Myofibers (Skeletal Muscle Fibers)

Skeletal muscle fibers — myofibers — are the terminally-differentiated, post-mitotic, multinucleated contractile cells that constitute the bulk of skeletal muscle mass. They are formed embryonically and postnatally by the fusion of proliferating myoblasts into syncytia containing hundreds to thousands of peripherally-positioned myonuclei within a shared cytoplasm (sarcoplasm). Because myofibers cannot divide, repair of damaged fibers depends entirely on the resident stem cell population, satellite-cells, which fuse with existing fibers or with each other to form new myotubes. In aging, myofibers are the primary structural substrate of sarcopenia: they atrophy, lose mitochondrial competence, accumulate proteolytic damage, and are progressively denervated — collectively driving the decline in muscle mass, strength, and power that characterizes normal human aging.

This page is the canonical atomic home for myofiber biology. Tissue-level organization, satellite cell biology, and intervention evidence tables are on skeletal-muscle; the sarcopenic phenotype is on sarcopenia.

Identity and structure

Myofibers are multinucleated syncytia (each fiber may contain hundreds of myonuclei in long fibers), enveloped by the sarcolemma (plasma membrane) and an outer basal lamina. The sarcoplasm is packed with parallel myofibrils organized into sarcomeres — repeating contractile units delineated by Z-discs, consisting of interdigitated thick filaments (myosin) and thin filaments (actin, troponin, tropomyosin). Key structural proteins:

Protein	Gene	Role
Myosin heavy chain (MyHC)	MYH7 / MYH2 / MYH1 / MYH4	Principal force generator; isoform determines fiber type
Desmin	DES	Intermediate filament; links Z-discs laterally and to sarcolemma
Dystrophin	DMD	Connects cytoskeleton to extracellular matrix via DGC; structural integrity
Alpha-actinin (sarcomeric)	ACTN2 / ACTN3	Z-disc cross-linker; anchors thin filaments
Titin	TTN	Elastic protein spanning Z-disc to M-line; myosin scaffold

Myofibers are post-mitotic: they do not undergo mitotic division. Myonuclei are long-lived and can exchange mRNA across the syncytium via the myoplasmic reticulum, allowing regional specification of gene expression along fiber length (e.g., differences in NMJ-adjacent vs. central myonuclear domains).

Fiber types and human myosin-heavy-chain isoform mapping

Human skeletal muscle contains three principal MyHC isoforms in adult limb muscles, encoding distinct contractile and metabolic phenotypes ¹:

Fiber type	MyHC isoform	Gene	Metabolic profile	Fatigue resistance	Force / power
Type I (slow-twitch)	MyHC-I (slow)	MYH7	Oxidative; high mitochondrial density; high myoglobin	High	Low–moderate
Type IIa (fast oxidative)	MyHC-IIa	MYH2	Oxidative-glycolytic; intermediate	Moderate	Moderate–high
Type IIx (fast glycolytic)	MyHC-IIx	MYH1	Glycolytic; low mitochondrial density	Low	High
Type IIb (very fast)	MyHC-IIb	MYH4	Pure glycolytic	Very low	Very high

Key human-specific note: Type IIb fibers (MYH4) are essentially absent in adult human limb muscles under normal physiological conditions, in contrast to rodents (where MYH4 predominates in fast hindlimb muscles). The “2B” fibers described in older human histochemical literature likely correspond to 2X fibers at the protein level; adult human limb muscle contains no more than trace MYH4 protein. The primary fast-fiber type in adult human muscle is Type IIa/IIx (MYH2/MYH1). gap/needs-replication — the cited Oldfors 2004 reference is primarily a myopathy paper, not a dedicated fiber-type atlas; the MYH4/2B absence in humans is widely accepted in myology literature but the primary citation here is indirect. A Schiaffino & Reggiani review or a dedicated human proteomics study (e.g. Murgia et al. single-fiber proteomics) would be the preferred canonical reference.

