Aging accelerates in transplant patients with older organs

Alzheimer's polygenic risk scores tied to different processes based on cell type.

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In organ transplants, older donors often provide organs to younger recipients. As cells age, they can stop multiplying and release harmful chemicals, affecting nearby cells. Older organs tend to have more aged, non-multiplying cells, which can harm transplant outcomes.

Researchers from Brigham and Women’s Hospital studied this in mice. They found that transplanting older organs into younger mice caused issues. The younger mice had lower physical abilities, like reduced running and grip strength. They also showed signs of anxiety, memory problems, and learning difficulties. This suggests that using older organs in transplants negatively affects the recipients.

The study showed that when older organs were transplanted into younger recipients, it sped up aging effects. This happened because the older transplants released certain aging-related substances and mitochondrial DNA. Treating the older donor mice with drugs that inhibit aging before taking out the organs helped reduce the aging symptoms in the recipient mice.

Principal investigator Stefan G. Tullius, MD, Ph.D., of the Division of Transplant Surgery, said, “Currently, due to insufficient supply in clinical organ transplantation, donor and recipient ages differ substantially. Our results suggest that senolytic treatments can be a potential therapeutic approach for improving the outcomes of older organs.”

Creating treatments for Alzheimer’s disease (AD) is challenging because various cells in the brain contribute to the disorder through complex mechanisms. Microglia and astrocytes, immune and support cells in the central nervous system, express genes linked to AD risk, especially AD dementia. However, it wasn’t clear how and when these genetic risk factors influenced different stages of AD progression, such as the build-up of amyloid-β plaques and tau tangles.

Brigham and Women’s Hospital researchers studied the impact of AD genetic risk specific to each significant brain cell type on key disease processes. They used advanced techniques to analyze genetic risk scores from large clinical research datasets. 

By examining autopsy data and neuroimaging from preclinical AD stages, they discovered that astrocyte-specific genetic risk was linked to earlier stages, like amyloid-β accumulation. In contrast, microglia-specific risk played a role in later stages involving plaque and tau tangle build-up and cognitive decline.

Hyun-Sik Yang, MD, of the Department of Neurology, said, “Our results provide human evidence for how genetic risk in specific brain cells affects AD processes, some even before the onset of clinical symptoms. Future studies could extend our technique to other aspects of AD or other diseases to help develop targeted treatments.”

In conclusion, the study found that using older organs in transplants can make recipients age faster. Knowing how this happens allows us to create treatments that can make organ transplants more successful, especially when using older organs. However, more research and tests in hospitals may be needed to be sure about these findings and to find ways to help people who get organ transplants age more slowly.

Journal reference:

  1. Yang, HS., Teng, L., Kang, D. et al. Cell-type-specific Alzheimer’s disease polygenic risk scores are associated with distinct disease processes in Alzheimer’s disease. Nature Communication. DOI: 10.1038/s41467-023-43132-2.

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