Longitudinal Muscle and Myocellular Changes in Community-Dwelling Men Over Two Decades of Successful Aging—The ULSAM Cohort Revisited

Skoglund, Elisabeth; Grönholdt‐Klein, Max; Rullman, Eric; Thornell, L.‐E.; Strömberg, Anna; Hedman, Anu; Cederholm, Tommy; Ulfhake, Brun; Gustafsson, Thomas

doi:10.1093/gerona/glz068

Cited by 9 publications

(14 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Primers were designed using the NCBI software (version June, 2008) Primer-BLAST (for nucleotide sequence and accession number, see Supplementary Materials ), and the gene transcripts analyzed here were selected based on earlier studies on aging rats [ 63 , 64 ], the response to axonal damage and regeneration in rats [ 65 ], and early- and advanced-aged muscles in humans [ 66 ]. Amplicons by qPCR were controlled with respect to length and the number of products with a melt curve, as well as agarose gel electrophoresis using ethidium bromide as a stain.…”

Section: Methodsmentioning

confidence: 99%

“…In this study, we used outbred rats to investigate the natural history of sarcopenia, with the aim of comparing the emergence and progression of motor behavioral deficits with the degree of muscle wasting and finding processes in the muscle that precede the clinical phase of this disease. To this end, we used a battery of tests to determine the onset and progression of motor behavioral deficits across the adult lifespan, changes in muscle mass and histology, and the qPCR of a panel of mRNA transcripts based on our previous findings in rats [ 63 , 64 , 65 ] and humans [ 66 ]. We selected the soleus component of the triceps surae muscle from male SD rats for study because it undergoes long work cycles in daily life and is important for postural mechanisms [ 67 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Emergence and Progression of Behavioral Motor Deficits and Skeletal Muscle Atrophy across the Adult Lifespan of the Rat

GrönholdtKlein,

Gorzi,

Wang

et al. 2023

Biology

Self Cite

View full text Add to dashboard Cite

The facultative loss of muscle mass and function during aging (sarcopenia) poses a serious threat to our independence and health. When activities of daily living are impaired (clinical phase), it appears that the processes leading to sarcopenia have been ongoing in humans for decades (preclinical phase). Here, we examined the natural history of sarcopenia in male outbred rats to compare the occurrence of motor behavioral deficits with the degree of muscle wasting and to explore the muscle-associated processes of the preclinical and clinical phases, respectively. Selected metrics were validated in female rats. We used the soleus muscle because of its long duty cycles and its importance in postural control. Results show that gait and coordination remain intact through middle age (40–60% of median lifespan) when muscle mass is largely preserved relative to body weight. However, the muscle shows numerous signs of remodeling with a shift in myofiber-type composition toward type I. As fiber-type prevalence shifted, fiber-type clustering also increased. The number of hybrid fibers, myofibers with central nuclei, and fibers expressing embryonic myosin increased from being barely detectable to a significant number (5–10%) at late middle age. In parallel, TGFβ1, Smad3, FBXO32, and MuRF1 mRNAs increased. In early (25-month-old) and advanced (30-month-old) aging, gait and coordination deteriorate with the progressive loss of muscle mass. In late middle age and early aging due to type II atrophy (>50%) followed by type I atrophy (>50%), the number of myofibers did not correlate with this process. In advanced age, atrophy is accompanied by a decrease in SCs and βCatenin mRNA, whereas several previously upregulated transcripts were downregulated. The re-expression of embryonic myosin in myofibers and the upregulation of mRNAs encoding the γ-subunit of the nicotinic acetylcholine receptor, the neuronal cell adhesion molecule, and myogenin that begins in late middle age suggest that one mechanism driving sarcopenia is the disruption of neuromuscular connectivity. We conclude that sarcopenia in rats, as in humans, has a long preclinical phase in which muscle undergoes extensive remodeling to maintain muscle mass and function. At later time points, these adaptive mechanisms fail, and sarcopenia becomes clinically manifest.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Emergence and Progression of Behavioral Motor Deficits and Skeletal Muscle Atrophy across the Adult Lifespan of the Rat

