Calabria 2017 MiP2017

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Elisa Calabria
Age and frailty related changes in PBMCs mitochondrial function and whole body physiology.

Link: MiP2017

Calabria E, de Jong V, Tarperi C, Gelati M, Salvagno GL, Lippi G, Schena F (2017)

Event: MiP2017

COST Action MITOEAGLE
Aging is associated to the progressive decline of physiological functions related to physical activity, cardio-respiratory function, cognitive capacities and immunity. All this is accompanied by reduced mobility, or viceversa, and often leads to changes in the quality of life and health. Frailty is a further condition that is also associated with aging, however the information linking aging, frailty and mitochondrial bioenergetics are still unclear. It has been proposed that progressive mitochondrial dys-function with increased accumulation of oxidative stress could be at the basis of the aging process [1]. Comparing two groups of healthy men of different age, we have shown that healthy aging is associated with the down-regulation of a set of genes associated with the mitochondrial electron transport system in blood cells [2]. Recent studies indicate that the measurement of mitochondrial function in human blood cells is associated with the level of fitness [3].

To untangle the links existing between human aging, frailty, physical activity and mitochondrial function we are evaluating whole body physiological parameters and mitochondrial respiratory capacity in blood cells (PBMCs) in three groups of 10 volunteers (men and women) of different ages (40, 70 and 80 years old). We collected data of physical performance (SPPB test), cardio-respiratory capacity (VO2peak; HR), strength of upper and lower limbs, and mitochondrial function with in vivo high-resolution respirometry (HRR) on PBMCs. Data collected show the well known age-relate decline of VO2peak (p=0.001; r=-0.632), but also strength and physical performance parameters are negatively associated with age.

The values of mitochondrial respiration (FCR) related to ETS supported by complex II (ETS_cII) are significantly reduced in the most aged group (80s). ETS coupling efficiency (1-L/E) is significantly lower (-13%) in men versus women in the 70s groups (p 0.03). ETS_cII resulted also to be negatively associated with the % of body fat (%BFAT) (p 0.038; r -0.417). The values of leak respiration following cell permeabilization resulted positively associated with VO2peak.

In conclusion the results reported are still preliminary, but it is interesting to observe that PBMCs mitochondrial function and efficiency is modulated by aging and gender. Although mitochondrial oxygen consumption is evaluated in circulating PBMCs, our data support the idea that metabolic adaptations occurring in blood cells are reflecting systemic metabolic properties, and the association between the ETS_cII and LEAK dissipative respiration with measures of body composition and whole body oxygen consumption point in this direction.


Bioblast editor: Kandolf G O2k-Network Lab: IT Verona Calabria E


Labels: MiParea: Respiration, Gender  Pathology: Aging;senescence 

Organism: Human  Tissue;cell: Blood cells  Preparation: Permeabilized cells 


Coupling state: LEAK, ET  Pathway:HRR: Oxygraph-2k 


Affiliations

Dept Neurosciences, Biomedicine Movement Sciences. - elisa.calabria@univr.it

References

  1. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300.
  2. Tyrrell DJ, Bharadwaj MS, Van Horn CG, Marsh AP, Nicklas BJ, Molina AJ (2015) Blood-cell bioenergetics are associated with physical function and inflammation in overweight/obese older adults. Experimental Gerontology 70:84-91.
  3. Calabria E, Mazza EM, Dyar KA, Pogliaghi S, Bruseghini P, Morandi C, Salvagno GL, Gelati M, Guidi GC, Bicciato S, Schiaffino S, Schena F, Capelli C (2016) Aging: a portrait from gene expression profile in blood cells. Aging 8:1802-21.