Genes and regeneration: Extending lifespan through gene transfer

Transferring regeneration-associated genes from simple organisms to complex animals could be a way to combat aging and enhance longevity.

In a study that has a hint of sci-fi about it, researchers from the University of Tokyo’s Graduate School of Pharmaceutical Sciences have reported on the intriguing possibility of extending lifespan through gene transfer. By borrowing genes from species known for their remarkable regenerative abilities – such as jellyfish and flatworms – the scientists aimed to investigate whether these genes could enhance the regenerative capacities and longevity of other organisms. While full regeneration is still more likely to be found on an episode of Doctor Who, the research of these other doctors marks a significant step towards understanding how genes linked to regeneration could potentially impact aging processes.

Longevity.Technology: Repairing damage is a therapeutic approach we often discuss, but the geroscientific implications of research into regeneration are profound, opening new doors to novel therapies that could delay or even reverse aspects of aging. By understanding and leveraging the biological mechanisms that drive aging, longevity researchers can develop interventions that improve healthspan, and by focusing on genes associated with high regenerative capacity, new strategies for maintaining stem cell function and tissue homeostasis can be found, enhancing the quality of life in aging populations.

In this study, the researchers introduced highly regenerative species-specific JmjC domain-encoding genes (HRJDs) into the common fruit fly, Drosophila melanogaster, a model organism with limited regenerative abilities. These HRJDs are a group of genes unique to animals capable of whole-body regeneration [1].

“In animals capable of whole-body regeneration, such as flatworms and jellyfish, specific genes may help allow regeneration and maintain long-term stem cell functions,” explained Associate Professor Yuichiro Nakajima, a leading researcher in the study. “Conversely, mammals and insects, which have limited regenerative abilities, may have lost these genes during evolution [2].”

The goal was to observe whether reintroducing these genes could have a beneficial effect on regeneration and aging processes in a species not typically known for its regenerative prowess.

The results were both surprising and promising; while the researchers initially hoped that the fruit flies might exhibit enhanced tissue regeneration, the reality was somewhat different. The introduction of HRJDs did not spur new tissue growth in injured flies, but an unexpected yet significant finding was observed in the intestinal stem cells of aging flies.

Hiroki Nagai, an expert in fruit fly intestines, discovered that HRJDs promoted greater division of intestinal stem cells while suppressing the differentiation errors that typically occur as these cells age [1].

“HRJDs promoted greater intestinal stem cell division, whilst also suppressing intestinal cells that were mis-differentiating, or going wrong in aged flies,” Nakajima noted [2]. This dual action is particularly noteworthy as it contrasts with traditional methods, such as the use of antibiotics, which might suppress the problematic cells but also hinder beneficial stem cell activity.

“For this reason, HRJDs had a measurable effect on the lifespans of fruit flies, which opens the door, or at least provides clues, for the development of new anti-aging strategies.” he added. “After all, human and insect intestines have surprisingly much in common on a cellular level [2].”

The implications of these findings are manifold – not only do they suggest a potential pathway for enhancing the health span of organisms, but they also raise questions about the fundamental mechanisms underlying regeneration and aging. The study revealed that the expression of HRJDs extended the lifespan of the fruit flies under non-regenerative conditions, specifically by enhancing the proliferative activity of intestinal stem cells while maintaining their differentiation fidelity [1]. This amelioration of age-related decline in gut barrier functions is a crucial insight, as it points to a potential method for preserving the integrity of vital tissues and organs in aging animals.

However, as with any pioneering research, there are both challenges and limitations. The aging process in fruit flies, though relatively quick compared with other animals, still spans approximately two months. This timeframe presented logistical challenges for the researchers, who had to juggle this study with other research. Moreover, while the current findings are promising, the precise molecular mechanisms by which HRJDs exert their effects remain largely unexplored.

The left two images show intestinal proteins disrupted by aging, and those on the right show the same proteins better preserved against age-related mechanisms due to the HRJD genes. ©2024 Hiroki Nagai CC-BY-ND

“Details of the molecular workings of HRJDs are still unresolved. And it’s unclear whether they work alone or in combination with some other component,” Nakajima admitted, highlighting the preliminary nature of this research.

Nonetheless, the study provides a valuable framework for future investigations. As Nakajima points out: “This is just the start of the journey, but we know now that our modified fruit flies can serve as a valuable resource to uncover unprecedented mechanisms of stem cell rejuvenation in the future [2].”

Given that human and insect intestines share notable similarities at the cellular level, the potential for translating these findings into human therapies is an exciting, albeit distant, prospect. The prospect of introducing regeneration-associated genes to combat aging and promote healthy lifespan is an enticing avenue of research that may one day lead to advances in regenerative medicine that are very much science fact.

[1] https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-024-01956-4

[2] https://www.u-tokyo.ac.jp/focus/en/press/z0508_00365.html