reprogramming rejuvenates cells by reducing MD, offering a new therapeutic strategy for age-related diseases.

Area of Science:

  • Cellular Biology
  • Aging Research
  • Genomics

Background:

  • Loss of cellular and tissue identity is a key feature of aging and disease.
  • Mechanisms driving this identity loss remain largely unknown.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying cellular identity loss in aging and disease.
  • To explore the potential of partial reprogramming as a therapeutic strategy.

Main Methods:

  • Analysis of gene expression data from over 40 human tissues and 20 diseases.
  • Investigation of "mesenchymal drift" (MD) and its correlation with disease progression.
  • Experimental suppression of key MD transcription factors.
  • Yamanaka factor-induced partial reprogramming to assess its impact on MD and epigenetic rejuvenation.

Main Results:

  • A pervasive upregulation of mesenchymal genes and altered stromal cell composition, termed "mesenchymal drift" (MD), was identified across multiple tissues and diseases.
  • Increased MD correlates with disease severity, reduced patient survival, and higher mortality risk.
  • Suppression of MD transcription factors induced epigenetic rejuvenation.
  • Partial reprogramming significantly reduced MD and rejuvenated the aging transcriptome without dedifferentiation.

Conclusions:

  • Mesenchymal drift is a significant factor in aging and disease progression.
  • Partial reprogramming offers a promising approach to reverse age-related cellular and tissue dysfunction by reducing MD.
  • These findings provide a mechanistic understanding of partial reprogramming's benefits and a framework for developing novel interventions.
Keywords:
Yamanaka factorsagingchronic kidney diseaseepithelial-mesenchymal transitionfibrosisheart failureidiopathic pulmonary fibrosismetabolic dysfunction-associated steatohepatitispartial reprogrammingrejuvenation

More Related Videos

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes09:16

Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes

Published on: June 3, 2018

7.4K
Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts09:29

Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts

Published on: March 22, 2017

7.5K

Related Concept Videos

Somatic to iPS Cell Reprogramming01:29

Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.3K
Forced Transdifferentiation01:28

Forced Transdifferentiation

Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial...
2.0K
Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
5.0K
Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.9K
Whole Body Regeneration01:33

Whole Body Regeneration

Regeneration is the process of restoring injured or lost tissues, organs, or body parts. While simpler organisms generally show greater ability to regenerate their whole body, few complex animals show similarly exceptional regeneration. For example, planarian flatworms have a unique regenerative potential making them a popular study organism among biologists to understand the mechanisms of whole body regeneration. Other organisms, such as hydra, also show extreme regeneration potential;...
3.4K