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ADNP differentially interact with genes/proteins in correlation with aging: a novel marker for muscle aging

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Abstract

Activity-dependent neuroprotective protein (ADNP) is essential for embryonic development with ADNP mutations leading to syndromic autism, coupled with intellectual disabilities and motor developmental delays. Here, mining human muscle gene-expression databases, we have investigated the association of ADNP transcripts with muscle aging. We discovered increased ADNP and its paralogue ADNP2 expression in the vastus lateralis muscle of aged compared to young subjects, as well as altered expression of the ADNP and the ADNP2 genes in bicep brachii muscle of elderly people, in a sex-dependent manner. Prolonged exercise resulted in decreased ADNP expression, and increased ADNP2 expression in an age-dependent manner in the vastus lateralis muscle. ADNP expression level was further correlated with 49 genes showing age-dependent changes in muscle transcript expression. A high degree of correlation with ADNP was discovered for 24 genes with the leading gene/protein being NMNAT1 (nicotinamide nucleotide adenylyl transferase 1). Looking at correlations differentiating the young and the old muscles and comparing protein interactions revealed an association of ADNP with the cell division cycle 5-like protein (CDC5L), and an aging-muscle–related interactive pathway in the vastus lateralis. In the bicep brachii, very high correlation was detected with genes associated with immune functions as well as mitochondrial structure and function among others. Taken together, the results suggest a direct association of ADNP with muscle strength and implicate ADNP fortification in the protection against age-associated muscle wasting.

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Acknowledgments

This study is in partial fulfillment of the PhD study requirements of Oxana Kapitansky. We thank Noy Amram, Adva Hadar, Irena Voinsky, Chen Slominsky-Lustgarten, Yael Toren, Koral Goltseker, and Liora Rotero-Rosenberg for technical and editorial valuable help.

Funding

Research was supported by funds from the Israel Science Foundation (ISF) grant (1424/14), ERA-NET neuron AUTISYN, AMN Foundation, Drs. Ronith and Armand Stemmer, and Mr. Arthur Gerbi (French Friends of Tel Aviv University), as well as Canadian (Mrs. Anne and Mr. Alex Cohen) and Spanish Friends of Tel Aviv University, Alicia Koplowitz Foundation.

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  1. The Lily and Avraham Gildor Chair for the Investigation of Growth Factors; The Elton Laboratory for Neuroendocrinology; Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Sagol School of Neuroscience and Adams Super Center for Brain Studies, Tel Aviv University, 69978, Tel Aviv, Israel

    Oxana Kapitansky & Illana Gozes

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  1. Oxana Kapitansky
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Correspondence to Illana Gozes.

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Professor Illana Gozes in the Chief Scientific Officer of Coronis Neurosciences, developing CP201 (under patent protection and license from Ramot at Tel Aviv University).

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Kapitansky, O., Gozes, I. ADNP differentially interact with genes/proteins in correlation with aging: a novel marker for muscle aging. GeroScience 41, 321–340 (2019). https://doi.org/10.1007/s11357-019-00079-x

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