Low expression of CD39 and CD73 genes in centenarians compared with octogenarians

Crooke, Almudena; Martínez-Henández, Juan; Martínez‐López, Joaquín; Cruz-Jentoft, Alfonso J.; Huete-Toral, Fernando; Pintor, Jesús

doi:10.1186/s12979-017-0094-3

Cited by 7 publications

(7 citation statements)

References 28 publications

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“…Increased mRNA expression of CD73 has also been described in blood cells of older adults (>79 years old) when compared with young and middle‐aged adults (Crooke et al . ). All together these results suggest that in ageing an increased SNAP25 expression will be associated with an increased exocytotic release of ATP, which we could not observe in the present work as it would undergo a quick catabolism into adenosine due to an increased expression of CD73 (Fig.…”

Section: Discussionmentioning

confidence: 97%

Contribution of adenosine and ATP to the carotid body chemosensory activity in ageing

Sacramento

Olea

Ribeiro

et al. 2019

The Journal of Physiology

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Key points Adenosine and ATP are excitatory neurotransmitters involved in the carotid body (CB) response to hypoxia. During ageing the CB exhibits a decline in its functionality, demonstrated by decreased hypoxic responses. In aged rats (20–24 months old) there is a decrease in: basal and hypoxic release of adenosine and ATP from the CB; expression of adenosine and ATP receptors in the petrosal ganglion; carotid sinus nerve (CSN) activity in response to hypoxia; and ventilatory responses to ischaemic hypoxia. There is also an increase in SNAP25, ENT1 and CD73 expression. It is concluded that, although CSN activity and ventilatory responses to hypoxia decrease with age, adjustments in purinergic metabolism in the CB in aged animals are present aiming to maintain the contribution of adenosine and ATP. The possible significance of the findings in the context of ageing and in CB‐associated pathologies is considered. Abstract During ageing the carotid body (CB) exhibits a decline in its functionality. Here we investigated the effect of ageing on functional CB characteristics as well as the contribution of adenosine and ATP to CB chemosensory activity. Experiments were performed in 3‐month‐old and 20‐ to 24‐month‐old male Wistar rats. Ageing decreased: the number of tyrosine hydroxylase immune‐positive cells, but not type II cells or nestin‐positive cells in the CB; the expression of P2X2 and A2A receptors in the petrosal ganglion; and the basal and hypoxic release of adenosine and ATP from the CB. Ageing increased ecto‐nucleotidase (CD73) immune‐positive cells and the expression of synaptosome associated protein 25 (SNAP25) and equilibrative nucleoside transporter 1 (ENT1) in the CB. Additionally, ageing did not modify basal carotid sinus nerve (CSN) activity or the activity in response to hypercapnia, but decreased CSN activity in hypoxia. The contribution of adenosine and ATP to stimuli‐evoked CSN chemosensory activity in aged animals followed the same pattern of 3‐month‐old animals. Bilateral common carotid occlusions during 5, 10 and 15 s increased ventilation proportionally to the duration of ischaemia, an effect decreased by ageing. ATP contributed around 50% to ischaemic‐ventilatory responses in young and aged rats; the contribution of adenosine was dependent on the intensity of ischaemia, being maximal in ischaemias of 5 s (50%) and much smaller in 15 s ischaemias. Our results demonstrate that both ATP and adenosine contribute to CB chemosensory activity in ageing. Though CB responses to hypoxia, but not to hypercapnia, decrease with age, the relative contribution of both ATP and adenosine for CB activity is maintained.

