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Reversing age-associated arterial dysfunction: insight from preclinical models.

Venkateswara R Gogulamudi1, Jinjin Cai1, Lisa A Lesniewski1,2,3

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Journal of Applied Physiology (Bethesda, Md. : 1985)
|May 11, 2018
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Summary

Aging arteries contribute to cardiovascular disease (CVD). Calorie restriction (CR) benefits arterial function, and targeting energy-sensing pathways may offer similar vascular protective effects in older adults.

Keywords:
AMPKSIRT-1agingarterial stiffnesscalorie restrictionendothelial functioninflammationmTORoxidative stressvasodilation

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Area of Science:

  • Cardiovascular Science
  • Aging Research
  • Metabolic Pathways

Background:

  • Cardiovascular diseases (CVDs) are a leading cause of death, with aging as a primary risk factor.
  • Age-associated arterial dysfunction, characterized by impaired vasodilation and increased stiffness, is linked to oxidative stress and inflammation.
  • Calorie restriction (CR) extends lifespan and improves age-related conditions, including arterial dysfunction.

Purpose of the Study:

  • To review mechanisms of age-associated large artery dysfunction.
  • To discuss the impact of CR on these aging processes.
  • To explore energy-sensing pathways as potential targets for pharmacological calorie restriction mimetics to improve vascular health.

Main Methods:

  • Review of existing literature on aging, arterial function, CR, and energy-sensing pathways.
  • Discussion of the roles of mammalian target of rapamycin (mTOR), AMPK, and sirtuin-1 in CR's effects.
  • Analysis of evidence for targeting these pathways as vascular CR mimetics.

Main Results:

  • Aging leads to arterial dysfunction via oxidative stress and inflammation.
  • CR effectively mitigates age-associated arterial dysfunction.
  • Energy-sensing pathways (mTOR, AMPK, sirtuin-1) are implicated in CR's benefits, offering potential therapeutic targets.

Conclusions:

  • Targeting energy-sensing pathways may mimic CR's vascular benefits.
  • Pharmacological interventions modulating these pathways could combat age-related arterial dysfunction and reduce CVD risk in older individuals.