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Study · Animal study (in vivo) · mouse · 2023

4 results

Targeting mitochondria in the aged cerebral vasculature with SS-31, a proteomic study of brain microvessels.

Seman A, Chandra PK, Byrum SD, Mackintosh SG, Gies AJ, Busija DW, Rutkai I

GeroScience17 Jul 2023Cited by 11 (Europe PMC)

Summary

Cognitive impairment and dementias during aging such as Alzheimer's disease are linked to functional decline and structural alterations of the brain microvasculature. Although mechanisms leading to microvascular changes during aging are not clear, loss of mitochondria, and reduced efficiency of remaining mitochondria appear to play a major role. Pharmacological agents, such as SS-31, which target mitochondria have been shown to be effective during aging and diseases; however, the benefit to mitochondrial- and non-mitochondrial proteins in the brain microvasculature has not been examined. We tested whether attenuation of aging-associated changes in the brain microvascular proteome via targeting mitochondria represents a therapeutic option for the aging brain. We used aged male (> 18 months) C57Bl6/J mice treated with a mitochondria-targeted tetrapeptide, SS-31, or vehicle saline. Cerebral blood flow (CBF) was determined using laser speckle imaging during a 2-week treatment period. Then, isolated cortical microvessels (MVs) composed of end arterioles, capillaries, and venules were used for Orbitrap Eclipse Tribrid mass spectrometry. CBF was similar among the groups, whereas bioinformatic analysis revealed substantial differences in protein abundance of cortical MVs between SS-31 and vehicle. We identified 6267 proteins, of which 12% were mitochondria-associated. Of this 12%, 107 were significantly differentially expressed and were associated with oxidative phosphorylation, metabolism, the antioxidant defense system, or mitochondrial dynamics. Administration of SS-31 affected many non-mitochondrial proteins. Our findings suggest that mitochondria in the microvasculature represent a therapeutic target in the aging brain, and widespread changes in the proteome may underlie the rejuvenating actions of SS-31 in aging.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In aged mice, cerebral blood flow was similar between SS‑31 and vehicle groups.

    In plain wordsIn aged mice, brain blood flow was similar with SS‑31 and with vehicle.

    Outcome
    No significant changeCerebral blood flow
    Study

    mousen: not reported in source

    Aged C57Bl6/J mice
    Comparator
    Vehicle saline
    Outcome group
    Aging markers · Nervous system and cognition
    Studied dose
    Dose not stated · 2 weeksAs given in this study (mouse).

    Source sentences

    Summary
    CBF was similar among the groups
    1 context sentence
    Summary · context
    We used aged male (> 18 months) C57Bl6/J mice treated with a mitochondria-targeted tetrapeptide, SS-31, or vehicle saline.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In aged mice, SS‑31 treatment caused substantial differences in protein abundance of cortical microvessels compared with vehicle.

    In plain wordsIn aged mice, SS‑31 changed the amounts of many proteins in small brain blood vessels compared with vehicle.

    Outcome
    MixedCortical microvessel protein abundance
    Study

    mousen: not reported in source

    Aged C57Bl6/J mice
    Comparator
    Vehicle saline
    Outcome group
    Aging markers · Nervous system and cognition
    Studied dose
    Dose not stated · 2 weeksAs given in this study (mouse).

    Source sentences

    Summary
    whereas bioinformatic analysis revealed substantial differences in protein abundance of cortical MVs between SS-31 and vehicle.
    1 context sentence
    Summary · context
    We used aged male (> 18 months) C57Bl6/J mice treated with a mitochondria-targeted tetrapeptide, SS-31, or vehicle saline.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In aged mice, 107 of the mitochondria-associated proteins in cortical microvessels were significantly differentially expressed between SS‑31 and vehicle.

    In plain wordsIn aged mice, SS‑31 changed the levels of 107 mitochondrial proteins in small brain blood vessels compared with vehicle.

    Outcome
    MixedMitochondria-associated protein expression in cortical microvessels
    Study

    mousen: not reported in source

    Aged C57Bl6/J mice
    Comparator
    Vehicle saline
    Outcome group
    Mitochondrial function · Nervous system and cognition
    Studied dose
    Dose not stated · 2 weeksAs given in this study (mouse).

    Measurements

    Differentially expressed mitochondria-associated proteins
    107 proteins
    SS-31 vs vehicle

    Source sentences

    Summary
    We identified 6267 proteins, of which 12% were mitochondria-associated. Of this 12%, 107 were significantly differentially expressed and were associated with oxidative phosphorylation, metabolism, the antioxidant defense system, or mitochondrial dynamics.
    1 context sentence
    Summary · context
    We used aged male (> 18 months) C57Bl6/J mice treated with a mitochondria-targeted tetrapeptide, SS-31, or vehicle saline.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In aged mice, SS‑31 administration affected many non-mitochondrial proteins in cortical microvessels.

    In plain wordsIn aged mice, SS‑31 also changed the levels of many proteins that are not part of mitochondria.

    Outcome
    MixedNon-mitochondrial protein expression in cortical microvessels
    Study

    mousen: not reported in source

    Aged C57Bl6/J mice
    Comparator
    Vehicle saline
    Outcome group
    Aging markers · Nervous system and cognition
    Studied dose
    Dose not stated · 2 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Administration of SS-31 affected many non-mitochondrial proteins.
    1 context sentence
    Summary · context
    We used aged male (> 18 months) C57Bl6/J mice treated with a mitochondria-targeted tetrapeptide, SS-31, or vehicle saline.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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