Evidence for sex-specific intramuscular changes associated to physical weakness in adults older than 75 years

Jelle C B C de Jong; Lars Verschuren; Martien P M Caspers; Marjanne D van der Hoek; Feike R van der Leij; Robert Kleemann; Anita M van den Hoek; Arie G Nieuwenhuizen; Jaap Keijer

doi:10.1186/s13293-023-00531-w

Evidence for sex-specific intramuscular changes associated to physical weakness in adults older than 75 years

Biol Sex Differ. 2023 Jul 10;14(1):45. doi: 10.1186/s13293-023-00531-w.

Authors

Affiliations

¹ Human and Animal Physiology, Wageningen University, P.O. Box 338, 6700AH, Wageningen, The Netherlands.
² Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands.
³ Department of Microbiology and Systems Biology, The Netherlands Organization for Applied Scientific Research (TNO), Zeist, The Netherlands.
⁴ Applied Research Centre Food and Dairy, Van Hall Larenstein University of Applied Sciences, Leeuwarden, The Netherlands.
⁵ MCL Academy, Medical Centre Leeuwarden, Leeuwarden, The Netherlands.
⁶ Research and Innovation Centre Agri, Food and Life Sciences, Inholland University of Applied Sciences, Delft and Amsterdam, The Netherlands.
⁷ Human and Animal Physiology, Wageningen University, P.O. Box 338, 6700AH, Wageningen, The Netherlands. Jaap.keijer@wur.nl.

Abstract

Background: Physical weakness is a key component of frailty, and is highly prevalent in older adults. While females have a higher prevalence and earlier onset, sex differences in the development of frailty-related physical weakness are hardly studied. Therefore, we investigated the intramuscular changes that differentiate between fit and weak older adults for each sex separately.

Methods: Male (n = 28) and female (n = 26) older adults (75 + years) were grouped on the basis of their ranks according to three frailty-related physical performance criteria. Muscle biopsies taken from vastus lateralis muscle were used for transcriptome and histological examination. Pairwise comparisons were made between the fittest and weakest groups for each sex separately, and potential sex-specific effects were assessed.

Results: Weak females were characterized by a higher expression of inflammatory pathways and infiltration of NOX2-expressing immune cells, concomitant with a higher VCAM1 expression. Weak males were characterized by a smaller diameter of type 2 (fast) myofibers and lower expression of PRKN. In addition, weakness-associated transcriptome changes in the muscle were distinct from aging, suggesting that the pathophysiology of frailty-associated physical weakness does not necessarily depend on aging.

Conclusions: We conclude that physical weakness-associated changes in muscle are sex-specific and recommend that sex differences are taken into account in research on frailty, as these differences may have a large impact on the development of (pharmaceutical) interventions against frailty.

Trial registration number: The FITAAL study was registered in the Dutch Trial Register, with registration code NTR6124 on 14-11-2016 ( https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6124 ).

Highlights: • In female, but not male older adults, physical weakness was associated with a higher expression of intramuscular markers for inflammation. • In male, but not female older adults, physical weakness was associated with a smaller diameter of type 2 (fast) myofibers and lower PRKN expression. • Fit older adults (of both sexes) maintained expression levels comparable to young participants of weakness related genes, differing from frail participants.

Keywords: Frailty; Gender; Inflammation; Muscle-aging; Myofiber type; Older adults.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aging
Ethnicity
Female
Frailty*
Humans
Inflammation
Male
Sex Characteristics

Associated data

NTR/NTR6124