Pulse 114: Anti-Aging from Worm Experiments to Human Therapies

12 August 2019
Giulio Prisco

Nematode

A protein known as LIN-53 has been found to play an important role in healthy aging (see below), in nematode worms. LIN-53 affects muscle development through the molecular complex NuRD, while it affects lifespan through a separate complex, Sin3. The fact that these are distinct pathways, but both involving LIN-53, is particularly intriguing and strongly suggests the importance of LIN-53 as a link between healthspan and lifespan. Since the protein is very similar to human protein RBBP4/7, the insights gained from worm studies could, one day, find clinical applications in human patients.

"It is such a small organism and yet still resembles human tissues, pathways and gene regulation, so we are able to transfer results from the nematode to humans," said lead researcher Stefanie Müthel.

I guess Müthel means something like “we might eventually be able to transfer ...” In fact, the road from lab experiments with worms to working anti-aging therapies for humans is likely to be long. Yet, this and similar research results are encouraging.

Protein has powerful anti-aging effects in worms. Researchers at the Max Delbrueck Center for Molecular Medicine (MDC) have identified an epigenetic mechanism that appears to strongly influence healthy aging. A study published in Aging Cell reveals that the protein LIN-53, which controls muscle integrity, lifespan and levels of an essential sugar, plays an important anti-aging role in worms, ensuring muscle development and longer life.

New drug could improve chemotherapy for pancreatic cancer. Scientists at Columbia University have suggested that a new drug, able to penetrate the protective barrier around pancreatic cancers and accumulate in malignant cells, might improve current chemotherapy. The drug, an experimental compound called PTC596, is known to have antitumor activity in mouse and human pancreatic cancer cells. The scientists have tested PTC596 in combination with gemcitabine (a first-line drug for pancreatic cancer) in genetically engineered mice with an aggressive form of pancreatic cancer that is generally resistant to chemotherapy. The results, described in a study published in Clinical Cancer Research, are encouraging.

DNA methylation preserves molecular memory in fish. University of Otago researchers have found that molecular memory, in the form of “DNA methylation,” is preserved between generations of fish, in contrast to humans where it is almost entirely erased. DNA methylation encodes additional information passed from parents to their offspring, which we are only starting to understand. In humans and other mammals, DNA methylation is erased at each generation. But the new research results, outlined in a study published in Nature Communications, show that global erasure of DNA methylation memory does not occur in fish.

Biodegradable implants for precise, controlled release of painkillers. EPFL researchers have developed biodegradable microresonators, described in a study published in Advanced Functional Materials, which can be heated locally with a wireless system. The device could be used in implants to control the release of painkillers within tissue. Such an implant would enable release of controlled amounts of anesthetic in a specific location over several days. After that, the implant will degrade safely inside the body.

Toward cancer therapies with minimal side effects. Scientists at Oregon State University, University of Central Florida, and New York University, have advanced toward new cancer therapies that don't have the side effects that often accompany many current cancer treatments by identifying a protein modification that specifically supports survival of tumor cells. The research results, published in Journal of Biological Chemistry, outline a new therapeutic strategy for the treatment of tumors of the nervous system, with minimal to no side effects on normal tissues.

Nano-vaccine effective against melanoma in laboratory mice. Researchers at Tel Aviv University have developed a novel nano-vaccine for melanoma, the most aggressive type of skin cancer. Their approach, described in a research paper published in Nature Nanotechnology, has so far proven effective in preventing the development of melanoma in mouse models and in treating primary tumors and metastases that result from melanoma.

Immunotherapy for treatment-resistant lymphoma. Mount Sinai researchers have developed a way to use immunotherapy drugs against treatment-resistant non-Hodgkin's lymphomas for the first time by combining them with stem cell transplantation. According to the researchers this approach, described in a paper published in Cancer Discovery, could also dramatically increase the success of the drugs in treatment of melanoma and lung cancer.

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