In aging, the vulnerability of rat brain mitochondria is enhanced due to reduced level of 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNP) and subsequently increased permeability transition in brain mitochondria in old animals

•Aging is accompanied by progressive dysfunction of mitochondria.•Increased mitochondrial permeability transition pore (mPTP) activity leads to cell death.•Brain mitochondria from aged animals have increased mPTP opening.•2′, 3′–Cyclic nucleotide 3′–phosphodiesterase (CNP) regulates mPTP.•In aging the diminished CNP level leads to mitochondrial dysfunction. Aging is accompanied by progressive dysfunction of mitochondria associated with a continuous decrease of their capacity to produce ATP. Mitochondria isolated from brain of aged animals show an increased mitochondrial permeability transition pore (mPTP) opening. We recently detected new regulators of mPTP function in brain mitochondria, the enzyme 2′, 3′–cyclic nucleotide 3′–phosphodiesterase (CNP) and its substrates 2′, 3′–cAMP and 2′, 3′–cNADP, and the neuronal protein p42IP4. Here, we compared parameters of mPTP opening in non-synaptic brain mitochondria isolated from young and old rats. In mitochondria from old rats (>18 months), mPTP opening occurred at a lower threshold of Ca2+ concentration than in mitochondria from young rats (