Ben Doughty

Update3.

Still trying to think of what to call it..

The Soft-in-the-Head Hypothesis
The Jelly Head Model
The Waterworld Hypothesis (great movie)
osf.io/sd5g4/wiki?w...

The molecular basis of force selectivity by PIEZO2 Nature - PIEZO2 is intrinsically more rigid than PIEZO1, and disparate mechanical stimuli paradoxically evoke opposite conformational and gating responses in each channel.

New paper from the lab led by @ericmulhall.bsky.social addresses how PIEZO1 and PIEZO2 are tuned to different types mechanical forces. From nanometer-scale super-resolution microscopy to in vivo experiments, links single-molecule observations to physiological function.
www.nature.com/articles/s41...

Autism researchers rebuke Kennedy, form independent advisory group A group of autism researchers and advocates are forming an independent advisory body to develop a scientific agenda for the autism community.

nice move to counter pseudoscience
www.statnews.com/2026/03/03/a...

Metabolic shift → ECM change?

Cardiomyocyte hypertrophy co-localizes with accumulation of hyaluronan in cMyBPC+/- mice hearts
www.biorxiv.org/content/10.6...

If I'm the opposite will I make it?

good morning everyone project your personal imposter syndrome onto this gif ur welcome

pity them

What about people who are not US citizens? most of their userbase seems to be non-US. I asked in his AMA, no response..
#ChatGPT

Integrins sense stiffness by pulling on the ECM.
HMW-HA increases hydration and alters matrix viscoelasticity.
Does changing HA content change how much force cells actually “feel”?

It’s time for #moleratmonday, where we bring you a fun fact about the naked mole rat, and it’s also Monday 🐀 Today’s fact:

For a rodent, they have an incredibly long lifespan. It’s estimated to be ~10 years in the wild, and 30+ in captivity! The price: they’re super wrinkly even when they’re young

I think its called: Hyperreality

If glycolytic ATP production declines with age, some tissues may rely more on mitochondrial respiration, increasing ROS exposure. Since the hexosamine pathway branches from glycolysis, reduced flux could theoretically alter UDP-sugar availability and extracellular matrix dynamics.

The Right Chemistry: There are lots of longevity regimens. One stands out for me Amid an explosion of aging research, there are plenty of “biohackers” out there jumping the gun without waiting for proof of efficacy.

"and has even infused himself with blood from his son. While he sleeps, Johnson wears a device that measures nighttime erections which he believes to be a measure of cardiovascular health."

montrealgazette.com/opinion/colu...

Oral sodium hyaluronate improves skin hydration, barrier function and signs of aging: a randomized, double-blind, placebo-controlled trial in 150 healthy adults - Scientific Reports Scientific Reports - Oral sodium hyaluronate improves skin hydration, barrier function and signs of aging: a randomized, double-blind, placebo-controlled trial in 150 healthy adults

Interesting result given that orally administered HA is likely degraded in the gut before absorption. It would be interesting to know whether absorbed fragments are large enough to have signalling effects, or whether most of it is recycled into normal sugar pools.
www.nature.com/articles/s41...

Hyaluronidases as Targets for the Treatment of Neurological Diseases Hyaluronan (HA) is a glycosaminoglycan synthesized at the cell membrane that can exist in numerous states in the extracellular matrix, including in ternary complexes with proteoglycans such as aggrecan and neurocan. HA synthesis is elevated ...

HA catabolism is highly regulated with approximately a third (5 g) of the body’s total HA content turning over each day.

"Hyaluronidases as Targets for the Treatment of Neurological Diseases."
pmc.ncbi.nlm.nih.gov/articles/PMC...

When they say a baby has low birth weight are they always smaller? Could less HMW-HA reduce mass because HA binds water and contributes to tissue volume

"Assemble the Board of Peace - I'm starting a war".

If I ever somehow manage to get this into a preprint (unlikely, I’m still learning), I’m calling it:

Neo(teny) in the Matrix
or
The Wet Soil Hypothesis
or
The Inflammaturation Model
osf.io/sd5g4/wiki?w...
Updated:

Post a pic you took, no context, to bring some zen to the feed.

New preprint with Léo Pio-Lopez:
www.preprints.org/manuscript/2...

"Multi-Scale Longevity: Defeating Aging from Cells to Embodied Human Minds, and the Future of the Species"

a broader view of longevity research.

If I ever somehow manage to get this into a preprint (unlikely, I’m still learning), I’m calling it:

Neo(teny) in the Matrix
osf.io/sd5g4/wiki?w...

Alpha-Gal syndrome ⤵️🟡 sad #glycotime 😞

This is the same as the menstrual cycle isn't it? except if no pregnancy occurs it switches back to HIF-1a. Seems to also be the same with gestation.
What may be possible is oxygen levels or pseudohypoxia reverting the tissue back to the inflammatory phase.
Also interesting: Estrogen driving HAS2

Proliferative / Angiogenic Phase (Day 3–10)
Oxygen improves
HIF-1a declines
HIF-2a stabilizes (>5% 02)
More HMW-HA, less LMW-HA

Inflammatory Phase (Hours–3 Days)
Fibroblasts upregulate HAS2 - massive increase
HMW-HA increase but ROS + hyaluronidases cleave it into LMW-HA
LMW-HA amplifies inflammation

What really interests me is HIF signalling in development and wound healing

Wound healing:
Initial tissue damage (Minutes–Hours)
HIF-1α stabilizes(<5% 02)
HIF-2α minimal
Some LMW-HA appear

Hymecromone Promotes Longevity and Insulin Sensitivity in Mice - PubMed Given that the extracellular matrix polymer hyaluronan (HA) has been implicated in longevity, we asked whether 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, impacts lifespan in mice. We designed a prospective study of long-term administration of 4-MU with conventional C57BL/6J mice. We …

Inhibiting HAS with hymecromone extends lifespan. Long-term treatment still leaves many tissues with normal HMW. Authors suggest compensation may boost HAS2, and that longevity may come from reducing LMW fragments rather than total HA.
pubmed.ncbi.nlm.nih.gov/39451245/

I didn’t realize the retina contains PNN-like ECM components. Visual development shifts toward more stable foveal detail over childhood. If humans evolved extended neoteny, could that prolong global-dominant processing? Might faster maturation bias earlier detail dominance?

I wonder whether the same mechanism could be relevant in neurodevelopmental disorders and preeclampsia.

Frontiers | Dysregulated hyaluronan metabolism drives inflammation and angiogenesis in proliferative diabetic retinopathy PurposeTo investigate the expression levels of enzymes and receptors of the hyaluronan (HA) pathway, including HA synthase (HAS)-2, hyaluronidase (Hyal)-1, H...

This feels like a clear example of how ECM fragmentation can lock tissue into a chronic wound state. If HA size distribution regulates inflammatory tone, dysregulated HA turnover may act as a central amplifier in metabolic disease.
www.frontiersin.org/journals/imm...