DIETARY SUPPLEMENTATION WITH SPECIFIC AMINO ACID MIXTURES PROMOTES MITOCHONDRIAL BIOGENESIS: HYSIOLOGICAL AND PATHOPHYSIOLOGICAL RELEVANCE IN MAMMALS

Nutrients are major regulators of biochemistry and physiology
in living organisms, and subtle changes in nutrient
composition result in genetic or epigenetic control of processes
influencing healthspan and survival. Though contentious
Abstracts Ann Nutr Metab 2013;63(suppl 1):1–1960 99
yet, calorie restriction (the reduced intake of calories as foods
without malnutrition) postpones several age-related diseases,
hence extending healthspan and lifespan in many species.
The molecular basis of this long known phenomenon are still
elusive, albeit evidence seem to converge on the reduction of
mitochondria-derived oxidants through the generation of new,
more efficient organelles (mitochondrial biogenesis) (Nisoli et
al., Science 310: 314-317, 2005). Branched-chain amino acids
(BCAAs) display healthy effects both in animals and humans
(Valerio et al., Aging 3: 464-478, 2011). Notably, we reported
that unlike other amino acid mixtures, a BCAA-enriched mixture
(BCAAem), promoted mitochondrial biogenesis in cultured
cardiomyocytes and skeletal myocytes as well as in heart
and skeletal muscles of sedentary and trained middle-aged
mice. This was accompanied by muscle fiber rejuvenation,
improved locomotor activity and coordination, and extension
of average lifespan (D´Antona et al., Cell Metab 12: 362-372,
2010), suggesting that BCAAem acts as a CR mimetic. We then
investigated the BCAAem effects on statin-induced muscle damage
in mice. Though known to be rather safe, statin use is
associated with an elevated risk of myopathy, ranging in severity
from asymptomatic increases in creatine kinase to muscle
weakness, aches and fatigue, up to the rare fatal rhabdomyolysis.
We found that BCAAem prevented atorvastatin- and
rosuvastatin-induced structural and functional deterioration
of skeletal muscles in both wild-type and hypercolesterolemic
mice (ApoE receptor knockout mice on a high-fat diet).
Statin prescription is expected to grow alongside the aging of
population. Dietary supplementation with specific amino acid
mixtures may be an effective strategy to avoid common adverse
effects limiting the adherence to statin therapy in human subjects.