Joon-Hyuk Lee

Ph.D. in neuroscience. Former GPF fellow, @wonsukchung lab. Currently @HFSP postdoc fellow, @QuintanalabHMS in Harvard Medical School

[John Lukens @LukensJohnR]

C1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain @ScienceMagazine https://t.co/OZoKApeIeF

[Assoc. Prof. Tim Sargeant @TimSargeant1]

This is a really important paper for the #autophagy field - impairment of #cognitive ability and motor performance in mice caused by reduced autophagy (thought to occur during aging in the brain) can be restored when autophagy is rescued - it's reversible: https://t.co/17M0Jsf0vW

[Pluchino lab - Regenerative Neuroimmunology @Pluchinolab]

The multiple scales of astrocytic functional units https://t.co/5NE20Sc9OI

[IdoAmitLab @IdoAmitLab]

For those of you who think macrophages do almost everything, rethink “almost.”
They are programmable cells, recruited into whatever new function evolution needs.
https://t.co/tz6VrVQWpw

[Arc Institute @arcinstitute]

The brain works hard to clear waste, and impairments are central to neurodegeneration. In @CellCellPress, Innovation Investigator @andcyang, w/ @NaliniRRao, Yuichi Chayama, and team map it from the inside out, following the brain's own proteins to see where waste actually goes.

[David Sinclair @davidasinclair]

New paper @Nature analyzing 11,000 profiles of cellular gene expression provides further evidence that aging is not just wear & tear but a reversible loss of epigenetic information linked directly to mortality risk

Reprogramming, embryogenesis & young blood partially reversed aging signals. Why is this important?

The work implies that the youthful state of tissues is not lost permanently during aging.

It can be restored

The work is also the strongest systems-level support yet for the idea that aging is not just random wear and tear, but a coordinated and reversible loss of biological information.

In many ways, it strengthens the Information Theory of Aging (ITOA), which we first formulated back in 2008-2009.

The striking thing is not simply that damage accumulates. It is that cells enter a coordinated transcriptional state associated with mortality risk, which strongly argues aging is an organized systems phenomenon. This is exactly what you would expect if cells progressively lose youthful epigenetic control information.

The work by the Gladyshev lab @harvardmed (no link to us) suggests aging is not a collection of unrelated damage. It behaves more like an attractor state.Cells under many forms of stress drift toward a common aged configuration.

That is deeply compatible with the idea that epigenetic information loss causes cells to progressively collapse due to informational noise. We call this process epigenetic drift, leading to ex-differentiation.

One of the most important aspects is that it links aging directly to mortality risk rather than simply chronological time. Prof Gladyshev and team developed transcriptomic clocks that don’t just estimate age, they measure the progressive loss of cellular function and predict biological decline and mortality risk across mammals.

That is a major advance because it brings us closer to measuring the underlying process of aging itself, not just the passage of time, in a way first shown by Prof. Steven Horvath in 2013.

The team also launched TACO (Transcriptomic Age Calculator Online) allowing researchers to estimate the biological age and mortality risk of tissues using RNA data they may already have. A potentially powerful new tool for aging research

What I find especially important is that the strongest mortality-associated changes involve chromatin organization, epigenetic regulation, inflammation, and mitochondrial dysfunction.

These are all deeply connected to the maintenance of cellular identity and the preservation of biological information over time.

The study strongly supports the idea that aging is not merely the accumulation of damage, but a progressive loss of the systems that maintain youthful cellular organization.

In many ways, this aligns with the Information Theory of Aging, which proposes that cells lose epigenetic information over time but retain a backup copy that can potentially be restored.

Importantly, the paper also confirms that these molecular signatures are reversible, which we and others have previously shown.

They accelerate after DNA damage, and during disease and stress, but slow or reverse during interventions such as reprogramming, heterochronic parabiosis, and early embryogenesis.

