July 9th, 2024

New insights into transcription factors and chromatin remodeling

Researchers at the University of Queensland reveal insights on aging control mechanisms, focusing on transcription factors and chromatin remodeling. AP-1 plays a key role in gene regulation, offering potential for age-related disease interventions and healthspan enhancement.

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New insights into transcription factors and chromatin remodeling

Researchers from the University of Queensland have uncovered new insights into the master controller of aging and development, shedding light on the molecular mechanisms underlying these processes. The study, published in Cell Metabolism, focused on transcription factors and chromatin remodeling, revealing common pathways governing the transition from youth to old age. Led by Dr. Christian Nefzger, the research identified a distinct transcription factor binding site signature shared between developmental and aging processes, with AP-1 emerging as a pivotal regulator in activating adult genes while dampening early-life genes. This discovery has significant implications for addressing age-related diseases like Alzheimer's and metabolic disorders. By targeting AP-1 and its associated pathways, researchers aim to develop interventions that can extend quality of life and potentially prevent the onset of these diseases. The ultimate goal is to enhance healthspan, the period of life spent in good health, by understanding and addressing the fundamental processes driving aging at the molecular level. Future research is expected to explore additional transcription factors and regulatory elements to pave the way for innovative therapeutic approaches in geriatric medicine.

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Link Icon 15 comments
By @jbandela1 - 6 months
> “By pinpointing AP-1 as a master controller linked to aging across cell types, we can now study the effects of drugs that reduce its activity to extend quality of life,” he said [2]. Targeting AP-1 and its associated pathways could lead to interventions that slow down or even prevent the onset of these diseases, marking a significant advancement in geriatric medicine.

Unfortunately, AP-1 is also involved in cancer.

From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361657/

> Activator protein-1 (AP-1) is a transcription factor that consists of a diverse group of members including Jun, Fos, Maf, and ATF. AP-1 involves a number of processes such as proliferation, migration, and invasion in cells. Dysfunctional AP-1 activity is associated with cancer initiation, development, invasion, migration and drug resistance.

Mentioning AP-1 without mentioning its role in cancer is misleading. Many of the mechanisms that are involved with aging, likely have a role with controlling cancer by keeping cells, especially cells with damage, from proliferating or invading nearby or distant tissue.

By @personalityson - 6 months
One step closer to longevity escape velocity
By @boznz - 6 months
In my sixties and If longevity of life comes with full cognitive and physical health for the individual so they can continue contributing to society, then I'm all in. Otherwise what is the point, I will just be a burden on the world and reduced to a market for big pharma and big health care to get richer and the economy to get poorer as health care spending increases.

I guess these are hard questions for everyone and I don't want individuals reduced to a number in a dataset but mankind has certainly gotten itself in a bit of a pickle.

By @begueradj - 6 months
It's strange that mitochondria is not mentioned in this article. For a long time, it was believed to play a paramount role in aging.
By @Unbefleckt - 6 months
I'm sure I read about this in New Scientist maybe 12 years ago? They found this "switch" and turned it off in mice. We basically age and die so that we don't have denisovans running around mating with people who have hundreds of thousands of years of adaptations that have been tried and tested, but you can just turn that feature off. Right?
By @1propionyl - 6 months
Unfortunately this site doesn't work properly with blockers enabled and redirect cycles. Unfortunately, won't be reading.
By @swayvil - 6 months
It's like the world is some kind of clockwork. Or computer. Or a field of barley? What metaphor are we using these days?
By @vikramkr - 6 months
Edit: Thanks to whoever changed the title for the post!

jfc the media telephone chain here is absurd. "Revealing a master controller of development and ageing" becomes "AP-1: The Master Regulator." A -> the is a pretty big jump. (https://www.uq.edu.au/news/article/2024/06/revealing-master-...)

Also - ugh these content mills are so lame. The university PR departments aren't helping - why a university feels it needs to contribute to lowering public trust in science by claiming every paper is a generation defining breakthrough is beyond me. But maybe pause for a second before breathlessly passing along a headline like 'master controller of aging and development uncovered'? And the underlying research (https://www.sciencedirect.com/science/article/pii/S155041312...) and techniques used etc is pretty interesting - please don't cut research funding to genetics a few years down the line when immortality fails to materialize like longevity.whatever promised.

By @grishka - 6 months
I wonder how this fits together with heterochronic parabiosis.
By @tomrod - 6 months
... In mice.. And human! cells.

From the paper:

• Multi-omic analysis of maturation and aging across >45 mouse and human cell types

• Common transcription factor pattern for chromatin remodeling in maturation and aging

• Encoded via relative abundance of AP-1, CTCF, and cell identity factor binding sites

• Remodeling mechanism activated by AP-1, stress, systemic factor, or PRC2 inhibition

By @eointierney - 6 months
Having worked in cancer hospitals at the age of 16 (35 years ago) and having a father a doctor who coordinated long term cancer treatment in our country, I can say that cancer treatment has come on in leaps and bounds. What was once a death sentence is now likely treatable, and more treatments are coming online almost by the day. We will never beat cancer as we will never beat death, but we can prolong life, prevent pain, and always make sickness easier to bear both for those who suffer it and their loved ones.

C'mon the Science!

By @fifteen1506 - 6 months
Oh great, everyone in positions of power will be Biden-like. That bodes well for society.
By @gcp123 - 6 months
The gist of it in plain english:

1. Our genes change as we age with some becoming more active, while others become less active.

2. The researchers found a special protein called AP-1 that acts like a master switch. As we get older, AP-1 becomes more active.

3. AP-1 turns on "adult" genes and turns down "young" genes. This happens in many different types of cells in our body.

4. These changes in gene activity are linked to the aging process and may explain why we experience age-related health issues.

5. Understanding this process could help scientists develop new ways to prevent or treat diseases that commonly affect older people, like Alzheimer's or diabetes.