Endurance exercise as a countermeasure for aging.
OBJECTIVE
We determined whether reduced insulin sensitivity, mitochondrial dysfunction, and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity.


METHODS
Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young (18-30 years old) and older (59-76 years old) subjects. Expression of proteins involved in fuel metabolism was measured by mass spectrometry. Citrate synthase activity, mitochondrial DNA (mtDNA) abundance, and expression of nuclear-encoded transcription factors for mitochondrial biogenesis were measured. SIRT3, a mitochondrial sirtuin linked to lifespan-enhancing effects of caloric restriction, was measured by immunoblot.


RESULTS
Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older subjects, but no age effect was noted. Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals. Although endurance-trained individuals exhibited higher expression of mitochondrial proteins, mtDNA, and mitochondrial transcription factors, there were persisting effects of age. SIRT3 expression was lower with age in sedentary but equally elevated regardless of age in endurance-trained individuals.


CONCLUSIONS
The results demonstrate that reduced insulin sensitivity is likely related to changes in adiposity and to physical inactivity rather than being an inevitable consequence of aging. The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction, although there are persisting effects of age on mtDNA abundance and expression of nuclear transcription factors and mitochondrial protein. Furthermore, exercise may promote longevity through pathways common to effects of caloric restriction.
Lanza
Ian R
IR
Division of Endocrinology, Endocrinology Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Short
Daniel K
DK
Short
Kevin R
KR
Raghavakaimal
Sreekumar
S
Basu
Rita
R
Joyner
Michael J
MJ
McConnell
Joseph P
JP
Nair
K Sreekumaran
KS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D015153:Blotting, Western; D004272:DNA, Mitochondrial / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D010807:Physical Endurance / Q000502:physiology*; D040901:Proteomics; D056566:Sirtuin 3; D037761:Sirtuins / Q000378:metabolism; D055815:Young Adult
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C525046:Sirt3 protein, mouse; D056566:Sirtuin 3; D037761:Sirtuins