In practice, many human fibers co-express two MyHC isoforms (I+IIa, IIa+IIx) — these “hybrid” fibers are more prevalent in muscle undergoing remodeling (training, detraining, aging) and represent transitional states along the fiber-type continuum.

Aging biology

Preferential Type II fiber atrophy

The most consistent and best-documented myofiber change with human aging is preferential atrophy of Type II (fast-twitch) fibers. Nilwik et al. (2013), in a cross-sectional biopsy study of 25 young (23±1 yr) and 26 elderly (71±1 yr) men, found that Type II fiber cross-sectional area (CSA) was 29% smaller in elderly men (P<0.001), and that this difference in Type II fiber size fully explained the reduction in quadriceps CSA between age groups (68±2 vs 80±2 cm²) ². Type I fiber size showed a non-significant trend toward smaller size in the elderly (P=0.052). After 6 months of resistance training, elderly participants increased Type II fiber CSA by 24±8% (P<0.01), accounting for the entire increase in quadriceps muscle CSA — establishing Type II fiber atrophy as the primary structural correlate of sarcopenic muscle loss.

This pattern is mechanistically linked to the preferential denervation of fast motor neurons with aging (see Neuromuscular junction section below), as well as to the inherent vulnerability of fast, glycolytic fibers to proteolytic pathways activated under anabolic insufficiency.

Dimension	Status
Pathway conserved in humans?	yes
Phenotype conserved in humans?	yes (cross-sectional biopsy and imaging data; Nilwik 2013 and others)
Replicated in humans?	yes (multiple cross-sectional studies; longitudinal data more limited)

Ubiquitin-proteasome system (UPS) / atrogene axis

The primary molecular executor of myofiber protein degradation in aging and atrophy is the ubiquitin-proteasome system (UPS), regulated via the atrogene axis. Under anabolic insufficiency (reduced insulin-like growth factor 1 / IGF-1 signaling, reduced amino acid supply, or elevated inflammatory cytokines), the phosphoinositide 3-kinase (PI3K) / AKT kinase pathway is insufficiently activated, permitting nuclear translocation of FOXO transcription factors (primarily FOXO1 and FOXO3a).

FOXO3a directly binds the promoter of atrogin-1 (also called MAFbx; gene: FBXO32) and drives its transcription, inducing myofiber atrophy ³. Bodine et al. (2001) identified both atrogin-1 (MAFbx/FBXO32) and MuRF1 (Muscle RING Finger 1; gene: TRIM63) as muscle-specific E3 ubiquitin ligases whose expression is strongly upregulated across multiple atrophy models — transcript profiling in rat across denervation, immobilization, and hindlimb suspension, plus dexamethasone and IL-1 treatment — with mouse KO experiments demonstrating that MAFbx−/− mice showed ~56% and MuRF1−/− mice ~36% sparing of muscle mass after 14-day denervation vs wild-type ⁴. MuRF1 targets structural myofibrillar proteins including myosin heavy chain isoforms for ubiquitin-mediated proteasomal degradation, directly reducing sarcomere protein content.

In aging human muscle, atrogin-1 and MuRF1 expression increases with age and correlates with reduced muscle mass ⁵. The upstream driver is the intersection of reduced IGF-1/AKT signaling (anabolic resistance — see below) and elevated pro-inflammatory cytokines. gap/unsourced — the precise fold-induction of atrogin-1 and MuRF1 in biopsy samples from aged vs. young humans across multiple studies needs quantitative reconciliation against primary sources; see skeletal-muscle § Limitations and gaps.

Inflammatory signals independently activate this axis: tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) from senescent cells (cellular-senescence SASP) and from systemic inflammaging activate nuclear factor kappa B (NF-κB) → suppress AKT → derepress FOXO → induce atrogin-1/MuRF1, creating a direct cytokine-to-catabolism pathway in myofibers. gap/unsourced — NF-κB → FOXO → atrogin induction in aged human muscle specifically needs primary citation separate from acute inflammation models.

