“In Vivo Partial Reprogramming Alters Age-Associated Molecular Changes during Physiological Aging in Mice”, Kristen C. Browder, Pradeep Reddy, Mako Yamamoto, Amin Haghani, Isabel Guillen Guillen, Sanjeeb Sahu, Chao Wang, Yosu Luque, Javier Prieto, Lei Shi, Kensaku Shojima, Tomoaki Hishida, Zijuan Lai, Qingling Li, Feroza K. Choudhury, Weng R. Wong, Yuxin Liang, Dewakar Sangaraju, Wendy Sandoval, Concepcion Rodriguez Esteban, Estrella Nuñez Delicado, Pedro Guillen Garcia, Michal Pawlak, Jason A. Vander Heiden, Steve Horvath, Heinrich Jasper, Juan Carlos Izpisua Belmonte2022-03-07 (epigenetics (aging))⁠:

Partial reprogramming by expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc) for short periods of time restores a youthful epigenetic signature to aging cells and extends the life span of a premature aging mouse model. However, the effects of longer-term partial reprogramming in physiologically aging wild-type mice are unknown.

Here, we performed various long-term partial reprogramming regimens, including different onset timings, during physiological aging.

Long-term partial reprogramming lead to rejuvenating effects in different tissues, such as the kidney and skin, and at the organismal level; duration of the treatment determined the extent of the beneficial effects. The rejuvenating effects were associated with a reversion of the epigenetic clock and metabolic and transcriptomic changes, including reduced expression of genes involved in the inflammation, senescence and stress response pathways.

Overall, our observations indicate that partial reprogramming protocols can be designed to be safe and effective in preventing age-related physiological changes. We further conclude that longer-term partial reprogramming regimens are more effective in delaying aging phenotypes than short-term reprogramming.

See Also:

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• Gene Therapy Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice

• Reversal of Aging via in Vivo Epigenetic Reprogramming

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• Sight restored by turning back the epigenetic clock: Neurons progressively deteriorate with age and lose resilience to injury. It emerges that treatment with three transcription factors can re-endow neurons in the mature eye with youthful characteristics and the capacity to regenerate.

• Longevity and rejuvenation effects of cell reprogramming are decoupled from loss of somatic identity

• Chemical reprogramming ameliorates cellular hallmarks of aging and extends lifespan

• Clock Work: Deconstructing the Epigenetic Clock Signals in Aging, Disease, and Reprogramming

• Many chronological aging clocks can be found throughout the epigenome: Implications for quantifying biological aging

• Current perspectives on the cellular and molecular features of epigenetic ageing

• Universal DNA methylation age across mammalian tissues

• Erosion of the Epigenetic Landscape and Loss of Cellular Identity as a Cause of Aging in Mammals

• Multi-omic rejuvenation and life span extension on exposure to youthful circulation [parabiosis]

• Heterochronic parabiosis reprograms the mouse brain transcriptome by shifting aging signatures in multiple cell types

• A cocktail of rapamycin, acarbose and phenylbutyrate prevents age-related cognitive decline in mice by altering aging pathways