NIH grant: Recovery, EPigenetics And Inflammaging Research after critical illness (REPAIR-ICU) (1R35GM166313-01)

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NIH grant 1R35GM166313-01: Recovery, EPigenetics And Inflammaging Research after critical illness (REPAIR-ICU)
Institute: {'code': 'GM', 'abbreviation': 'NIGMS', 'name': 'National Institute of General Medical Sciences', 'admin_org_id': '12500024', 'admin_funding_url': ''}. PI: Florian  Mayr. Award: $388768.
Start: 2026-08-15T00:00:00.
PROJECT ABSTRACT
Each year, more than 5.7 million Americans survive intensive care only to face months to years of frailty,
cognitive decline, recurrent hospitalizations, and premature death. These outcomes are not random sequelae
of critical illness but reflect the activation of conserved aging programs (e.g., telomere attrition, mitochondrial
dysfunction, cellular senescence, and inflammaging) that persist long after discharge. Post-ICU recovery,
therefore, represents a human model of stress-accelerated aging: abruptly triggered, measurable, and
potentially reversible, offering a tractable setting to study mechanisms and test interventions.
Over the past five years, my laboratory has shifted its focus from population-level epidemiology to biologically
grounded recovery science. We demonstrated that ICU survivors experience accelerated immune aging and
persistent inflammation, with biomarker trajectories that predict late mortality and recurrent hospitalization. In
large patient datasets, we defined discrete recovery trajectories, anchored in the concept of allostatic overload,
that identify early, time-sensitive windows when outcomes diverge. Building on this foundation, we have
established the infrastructure—ongoing cohort enrollment, targeted assays, and analytic pipelines—needed to
interrogate senotype biology. Our toolkit now includes DNA methylation clocks, telomere length, curated panels
of the senescence-associated secretory phenotype (SASP), and immune-exhaustion markers, paired with
remote monitoring of heart rate variability, sleep, and activity. These capabilities provide the readiness to move
from descriptive signals to mechanistic tests of causation.
The proposed REPAIR-ICU (Recovery, Epigenetics, and Inflammaging Research after Critical Illness) program
will integrate three thrusts: (1) map stress-accelerated senotypes across blood and multi-omic platforms; (2)
capture their digital fingerprint using low-burden remote monitoring; and (3) identify and prioritize causal,
targetable pathways for intervention. This work will be anchored in an ongoing single-center cohort and
complemented by new prospective enrollment of ICU survivors at UPMC and the VA. The MIRA mechanism is
ideally suited to sustain this program, as it provides the flexibility to pursue emergent biology, adapt as new
tools emerge, and test multiple therapeutic avenues. By reframing survivorship as stress-accelerated aging,
REPAIR-ICU will deliver biologically grounded recovery pathways, advancing the science of post-ICU care
toward interventions that extend healthspan and resilience beyond the hospital door.

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