Cellular Rejuvenation Strategies

Cellular rejuvenation strategies aim to reverse age-related changes at the cellular level, addressing the gradual decline in organismal fitness that leads to tissue dysfunction and disease. These strategies focus on modulating key biological processes such as chromatin remodelling, stress response programs, and mitochondrial activity to restore cellular function and improve healthspan.

Partial Reprogramming

Partial reprogramming involves the limited induction of pluripotency factors without fully dedifferentiating cells into a pluripotent state. This approach has shown promise in reversing markers of aging, improving tissue repair capacity, and extending longevity in various models. For instance, the use of Yamanaka factors (OSKM) or a subset (OSK) has been demonstrated to reverse age-related changes and enhance health parameters in aged mice.

Maturation Phase Transient Reprogramming (MPTR)

MPTR is a method where reprogramming factors are expressed selectively until the rejuvenation point and then withdrawn. This technique has been shown to substantially rejuvenate cellular attributes, including the transcriptome and epigenome, in dermal fibroblasts from middle-aged donors.

Targeted Therapies for Thymic Involution

Age-related thymic involution contributes to immunosenescence and inflammaging. Strategies targeting the FOXN1-TEC axis, such as cellular therapy, cytokine therapy, and gene therapy, aim to restore thymic function and enhance T cell generation. Additionally, periphery-thymus axis therapies, including growth hormone supplementation and lifestyle interventions, show potential in mitigating thymic involution.

Epigenetic and Transcriptomic Rejuvenation

Techniques like partial reprogramming and MPTR have demonstrated the ability to reset epigenetic ageing clocks and rejuvenate the transcriptome, offering a pathway to separate rejuvenation from complete pluripotency reprogramming.

Challenges and Future Directions

While these strategies hold significant promise, challenges remain in evaluating complex processes like aging and ensuring the safety of interventions. Ongoing research is essential to fully understand the mechanisms and optimise rejuvenation strategies for therapeutic applications in aging and age-related diseases.