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Section: Discussionmentioning

confidence: 97%

Contribution of adenosine and ATP to the carotid body chemosensory activity in ageing

Sacramento

Olea

Ribeiro

et al. 2019

The Journal of Physiology

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“…In the brain, Nt5e can activate, rather than repress, microglia in a Parkinson’s disease model and contribute to neuronal toxicity 31 . Centenarian humans have lower Nt5e levels compared to octogenarians 56 , suggesting that a physiologic decrease is associated with normal, healthy aging.…”

Section: Discussionmentioning

confidence: 99%

Calorie restriction slows age-related microbiota changes in an Alzheimer’s disease model in female mice

Cox

Schafer

Sohn

et al. 2019

Sci Rep

102

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Alzheimer’s disease (AD) affects an estimated 5.8 million Americans, and advanced age is the greatest risk factor. AD patients have altered intestinal microbiota. Accordingly, depleting intestinal microbiota in AD animal models reduces amyloid-beta (Aβ) plaque deposition. Age-related changes in the microbiota contribute to immunologic and physiologic decline. Translationally relevant dietary manipulations may be an effective approach to slow microbiota changes during aging. We previously showed that calorie restriction (CR) reduced brain Aβ deposition in the well-established Tg2576 mouse model of AD. Presently, we investigated whether CR alters the microbiome during aging. We found that female Tg2576 mice have more substantial age-related microbiome changes compared to wildtype (WT) mice, including an increase in Bacteroides, which were normalized by CR. Specific gut microbiota changes were linked to Aβ levels, with greater effects in females than in males. In the gut, Tg2576 female mice had an enhanced intestinal inflammatory transcriptional profile, which was reversed by CR. Furthermore, we demonstrate that Bacteroides colonization exacerbates Aβ deposition, which may be a mechanism whereby the gut impacts AD pathogenesis. These results suggest that long-term CR may alter the gut environment and prevent the expansion of microbes that contribute to age-related cognitive decline.

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“…Hyperactivity of A 2A ARs in the aged brain is further reinforced by the parallel increase of the pathway responsible for the formation of the pool of adenosine selectively associated with the activation of A 2A ARs, namely ecto-5′-nucleotidase (CD73)-mediated formation of ATP-derived extracellular adenosine ( Augusto et al, 2013 ; Carmo et al, 2019 ; Gonçalves et al, 2019 ). In fact, different studies reported a robust increase of the activity of CD73 in the aged brain ( Fuchs, 1991 ; Cunha et al, 2001 ; Mackiewicz et al, 2006 ), as best heralded by the inverse association of CD73 activity with the probability of reaching centenarian ages ( Crooke et al, 2017 ). In parallel, the activity of AdoK is decreased in the aged brain ( Mackiewicz et al, 2006 ).…”

Section: Pharmacology – Novel Developmentsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update

et al. 2022

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Our previous International Union of Basic and Clinical Pharmacology report on the nomenclature and classification of adenosine receptors (2011) contained a number of emerging developments with respect to this G protein-coupled receptor subfamily, including protein structure, protein oligomerization, protein diversity, and allosteric modulation by small molecules. Since then, a wealth of new data and results has been added, allowing us to explore novel concepts such as target binding kinetics and biased signaling of adenosine receptors, to examine a multitude of receptor structures and novel ligands, to gauge new pharmacology, and to evaluate clinical trials with adenosine receptor ligands. This review should therefore be considered a further update of our previous reports from 2001 and 2011. Significance Statement Adenosine receptors (ARs) are of continuing interest for future treatment of chronic and acute disease conditions, including inflammatory diseases, neurodegenerative afflictions, and cancer. The design of AR agonists (“biased” or not) and antagonists is largely structure based now, thanks to the tremendous progress in AR structural biology. The A 2A - and A 2B AR appear to modulate the immune response in tumor biology. Many clinical trials for this indication are ongoing, whereas an A 2A AR antagonist (istradefylline) has been approved as an anti-Parkinson agent.

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Low expression of CD39 and CD73 genes in centenarians compared with octogenarians

Cited by 7 publications

References 28 publications

Contribution of adenosine and ATP to the carotid body chemosensory activity in ageing

Contribution of adenosine and ATP to the carotid body chemosensory activity in ageing

Calorie restriction slows age-related microbiota changes in an Alzheimer’s disease model in female mice

International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update

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