Single Muscle Fiber Proteomics Reveals Fiber-Type-Specific Features of Human Muscle Aging

TY - JOUR

T1 - Single Muscle Fiber Proteomics Reveals Fiber-Type-Specific Features of Human Muscle Aging

AU - Murgia, Marta

AU - Toniolo, Luana

AU - Nagaraj, Nagarjuna

AU - Ciciliot, Stefano

AU - Vindigni, Vincenzo

AU - Schiaffino, Stefano

AU - Reggiani, Carlo

AU - Mann, Matthias

N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2017/6/13

Y1 - 2017/6/13

N2 - Skeletal muscle is a key tissue in human aging, which affects different muscle fiber types unequally. We developed a highly sensitive single muscle fiber proteomics workflow to study human aging and show that the senescence of slow and fast muscle fibers is characterized by diverging metabolic and protein quality control adaptations. Whereas mitochondrial content declines with aging in both fiber types, glycolysis and glycogen metabolism are upregulated in slow but downregulated in fast muscle fibers. Aging mitochondria decrease expression of the redox enzyme monoamine oxidase A. Slow fibers upregulate a subset of actin and myosin chaperones, whereas an opposite change happens in fast fibers. These changes in metabolism and sarcomere quality control may be related to the ability of slow, but not fast, muscle fibers to maintain their mass during aging. We conclude that single muscle fiber analysis by proteomics can elucidate pathophysiology in a sub-type-specific manner.

AB - Skeletal muscle is a key tissue in human aging, which affects different muscle fiber types unequally. We developed a highly sensitive single muscle fiber proteomics workflow to study human aging and show that the senescence of slow and fast muscle fibers is characterized by diverging metabolic and protein quality control adaptations. Whereas mitochondrial content declines with aging in both fiber types, glycolysis and glycogen metabolism are upregulated in slow but downregulated in fast muscle fibers. Aging mitochondria decrease expression of the redox enzyme monoamine oxidase A. Slow fibers upregulate a subset of actin and myosin chaperones, whereas an opposite change happens in fast fibers. These changes in metabolism and sarcomere quality control may be related to the ability of slow, but not fast, muscle fibers to maintain their mass during aging. We conclude that single muscle fiber analysis by proteomics can elucidate pathophysiology in a sub-type-specific manner.

KW - Journal Article

U2 - 10.1016/j.celrep.2017.05.054

DO - 10.1016/j.celrep.2017.05.054

M3 - Journal article

C2 - 28614723

SN - 2639-1856

VL - 19

SP - 2396

EP - 2409

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -