Older postmenopausal women with lower lean mass have hypermethylated sites in the PI3K-Akt pathway

Igor Massari Correia; Guilherme da Silva Rodrigues; Natália Yumi Noronha; Lígia Moriguchi Watanabe; Mariana Luciano de Almeida; Andressa Crystine da Silva Sobrinho; Carla Barbosa Nonino; Carlos Roberto Bueno Júnior

doi:10.3389/fphys.2023.1150821

Older postmenopausal women with lower lean mass have hypermethylated sites in the PI3K-Akt pathway

Front Physiol. 2023 Apr 10:14:1150821. doi: 10.3389/fphys.2023.1150821. eCollection 2023.

Authors

Igor Massari Correia¹, Guilherme da Silva Rodrigues², Natália Yumi Noronha², Lígia Moriguchi Watanabe³, Mariana Luciano de Almeida⁴, Andressa Crystine da Silva Sobrinho², Carla Barbosa Nonino⁴, Carlos Roberto Bueno Júnior^{1

2

4}

Affiliations

¹ School of Physical Education and Sport of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
² Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
³ Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
⁴ College of Nursing of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.

Abstract

Introduction: The decrease in lean mass is directly related to the loss of independence, muscle strength, and worse quality of life over the years. Although the genetic determinants of muscle mass were well recognized, recent literature has been uncovering new epigenetic factors affecting the state of muscular tissue. This study aimed to verify differences in the DNA methylation profile among Brazilian postmenopausal women aged 50-70 years according to the lean mass evaluation. Methods: A cross-sectional study comprised 40 women aged 50-70 years. After K-means cluster analysis the 40 participants were divided into two groups, the Lower Lean Mass group with 20 participants (61.1 ± 4.6 years) and the Higher Lean Mass group with 20 participants (60.7 ± 3.2 years). Lean mass was measured by dual-energy X-ray emission densitometry (DEXA). The participants' DNA was extracted using the Salting Out technique and subsequently, the Illumina 850k EPIC Infinium Methylation BeadChip was performed to obtain methylation data. Results: We obtained 1,913 differentially methylated sites (p ≤ 0.005 of β > 5% and β < -5%) in a total of 979 genes between groups (p ≤ 0.005; -5% > β > 5%). In addition, the PI3K-Akt pathway had the greatest power of significance with an FDR of 4.6 × 10^-3. Conclusion: Our results demonstrate a differentiation between specific sites of different genes, which have essential functions in body composition and energy metabolism, supporting future studies that aim to relate lean mass with epigenetics.

Keywords: DNA methylation; body composition; epigenetic; muscle loss; muscle strength.

Grants and funding

This work was supported in part by a grant from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (17/21361-2), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; 88882.180033/2018-01).