GrönholdtKlein,

Gorzi,

Wang

et al. 2023

Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the literature, the incidence, prevalence, and grading of severity as well as the clinical progression of the condition varies substantially, but studies are reasonably coherent on the evidence that primary sarcopenia becomes clinically assessable during the 5th-7th decades of life with a prevalence of >5%, with an annual progression of 0.5-2% per year (using above mass and strength criteria), and an accelerated progression beyond 70 years with a prevalence of >10%. Confounding factors, apart from differences in operational definitions and the relevance of the metrics used to define and grade sarcopenia, are problems associated with study design, either cross-sectional or longitudinal (Reid et al, 2014;Skoglund et al, 2020), and whether the studied populations are representative of the general population (Mitchell et al, 2012).…”

Section: Sarcopenia What Is Sarcopenia?mentioning

confidence: 99%

“…By using participants of the population-based Uppsala longitudinal study of adult men (ULSAM) cohort (Skoglund et al, 2020), changes in skeletal muscle expression in a set of candidate genes involved in muscle remodeling was analyzed longitudinally. At age 70, an activation of the pathways associated with UPS was observed but this response was significantly attenuated by age 88.…”

Section: Changes To the Remodeling Capacity Of Skeletal Muscles During Agingmentioning

confidence: 99%

Sarcopenia: What Is the Origin of This Aging-Induced Disorder?

Gustafsson

Ulfhake

2021

Front. Genet.

Self Cite

View full text Add to dashboard Cite

We here review the loss of muscle function and mass (sarcopenia) in the framework of human healthspan and lifespan, and mechanisms involved in aging. The rapidly changing composition of the human population will impact the incidence and the prevalence of aging-induced disorders such as sarcopenia and, henceforth, efforts to narrow the gap between healthspan and lifespan should have top priority. There are substantial knowledge gaps in our understanding of aging. Heritability is estimated to account for only 25% of lifespan length. However, as we push the expected lifespan at birth toward those that we consider long-lived, the genetics of aging may become increasingly important. Linkage studies of genetic polymorphisms to both the susceptibility and aggressiveness of sarcopenia are still missing. Such information is needed to shed light on the large variability in clinical outcomes between individuals and why some respond to interventions while others do not. We here make a case for the concept that sarcopenia has a neurogenic origin and that in manifest sarcopenia, nerve and myofibers enter into a vicious cycle that will escalate the disease progression. We point to gaps in knowledge, for example the crosstalk between the motor axon, terminal Schwann cell, and myofiber in the denervation processes that leads to a loss of motor units and muscle weakness. Further, we argue that the operational definition of sarcopenia should be complemented with dynamic metrics that, along with validated biomarkers, may facilitate early preclinical diagnosis of individuals vulnerable to develop advanced sarcopenia. We argue that preventive measures are likely to be more effective to counter act aging-induced disorders than efforts to treat manifest clinical conditions. To achieve compliance with a prescription of preventive measures that may be life-long, we need to identify reliable predictors to design rational and convincing interventions.

show abstract

“…For example, a strong upregulation of the acetylcholine receptors (AChR), normally confined to the NMJ, is evident along the length of the myofibre upon denervation (Merlie et al 1984). We (Karlsen et al 2019(Karlsen et al , 2020Soendenbroe et al 2019Soendenbroe et al , 2020 and others (Gigliotti et al 2015;Baehr et al 2016;Kelly et al 2018;Sonjak et al 2019;Daou et al 2020;Skoglund et al 2020;Lagerwaard et al 2021;Monti et al 2021) have availed ourselves of this to indirectly investigate myofibre innervation status in human muscle tissue.…”

Section: Introductionmentioning

confidence: 99%

Preserved stem cell content and innervation profile of elderly human skeletal muscle with lifelong recreational exercise

Soendenbroe

Dahl

Meulengracht

et al. 2022

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

Longitudinal Muscle and Myocellular Changes in Community-Dwelling Men Over Two Decades of Successful Aging—The ULSAM Cohort Revisited

Cited by 9 publications

References 47 publications

Emergence and Progression of Behavioral Motor Deficits and Skeletal Muscle Atrophy across the Adult Lifespan of the Rat

Emergence and Progression of Behavioral Motor Deficits and Skeletal Muscle Atrophy across the Adult Lifespan of the Rat

Sarcopenia: What Is the Origin of This Aging-Induced Disorder?

Preserved stem cell content and innervation profile of elderly human skeletal muscle with lifelong recreational exercise

Contact Info

Product

Resources

About