Anabolic resistance and mTORC1 blunting

Aged myofibers display anabolic resistance: the mTORC1 signaling response per unit amino acid stimulus is blunted relative to young muscle ⁶. The threshold amount of leucine required to maximally stimulate muscle protein synthesis (MPS) is higher in older adults than in young adults. Practical consequence: the protein recommended dietary allowance (RDA) of 0.8 g/kg/day is insufficient to maintain positive protein balance in older adults; current consensus ranges from 1.0–1.6 g/kg/day depending on activity level, with leucine content per meal (≥2.5–3 g) being the key mTORC1 trigger.

The molecular basis is an upstream defect in the AKT → TSC1/2 → RHEB → mTORC1 cascade combined with reduced mTORC1 lysosomal recruitment via the Ragulator complex, likely secondary to both reduced IGF-1 and altered amino acid transporter expression. This is distinct from the FOXO axis above — the two represent the parallel “suppress anabolism” and “activate catabolism” arms of myofiber proteostasis collapse in aging.

Full pathway detail: mtor and insulin-igf1.

Mitochondrial decline and COX-deficient ragged-red fibers

Aged myofibers accumulate mitochondrial DNA (mtDNA) deletions that expand clonally within individual fiber segments over decades, creating mosaic patches of segments with severely impaired respiratory chain activity. Histochemically, these appear as cytochrome c oxidase (COX)-deficient segments in modified Gomori trichrome staining — the classic “ragged-red fibers” (RRF) appearance reflecting mitochondrial proliferation in response to bioenergetic failure.

Kimoloi et al. (2022) demonstrated in a mouse model that mtDNA alterations in myofibers alone are insufficient to cause sarcopenia without concomitant effects on muscle stem cells — the COX-deficient fibers activate compensatory regeneration that, if the stem cell pool carries mtDNA deletions, leads to progressive fiber atrophy ⁷. Type IIB fibers show preferential vulnerability to mtDNA-deletion-induced respiratory chain defects ⁸, consistent with their higher aerobic demand per unit mitochondrial density and their preferential atrophy in aging.

Overall mitochondrial content, cristae density, and maximal oxidative phosphorylation capacity decline in aged human skeletal muscle, paralleling the mitochondrial-dysfunction hallmark. Impaired mitophagy (see next section) prevents clearance of dysfunctional mitochondria.

Dimension	Status
Pathway (mtDNA deletion accumulation) conserved in humans?	yes
COX-deficient fiber patches in aged human muscle?	yes (histopathologically documented in multiple studies)
Causal link to sarcopenia via stem cell interaction?	partial — mechanistic model in mice; human longitudinal causal data limited

Autophagy and mitophagy dysregulation

Constitutive autophagy is essential for myofiber homeostasis. Masiero et al. (2009) showed that muscle-specific conditional deletion of Atg7 (the E1-like enzyme required for autophagosome formation) in mice — using a myosin light chain 1 fast (MLC1f) promoter-driven Cre — caused profound muscle atrophy (~40% CSA reduction), age-dependent loss of specific force, accumulation of abnormal mitochondria, distended sarcoplasmic reticulum, and disorganized sarcomeres ⁹. This established that autophagy flux is not merely a stress response in muscle but is continuously required to clear dysfunctional organelles and protein aggregates.

In aging myofibers, autophagy is dysregulated in a context-dependent manner:

Insufficient basal autophagy flux — allows damaged mitochondria, oxidized proteins, and aggregated sarcomeric proteins to accumulate, driving the disabled-macroautophagy hallmark.
Impaired selective mitophagy — dysfunctional mitochondria evade PINK1/Parkin-mediated mitophagy labeling; their persistence amplifies reactive oxygen species (ROS) production and contributes to the COX-deficient fiber phenotype.

