iiinova — where your digital self keeps evolving

Alberto Sanz @albertosanzmon1.bsky.social · 27/06/2026

Latest publication from Mario Cordero's lab: NLRP3 haploinsufficiency unmasks a compensatory NLRP1-NLRP3 interaction that drives accelerated aging in mice | Science Advances www.science.org/doi/10.1126/... with a modest contribution from yours truly ;-)

science.org

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Reposted by Alberto Sanz

Mike Murphy @mitoredox.bsky.social · 30/01/2026

Funding? I'm a simple academic, so I'll have to await someone smart to explain to me how "pausing" MRC and BBSRC funding is the action of a biomedical science superpower...?

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Reposted by Alberto Sanz

Anthony Dornan @dornan.bsky.social · 23/12/2025

A welcome finish to what has been, & continues to be, a rough year. Proud to have been a (small) part of this work published in @elife.bsky.social, which, as always from the Dobson Lab, is meticulous, thorough & insightful.

doi.org

Microbiota impact Drosophila ageing via Acetobacter, Tachykinin, and TkR99D

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Alberto Sanz @albertosanzmon1.bsky.social · 17/12/2025

PhD studentship at @glasgow.ac.uk #Mitochondria × #spectroscopy × #machinelearning. Detect mitochondrial defects, estimate age, and identify anti-ageing drugs across species. Supervisors: @albertosanzmon1.bsky.social @mariogonzalez.es & @nealdawson.bsky.social UK Home fees only. shorturl.at/wvMQa

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Reposted by Alberto Sanz

Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

We have updated a previous preprint from our laboratory, and after two additional years of experiments, we now present new findings that fundamentally reshape how we—meaning us, not necessarily everyone—understand ageing. www.biorxiv.org/content/10.1...

biorxiv.org

Developmental Programming of Mitochondrial Function Limits Lifespan in Short-Lived Animals

The contribution of mitochondria to lifespan determination remains controversial, as impaired mitochondrial function can paradoxically both shorten and extend longevity. During ageing, mitochondria ac...

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Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

Are flies good models for ageing? Absolutely—perhaps not perfect for human ageing, though. However, if we want to extend radically human lifespan, we will need to succeed first in “simpler” animals, worms and flies.

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Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

Many questions remain. Other multiprotein complexes may follow the same developmental “set-and-freeze” logic.

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Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

In short: • Development sets mitochondrial capacity • Early dysfunction permanently limits lifespan • Adult flies cannot rebuild or remodel OXPHOS (or their capacity is very limited)

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Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

Thus, OXPHOS levels are fixed during development because they are difficult to replace, and short-lived organisms avoid doing so—trading longevity for reproductive efficiency.

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Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

We believe this reflects evolutionary logic: in short-lived animals, there is no point investing in adult mitochondrial repair. They must reproduce quickly, leaving no time for extensive turnover...

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Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

Here’s the twist: adult mitochondria cannot rebuild their respiratory chain. OXPHOS proteins have exceptionally long half-lives; RNAi in adults fails to reduce respiration, and adult-only rescue cannot restore it. The OXPHOS system is fixed for life at eclosion.

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Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

Crucially, this misprogramming can be corrected—but only during development. Partial restoration of mitochondrial function (AOX) or metabolic rewiring (Rheb) in development rescues lipid homeostasis, restores autophagy balance and dramatically extends adult lifespan. Timing is everything.

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Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

Why does this window matter so much? Because early mitochondrial dysfunction misprogrammes adult physiology. Flies show chronic starvation signalling, disrupted proteostasis and overwhelmed autophagy—even though adult respiration looks similar in short- and long-lived CIV-depleted flies.

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Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

Impair Complex IV during development and flies die dramatically earlier. Apply the same impairment only in adulthood (really late in development), and the effect is modest, even though both groups carry “aged-like” mitochondria that produce more ROS per ATP generated.

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Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

We’ve uncovered a fundamental mechanism explaining why short-lived animals are so short-lived. In Drosophila, mitochondrial respiratory capacity is set during development—and once fixed, cannot be rebuilt in adulthood. This developmental programming imposes a hard limit on lifespan.

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Alberto Sanz @albertosanzmon1.bsky.social · 07/12/2025

biorxiv.org

Developmental Programming of Mitochondrial Function Limits Lifespan in Short-Lived Animals

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Alberto Sanz @albertosanzmon1.bsky.social · 06/11/2025

Excellent work, Payam! Congratulations to you and the entire team on this insightful paper!

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Reposted by Alberto Sanz

Alessandro Prigione @aleprigio.bsky.social · 19/05/2025

Exciting news! Our most important work is out as preprint! We suggest sildenafil as a treatment for mitochondrial disease Leigh syndrome, from stem and organoid model to mice and off-label use. Next step is the clinical trial starting early next year! www.medrxiv.org/content/10.1...

medrxiv.org

Pluripotent stem cell-based drug discovery uncovers sildenafil as a treatment for mitochondrial disease

Mitochondrial disease encompasses inherited disorders affecting mitochondrial function. A severe and untreatable form of mitochondrial disease is Leigh syndrome (LS) causing psychomotor regression and...

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Alberto Sanz @albertosanzmon1.bsky.social · 23/03/2025

A podcast discussing our paper on the role of CI on aging and mitochondrial disease: www.youtube.com/watch?v=Usu7...

youtube.com

Timing Mitochondrial Dysfunction: The Key to Regulating Aging

YouTube video by Science Sanz Hub

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Alberto Sanz @albertosanzmon1.bsky.social · 23/03/2025

Thanks to the paper's first author, @rhodophila , all our collaborators, and Wellcome and BBSRC, among others, for funding this study.

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Alberto Sanz @albertosanzmon1.bsky.social · 23/03/2025

Finally, it's too early to know if this happens in humans. If it does, early treatment of mitochondrial disease is crucial. If not, we must learn how adult flies cope with minimal CI and apply that knowledge to #humans.

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Alberto Sanz @albertosanzmon1.bsky.social · 23/03/2025

#Omics analysis reveals differences between short- and long-lived individuals. These can be explored to identify which features of CI depletion are pathogenic (found only in short-lived flies) and which are not (found in long-lived flies).

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Alberto Sanz @albertosanzmon1.bsky.social · 23/03/2025

Our results identify development as the critical stage where CI must function optimally, while age-related CI reduction in activity may act as an anti-ageing adaptation.

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Alberto Sanz @albertosanzmon1.bsky.social · 23/03/2025

If we massively reduce CI levels only in adult flies, they do not live shorter but instead live longer than controls. Notably, this depletion exceeds the levels observed in aged flies and is comparable to the reduction seen in individuals suffering from #mitochondrialdisease.

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Alberto Sanz @albertosanzmon1.bsky.social · 23/03/2025

During development, a small disruption of mitochondrial #ComplexI (CI) in #Drosophila enormously shortens adult lifespan. This disruption falls within the natural variability in mitochondrial respiration observed among wild-type strains.

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