Evidence map›Paper›PMID 42012729›Full record

ReviewMolecular biology reports2026

Spermidine in the aging brain: mechanisms, preclinical evidence, and clinical perspectives.

Sergio Pandolfi, Geir Björklund, Charlye Ghezzi, Francesco Maria Paone, Salvatore Chirumbolo

Abstract readReview
PubMed Publisher
In one paragraph

Review in Molecular biology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Sergio PandolfiHigh Master School of Oxygen-Ozone Therapy, University of Pavia, Pavia, Italy.
Geir BjörklundCouncil for Nutritional and Environmental Medicine, Mo i Rana, Norway.
Charlye GhezziCouncil for Nutritional and Environmental Medicine, Mo i Rana, Norway.
Francesco Maria PaoneUnit of Paediatrics, University Hospital "Tor Vergata", Rome, Italy.
Salvatore ChirumboloDepartment of Engineering for Innovation Medicine, University of Verona, Strada Le Grazie 8, Verona, 37134, Italy. salvatore.chirumbolo@univr.it.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spermidine, a naturally occurring polyamine, has emerged as a candidate modulator of brain aging because it regulates autophagy, mitochondrial function, oxidative balance, and neuroinflammatory signaling. This review summarizes current knowledge on spermidine biology, including its synthesis, catabolism, transport, and cell-specific handling in neurons and glia, with emphasis on ATP13A2/ATP13A4-dependent trafficking and EP300-linked autophagy. Preclinical studies consistently show that spermidine enhances proteostasis, reduces soluble amyloid-beta, improves microglial phagocytic activity, preserves mitochondrial fitness, and attenuates inflammatory responses in models of aging and neurodegeneration. Human evidence is encouraging but still limited: observational studies associate higher dietary spermidine intake with better cognitive outcomes, whereas interventional trials suggest possible benefits in subjective cognitive decline and mild dementia, with variable dose-dependent effects. Overall, spermidine is a biologically plausible nutraceutical for healthy brain aging, but larger, well-designed clinical trials are needed to define efficacy, bioavailability, safety, and optimal therapeutic use across prodromal, early-stage, and disease-specific patient populations.

Indexed as

AgingBrainSpermidineAnimalsAutophagyHumansMitochondriaNeuronsSpermidineaging brainAlzheimer’s diseasehealthy agingneurodegenerativeParkinson’s diseasepolyaminesspermidine

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.