Dimension	Status
Atg7 KO myopathy pathway conserved in humans?	partial (ATG7 LOF mutations → myopathy in humans; mechanism presumed conserved)
Impaired autophagy flux in aged human muscle?	partial — indirect biomarker evidence; direct flux measurements limited
Replicated in humans?	no (Atg7 cKO is a mouse model) gap/needs-human-replication

Neuromuscular junction denervation

Age-related loss of motor neurons and fragmentation of the neuromuscular junction (NMJ) is a major, often underappreciated, driver of myofiber atrophy. By approximately age 70, healthy older adults show approximately 40% fewer functional motor units compared to young adults, with surviving motor units increasing in size (~50%) and complexity through collateral reinnervation of orphaned fibers ¹⁰. Individual Type II fibers are preferentially denervated — consistent with the preferential loss of fast motor neurons with aging ¹¹. Chronically denervated fibers undergo neurogenic atrophy via both UPS/atrogene activation and impaired anabolic signaling.

The prostaglandin-degrading gerozyme 15-pgdh (gene: HPGD) rises in aged muscle and rises further after denervation, depleting local prostaglandin E2 (PGE2). Pharmacological inhibition of 15-PGDH with sw033291 restored NMJ density, motor-axon regeneration, and contractile force in both acute crush-injury and chronically-denervated aged mice, with 15-PGDH aggregates marking “target fibers” in human neurogenic myopathies ¹². This positions 15-PGDH as a gerozyme acting across both myofiber atrophy (via PGE2-EP4 → ↑mitochondrial biogenesis, ↑autophagy flux, ↓TGF-β, ↓UPS; see palla-2021-15pgdh-muscle-rejuvenation) and the pre-synaptic NMJ. Not yet in clinical trials as of 2026-06-15. gap/needs-human-replication

Full denervation mechanism and molecular detail: skeletal-muscle § Neuromuscular junction degeneration; see also bakooshli-2023-15pgdh-nmj-regeneration and palla-2021-15pgdh-muscle-rejuvenation.

Hallmark connections

Hallmark	Myofiber mechanism
loss-of-proteostasis	Atrogin-1/MuRF1 UPS axis degrades myosin; protein aggregates accumulate; sarcomere disorganization
mitochondrial-dysfunction	mtDNA deletions → COX-deficient fiber segments; impaired mitophagy; reduced oxidative capacity
disabled-macroautophagy	Atg7 KO phenotype: atrophy + organelle accumulation; impaired autophagy flux with age
deregulated-nutrient-sensing	Anabolic resistance: blunted mTORC1 per amino acid stimulus; IGF-1/AKT pathway insufficiency
chronic-inflammation	Inflammaging cytokines (IL-6, TNF-α) activate NF-κB → suppress AKT → derepress FOXO → induce atrogin-1/MuRF1
altered-intercellular-communication	Denervation (motor neuron-myofiber signaling disrupted); systemic milieu drives anabolic resistance; 15-PGDH/PGE2 axis

Aging-protective interventions (summary)

Full ranked evidence table is on skeletal-muscle; listed here for navigational completeness with myofiber-specific mechanism:

Resistance training — activates mTORC1, stimulates myofibrillar protein synthesis, induces Type II fiber hypertrophy specifically; reverses atrogin-1/MuRF1 induction; most evidence-supported intervention.
Adequate protein intake (≥1.2 g/kg/day in older adults; leucine-rich sources preferred) — overcomes anabolic resistance threshold; whey protein and leucine supplementation transiently restore mTORC1 response.
15-PGDH inhibition (preclinical; sw033291) — restores PGE2-EP4 → mitochondrial biogenesis + autophagy + reduced UPS; also restores NMJ. Preclinical only; cancer-aging tradeoff caveat (15-PGDH is a colon tumor suppressor; see cancer-aging-tradeoffs). gap/needs-human-replication
Senolytics (fisetin, dasatinib + quercetin) — remove p16+ senescent satellite cells and SASP producers from the myofiber niche, reducing inflammaging-driven catabolism. The hypertrophic/regenerative stimulus itself induces senescent cells (~2 wk after a resistance bout in humans); aged muscle over-accumulates them and has blunted hypertrophy, which a hit-and-run D+Q course rescued in old mice ¹³¹⁴. Benefit is age-specific; senolytic rescue is mouse-only. Preclinical for sarcopenia endpoint; no human senolytic + resistance-training trial. gap/needs-human-replication

