In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice

Area of Science:

• Cellular biology
• Gerontology
• Epigenetics

Background:

• Partial reprogramming using Yamanaka factors (Oct4, Sox2, Klf4, c-Myc) can restore youthful epigenetic signatures and extend lifespan in premature aging models.
• The impact of long-term partial reprogramming on physiological aging in wild-type mice remains largely unexplored.

Purpose of the Study:

• To investigate the effects of various long-term partial reprogramming regimens on physiological aging in wild-type mice.
• To determine if extended partial reprogramming can induce rejuvenating effects and delay age-related changes.

Main Methods:

• Implementation of diverse long-term partial reprogramming protocols with varying onset timings in physiologically aging mice.
• Assessment of rejuvenating effects across multiple tissues (e.g., kidney, skin) and at the organismal level.
• Analysis of epigenetic clock reversion, metabolic profiles, and transcriptomic changes, focusing on inflammation, senescence, and stress response pathways.

Main Results:

• Long-term partial reprogramming demonstrated significant rejuvenating effects in various tissues and at the organismal level.
• The duration of partial reprogramming treatment directly correlated with the extent of beneficial anti-aging outcomes.
• Rejuvenation was associated with epigenetic clock reversal and reduced expression of genes linked to inflammation, senescence, and stress.

Conclusions:

• Partial reprogramming protocols can be safely and effectively designed to mitigate age-related physiological decline.
• Longer-term partial reprogramming regimens are more efficacious in delaying aging phenotypes compared to short-term interventions.
• This study highlights the potential of controlled, extended partial reprogramming as a strategy to combat aging.