International Journal of

Molecular Sciences

Editorial
Musculoskeletal Aging and Sarcopenia in the Elderly
Emanuele Marzetti 1,2

1 Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, 00168 Rome, Italy;

emanuele.marzetti@policlinicogemelli.it; Tel.: +39-(06)-3015-5559
2 Department of Geriatrics and Orthopedics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy

The loss of skeletal muscle mass and strength/function, referred to as sarcopenia, is a

pervasive feature of aging [1]. The remarkable prevalence of sarcopenia and its association
with a broad range of negative health-related outcomes have instigated a great deal of
research on the pathophysiology of muscle aging. This has led to the identification of several
biological pathways that may be exploited for biomarker discovery and/or therapeutic
purposes. This Special Issue convened basic and clinical researchers working in the areas
of sarcopenia and muscle physiology to foster our understanding of the molecular events
associated with muscle aging and their modulation by specific interventions.
Omics platforms are especially well-suited for unveiling complex molecular patterns that
might be dissected to discover specific biological pathways. The study by Zampino et al. [2]
is a notable example of the application of such an approach to the study of muscle aging.
Through the measurement of the plasma concentration of a large protein array, the authors
identified a proteomic signature of muscle mitochondrial function assayed by phosphorous
magnetic resonance spectroscopy [2]. The relevance of mitochondrial dysfunction to
sarcopenia is further highlighted by the observation that alterations in intracellular calcium
handling impact mitochondrial bioenergetics [3]. Muscle fiber denervation, an event
involved in the pathogenesis of sarcopenia, induces damage of membrane structures



involved in calcium handling and excitation–contraction coupling, and disruption of the


mitochondrial network [3]. These alterations were also described in physically inactive old
Citation: Marzetti, E. mice and were rescued by electrical stimulation regular exercise in both rodents and older
Musculoskeletal Aging and
persons [3].
Sarcopenia in the Elderly. Int. J. Mol.
The maintenance of a functional mitochondrial network in skeletal myofibers re-
Sci. 2022, 23, 2808. https://doi.org/
lies on the fine regulation of a set of mitochondrial quality control (MQC) pathways,
10.3390/ijms23052808
involving mitochondrial proteostasis, dynamics, biogenesis, and mitochondrial autophagy
Received: 24 February 2022 (mitophagy) [4]. The efficiency of MQC declines with advancing age in various tissues,
Accepted: 1 March 2022 including muscle, which is considered to be a major factor in the development of sar-
Published: 4 March 2022 copenia [5]. Indeed, alterations in mitochondrial dynamics and declining mitochondrial
Publisher’s Note: MDPI stays neutral
turnover cause an accumulation of dysfunctional organelles within skeletal myofibers,
with regard to jurisdictional claims in leading to impaired bioenergetics and activation of catabolic pathways [6]. It is noteworthy
published maps and institutional affil- that the impact of myocyte mitochondrial dysfunction is not limited to the muscle, but can
iations. extend to distant organs (e.g., liver, heart, pancreas, white adipose tissue) and affect whole-
body metabolic homeostasis through the release into the bloodstream of myomitokines,
chiefly fibroblast growth factor 21 and growth and differentiation factor 15 [6].
Similar to defective autophagy, an overactivation of this degradative pathway, for
Copyright: © 2022 by the author. instance during starvation, leads to muscle tissue depletion [7]. Malnutrition is frequently
Licensee MDPI, Basel, Switzerland. observed in patients with congestive heart failure (CHF) and contributes to hyperactivation
This article is an open access article of autophagy in cardiac and skeletal myocytes, which is thought to play a prominent
distributed under the terms and role in the progression of heart dysfunction and muscle atrophy [8]. Indeed, sarcopenia
conditions of the Creative Commons
is highly prevalent in older adults with CHF [9] and independently predicts poor prog-
Attribution (CC BY) license (https://
nosis [10]. Supplementation with essential amino acids may promote heart and skeletal
creativecommons.org/licenses/by/
muscle anabolism and improve survival in patients with CHF, at least partly through
4.0/).

Int. J. Mol. Sci. 2022, 23, 2808. https://doi.org/10.3390/ijms23052808 https://www.mdpi.com/journal/ijms

Int. J. Mol. Sci. 2022, 23, 2808 2 of 3

favoring mitochondrial biogenesis and attenuating the overactivation of autophagy [11].

Hence, the nutritional status should be carefully monitored in patients with CHF, and
essential amino acid supplementation should be considered to mitigate cardiac dysfunction
and muscle atrophy resulting from a maladaptive overactivation of autophagy [8].
Taurine, a non-essential amino acid abundant in nuts, shellfish, eggs, meat, and dairy
products, is another promising nutrient that might be supplemented to promote muscle
health and counteract sarcopenia [12]. The administration of taurine to myogenic L6 cells
was shown to stimulate cell differentiation by downregulating the expression inflammatory
molecules and through modulating autophagy and apoptosis [12].
Together with optimal nutrition, physical activity and exercise are the most effective
interventions to prevent and treat sarcopenia [13]. Physical exercise, besides promoting
muscle hypertrophy and strength gain, is well-known for its beneficial effects on the
cardiovascular system and whole-body metabolism [14]. These effects are conveyed, at
least partly, through the release of myokines, such as decorin, insulin-like growth factor 1,
myonectin, apelin, musclin, and interleukin 6 [15]. Interestingly, time-scheduled physical
exercise has been shown to restore the circadian rhythm in the skeletal muscle [16], which
is altered during aging and in people with shift work or sleep disorders. Disruption of the
circadian rhythm has been associated with detrimental changes in body composition and
increased risk of sarcopenia [17,18]. The mechanisms by which circadian rhythm disruption
impacts muscle health are not fully elucidated. However, studies in mice lacking CLOCK
and BMAL1 have shown that clock gene deficiency causes mitochondrial dysfunction
and muscle degeneration [19]. Hence, the restoration of the circadian rhythm through
time-scheduled exercise might amplify the beneficial effects of exercise on muscle in older
adults with sarcopenia [20]. This possibility warrants further investigation.

Funding: This work was supported by an intramural grant by the Università Cattolica del Sacro
Cuore [D1.2020].
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: No data were generated for the present article.
Conflicts of Interest: The author declares no conflict of interest.

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