TY - JOUR
T1 - The 2010 ESPEN Sir David Cuthbertson Lecture
T2 - New and old proteins: Clinical implications
AU - McCoy, Rozalina G.
AU - Nair, K. Sreekumaran
N1 - Funding Information:
The manuscript was conceived by RGM and KSN, who also co-wrote the manuscript. The corresponding author (KSN) is the guarantor for the manuscript and takes responsibility for integrity of the data presented in the manuscript. The work is supported by RO1 DK41973 and RO1 AG09531 grants from the National Institutes of Health , the David Murdock – Dole Professorship, and institutional funds from the Mayo Clinic.
PY - 2013/10
Y1 - 2013/10
N2 - The past century had witnessed vast advances in biomedical research, particularly in the fields of genomics and proteomics, yet the translation of these discoveries into clinical practice has been hindered by gaps in mechanistic understanding of variability governing disease susceptibility and pathogenesis. Among the greatest challenges are the dynamic nature of the proteome and the imperfect methodologies currently available to study it. Here, we review key recently developed proteomic techniques that have allowed for dynamic characterization of protein quality, as well as quantity, and discuss their potential applications in understanding aging and metabolic disorders including diabetes. These methodologies revealed that senescence is characterized, in part, by decreased rates of de novo protein synthesis and potentially also degradation, in addition to concomitantly increased levels of oxidative stress, ultimately resulting in excessive accumulation of damaged and dysfunctional proteins. Insulin may be a key mediator in these pathologies, as hyperinsulinemia has been shown to hinder protein degradation while transient insulin deficiency may accelerate oxidative damage. We also discuss two interventions that have been proposed to delay, and possibly reverse, senescence by augmenting protein degradation: chronic caloric restriction and aerobic exercise.
AB - The past century had witnessed vast advances in biomedical research, particularly in the fields of genomics and proteomics, yet the translation of these discoveries into clinical practice has been hindered by gaps in mechanistic understanding of variability governing disease susceptibility and pathogenesis. Among the greatest challenges are the dynamic nature of the proteome and the imperfect methodologies currently available to study it. Here, we review key recently developed proteomic techniques that have allowed for dynamic characterization of protein quality, as well as quantity, and discuss their potential applications in understanding aging and metabolic disorders including diabetes. These methodologies revealed that senescence is characterized, in part, by decreased rates of de novo protein synthesis and potentially also degradation, in addition to concomitantly increased levels of oxidative stress, ultimately resulting in excessive accumulation of damaged and dysfunctional proteins. Insulin may be a key mediator in these pathologies, as hyperinsulinemia has been shown to hinder protein degradation while transient insulin deficiency may accelerate oxidative damage. We also discuss two interventions that have been proposed to delay, and possibly reverse, senescence by augmenting protein degradation: chronic caloric restriction and aerobic exercise.
KW - Aging
KW - Caloric restriction
KW - Proteomics
KW - Senescence
UR - http://www.scopus.com/inward/record.url?scp=84883559604&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883559604&partnerID=8YFLogxK
U2 - 10.1016/j.clnu.2012.12.015
DO - 10.1016/j.clnu.2012.12.015
M3 - Article
C2 - 23481224
AN - SCOPUS:84883559604
SN - 0261-5614
VL - 32
SP - 728
EP - 736
JO - Clinical Nutrition
JF - Clinical Nutrition
IS - 5
ER -