Evidence map›Paper›PMID 40684985›Full record

ReviewBiomedical journal2026

PAI-1 is a common driver of aging and diverse diseases.

Alireza Khoddam, Toshio Miyata, Douglas Vaughan

Abstract readReview
In one paragraph

Review in Biomedical journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

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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

3 authors.

Alireza KhoddamFeinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine Northwestern University, Chicago, USA. Electronic address: ali.khoddam@northwestern.edu.
Toshio MiyataTohoku University Graduate School of Medicine, Miyagi, Japan.
Douglas VaughanFeinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine Northwestern University, Chicago, USA.

Funding

Heterozygous SERPINE1 Deficiency Confers Durable Cardiovascular Fitness in HumansR35HL171553 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Douglas E Vaughan · 2024 to 2026
$3.3M
NHLBI NIH HHS R35 HL171553
6 · The paper itself

Abstract

Plasminogen activator inhibitor-1 (PAI-1) is a key driver of aging and contributes to diverse pathologies. This review examines PAI-1's multifaceted contributions to aging. At the cellular level, PAI-1 amplifies senescence, exhausts stem cell niches, and disrupts metabolism. These cellular alterations translate into physiological decline: PAI-1 drives cardiovascular aging by promoting vascular senescence and arterial stiffening, contributes to cognitive decline by impairing amyloid-beta clearance, fuels cancer progression through angiogenesis and immune suppression, and exacerbates muscle atrophy by hindering regeneration. A rare loss-of-function SERPINE1 mutation extends lifespan, illustrating how lifelong PAI-1 reduction can positively impact the human healthspan. Looking forward, targeting PAI-1 with inhibitors could mitigate senescence, restore stem cell function, improve metabolic profile, enhance physiological health, and promise a longer healthspan.

Indexed as

AgingPlasminogen Activator Inhibitor 1AnimalsHumansNeoplasmsPlasminogen Activator Inhibitor 1AgingCognitive declineMuscle atrophyPAI-1Senescence

Identifiers

PMID40684985
PMCPMC12859777

What OpenQuestion holds

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LicenceCC BY
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.