Impact of Aging on Mitochondrial Respiration in Various Organs

Abstract

Mitochondria are considered central regulator of the aging process; however, majority of studies dealing with the impact of age on mitochondrial oxygen consumption focused on skeletal muscle concluding (although not uniformly) a general declining trend with advancing age. In addition, gender related differences in mitochondrial respiration have not been satisfactorily described yet. The aim of the present study was to evaluate mitochondrial oxygen consumption in various organs of aging male and female Fischer 344 rats at the ages of 6, 12 and 24 months. Mitochondrial respiration of homogenized (skeletal muscle, left and right heart ventricle, hippocampus, cerebellum, kidney cortex), gently mechanically permeabilized (liver) tissue or intact cells (platelets) was determined using high-resolution respirometry (oxygraphs O2k, Oroboros, Austria). The pattern of age-related changes differed in each tissue: in the skeletal muscle and kidney cortex of both sexes and in female heart, parameters of mitochondrial respiration significantly declined with age. Resting respiration of intact platelets displayed an increasing trend and it did not correlate with skeletal muscle respiratory states. In the heart of male rats and brain tissues of both sexes, respiratory states remained relatively stable over analyzed age categories with few exceptions of lower mitochondrial oxygen consumption at the age of 24 months. In the liver, OXPHOS capacity was higher in females than in males with either no difference between the ages of 6 and 24 months or even significant increase at the age of 24 months in the male rats. In conclusion, the results of our study indicate that the concept of general pattern of age-dependent decline in mitochondrial oxygen consumption across different organs and tissues could be misleading. Also, the statement of higher mitochondrial respiration in females seems to be conflicting, since the gender-related differences may vary with the tissue studied, combination of substrates used and might be better detectable at younger ages than in old animals.

Daily fluctuations in blood glucose with normal aging are inversely related to hippocampal synaptic mitochondrial proteins

“…Using a similar OXPHOS antibody cocktail as in the present study, one study reported lower protein content of Complex I subunit NDUFB8 and Complex IV subunit II MTCO2 in normally aging mice, but significantly greater level of Complex V subunit ATP synthase subunit alpha and no changes to Complex II subunit 30 kDa SDHB or Complex III subunit Core 2 UQCRC2 [56] . Lower levels of subunits that form ETC Complexes I and IV complement other data reporting lower enzyme activity of those complexes [57] , [58] , [59] , [60] . Mindful that contributions of Complexes I and IV may be especially consequential to brain aging, it bears mention that analyzing associations of blood glucose with OXPHOS subunits separately within age groups reduced the significance of all associations whereas the effect sizes of NDUFB8 and MTCO1 were largely unaffected, continuing to reflect medium-sized effects (i.e., r > 0.4) for both proteins in either age group.…”

Mitochondrial function in peripheral blood cells across the human lifespan

“…The sample size in the present study was 308, and the linear regression models allowed, in addition to examining the strength of the correlations, a quantification of the age effect. In a recent animal study with a large sample size, there was no decline in platelet respiratory function with age in 344 rats, even though such changes were seen in mitochondria from skeletal muscle and kidney cortex from the same rats 34 . We share the authors’ conclusion in that publication, further supported by the present findings, that one should be cautious not to generalize mitochondrial function across tissues.…”

Age-Dependent Alterations in Platelet Mitochondrial Respiration

“…Age dependence of mitochondrial function in various organs and brain regions in rats has been described [ 65 , 66 , 67 ]; the results did not confirm the concept of a general pattern of age-dependent mitochondrial dysfunction. No such data are available in humans; measurements in humans are usually performed using skeletal muscle biopsies, fibroblasts, and circulating blood cells [ 68 ].…”