That gives real hope that aging is biologically malleable & perhaps, one day, medically treatable 🙏

Thanks for reading all the way down. I gave this whole analysis to a reporter and my quote was 2 words: "Major advance" 😆

So we can all stay abreast of this fast paced field, @JoinLifespan has a new show & a magazine written by real scientists. As a community we are sponsoring young scientists, too. Maybe check us out 🙏

[Eric Topol @EricTopol]

A small randomized trial in patients with metastatic pancreatic cancer found benefit for paricalcitol, a Vitamin D analog https://t.co/CDnIwm0xeo
Good @salkinstitute explainer https://t.co/QgEKHiquIa

[Jonathan Kipnis 🟦 @jonykipnis]

All you needed to know about sleep, brain clearance and dementia in this important and beautifully written review by Maiken Nedergaard || The oscillatory biology of sleep: Linkage to dementia | Science https://t.co/xvubhNgLX3

[BryanRoth @zenbrainest]

Cool!
Dopamine drives persistent remodelling of the maternal brain
https://t.co/sYiaCUVlcu

[Eric Topol @EricTopol]

The way to maintain a healthy brain without neurodegenerative disease may be through the immune system. Sharp essay on the crosstalk between the immune system and brain, and how to leverage that to prevent Alzheimer's disease @ScienceTM https://t.co/U1QbRbHezl

[Andrea Salvador @amsalvador1]

https://t.co/mRZf138F7k innervation prevents tumor TLO formation and makes tumors cold?? 👀👀👀

[Brian S. Kim @itchdoctor]

We resubmitted this paper a week ago. This paper has been up on preprint for a year now while in revision. There is uniform consensus that this is a very big concept. There is (as always will be) debate as to how throughly we have proven the existence of these polyorganic neurons that have been brought up for decades. However, a huge advantage of the preprint process is that it gives time for others to replicate or even find orthogonal motifs that support our claims. We now know that many labs have either prospectively found these or retrospectively found them in their datasets (serious labs). We also know there are motifs in other parts of the nervous system that mirror what we found, discovered by others. Astute patients have reached out saying they truly feel this is why they have visceral pain (some of them world class scientists). This, to me, is the beauty of science and the preprint process. We do not validate through replication from a single process, assay, or lab. We crowdsource the science and let time ferment the truth out through external validation. Congrats @ZhennWang! This is one way in which DeSci comes alive. Many more to come. @RHubJournal @ResearchHub @ResearchHubF @researchsquare

https://t.co/tZT808wUkx

[John Lukens @LukensJohnR]

Maternal high-fat diet drives sex-specific microglia remodeling of serotonergic reward circuits https://t.co/2syoSBRdpF

[John Lukens @LukensJohnR]

Aged circulating CD8+ T cells and their secreted factors drive cognitive decline https://t.co/Ih6QYtmNri
@ImmunityCP

[Andrea Salvador @amsalvador1]

https://t.co/uyc4ecZFP4 -> maternal adaptation in the gut provides innate defense to protect offspring and mother 👀

[Andrea Salvador @amsalvador1]

https://t.co/FpACyIpjS1 -> organ specific ECM shapes identities of intrinsic nervous systems. v cool!

[Roychoudhuri Lab @RoychoudhuriLab]

Incredible new paper from Max Krummel's group showing that macrophages sample cellular content from living cells to present to T cells! https://t.co/fcZBiyw41D

[Jonathan Kipnis 🟦 @jonykipnis]

Very exciting work from Antoine Louveau’s lab on how macrophages prune meningeal lymphatics|| Macrophage-mediated refinement of the dural lymphatic regulates social behavior: Neuron https://t.co/jPUVocFUnN

[Pluchino lab - Regenerative Neuroimmunology @Pluchinolab]

🧠 New research from @ThoraKaradottir's team (I also see many other friends there!) shows focal white matter lesions don't just cause local damage — they actively drive neuroinflammation and synapse loss across multiple brain circuits

https://t.co/3kOu9rAo85

[Ali Max Erturk @erturklab]

Just out in @Nature: using iDISCO tissue clearing and whole-brain 3D imaging, the authors show that astrocytes form large-scale, structured networks connecting specific brain regions via gap junctions. These networks span hemispheres, show striking regional specificity, and dynamically remodel, revealing a new layer of brain connectivity beyond classical neuronal circuits.

Work by the @LiddelowSA and Moses V. Chao labs (NYU):

https://t.co/WIh5DCgjuj

#DISCO #Clearing #3DImaging