Role of endothelial NAD deficiency in age-related vascular dysfunction.

Authors:
Anna Csiszar
Anna Csiszar
New York Medical College
United States
Stefano Tarantini
Stefano Tarantini
University of Oklahoma Health Sciences Center
United States
Andriy Yabluchanskiy
Andriy Yabluchanskiy
The University of Texas Health Science Center
United States
Priya Balasubramanian
Priya Balasubramanian
The Ohio State University
United States
Tamas Kiss
Tamas Kiss
University of Westminster
United Kingdom
Eszter Farkas
Eszter Farkas
University of Szeged
Hungary
Joseph A Baur
Joseph A Baur
Harvard Medical School
United States
Zoltan Ungvari
Zoltan Ungvari
Reynolds Oklahoma Center on Aging

Am J Physiol Heart Circ Physiol 2019 Jun 15;316(6):H1253-H1266. Epub 2019 Mar 15.

Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma.

Age-related alterations in endothelium and the resulting vascular dysfunction critically contribute to a range of pathological conditions associated with old age. To develop therapies rationally that improve vascular health and thereby increase health span and life span in older adults, it will be essential to understand the cellular and molecular mechanisms contributing to vascular aging. Preclinical studies in model organisms demonstrate that NAD availability decreases with age in multiple tissues and that supplemental NAD precursors can ameliorate many age-related cellular impairments. Here, we provide a comprehensive overview of NAD-dependent pathways [including the NAD-using silent information regulator-2-like enzymes and poly(ADP-ribose) polymerase enzymes] and the potential consequences of endothelial NAD deficiency in vascular aging. The multifaceted vasoprotective effects of treatments that reverse the age-related decline in cellular NAD levels, as well as their potential limitations, are discussed. The preventive and therapeutic potential of NAD intermediates as effective, clinically relevant interventions in older adults at risk for ischemic heart disease, vascular cognitive impairment, and other common geriatric conditions and diseases that involve vascular pathologies (e.g., sarcopenia, frailty) are critically discussed. We propose that NAD precursors [e.g., nicotinamide (Nam) riboside, Nam mononucleotide, niacin] should be considered as critical components of combination therapies to slow the vascular aging process and increase cardiovascular health span.

Download full-text PDF

Source
https://www.physiology.org/doi/10.1152/ajpheart.00039.2019
Publisher Site
http://dx.doi.org/10.1152/ajpheart.00039.2019DOI Listing
June 2019
13 Reads

Publication Analysis

Top Keywords

vascular aging
12
health span
8
older adults
8
vascular dysfunction
8
nad deficiency
8
vascular
8
nad precursors
8
endothelial nad
8
nad
7
reverse age-related
4
age-related decline
4
decline cellular
4
treatments reverse
4
effects treatments
4
cellular nad
4
aging multifaceted
4
vasoprotective effects
4
multifaceted vasoprotective
4
limitations discussed
4
preventive therapeutic
4

Altmetric Statistics

References

(Supplied by CrossRef)

Similar Publications