Limitations and gaps

#gap/unsourced — quantitative fold-induction of atrogin-1 (FBXO32) and MuRF1 (TRIM63) in aged human muscle biopsies vs. young; see skeletal-muscle § Limitations and gaps for parent tracking of this gap.
#gap/unsourced — NF-κB → FOXO → atrogin induction cascade in aged (vs. acutely inflamed) human muscle: mechanism is extrapolated from in vitro cytokine treatment models; aged human muscle primary citation needed.
#gap/needs-replication — MYH4/Type IIb fiber absence in adult human limb muscle: the cited Oldfors 2004 reference is a myopathy paper, not a dedicated fiber-type atlas; recommend replacing or supplementing with a Schiaffino & Reggiani review or Murgia et al. single-fiber proteomics study as the canonical human isoform citation.
#gap/needs-human-replication — Atg7 muscle-conditional KO myopathy (Masiero 2009; MLC1f-Cre;Atg7^flox/flox mice) is mouse evidence; human ATG7 loss-of-function mutations do cause myopathy but the aging-context flux-suppression claim is not directly established in aged human biopsies.
#gap/needs-human-replication — 15-PGDH / SW033291 / NMJ restoration: all preclinical mouse evidence; no registered human trial as of 2026-06-15.
#gap/needs-human-replication — Senolytics clearing SASP from myofiber niche: no sarcopenia-specific human trial.
#gap/needs-singlecell-data — Single-nucleus RNA-seq aging signature of myofibers not integrated (snRNA-seq required for post-mitotic multinucleated cells; Tabula Muris Senis has limited myofiber snRNA data).
#gap/contradictory-evidence — Autophagy paradox: insufficient basal autophagy causes myopathy (Masiero 2009), yet excessive autophagy flux is also observed in some wasting conditions; the net aging direction in any given muscle bed is context-dependent.
#gap/long-term-unknown — Long-term consequences of 15-PGDH inhibition on colon cancer risk not characterized in aging-specific therapeutic context.

Footnotes

PMID 15605950 (no valid CrossRef DOI registered for Acta Myologica 2004 issues) · Oldfors A, Tajsharghi H, Darin N, Lindberg C · “Myopathies associated with myosin heavy chain mutations” · Acta Myologica 2004;23(2):90-96 · review of mutation-associated myopathies · model: human · Contains canonical MYH isoform assignments: Type I fibres = MYH7; type 2A fibres = MYH2; type 2B fibres (histochemical) = MYH1 (IIx at the protein level); MYH4 (true IIb) minimal to absent in adult human limb muscle · Note: this paper’s primary focus is congenital myopathies from MYH mutations, not a normal fiber-type atlas; the isoform table is incidental to the main thesis. For the canonical adult human fiber-type isoform table, also see Schiaffino & Reggiani reviews. · gap/no-fulltext-access — closed-access; metadata and abstract confirmed via PubMed efetch; original DOI string in wiki was invalid (404) ↩
doi:10.1016/j.exger.2013.02.012 · Nilwik R, Snijders T, Leenders M, Groen BB, van Kranenburg J, Verdijk LB, van Loon LJ · Experimental Gerontology 2013;48(5):492-498 · PMID 23425621 · cross-sectional biopsy study · n=25 young (23±1 yr) + 26 elderly (71±1 yr) men · Type II fiber CSA 29% smaller in elderly (P<0.001); Type I fiber showed a non-significant trend toward smaller size (P=0.052); Type II fiber atrophy fully explained the reduction in quadriceps CSA (68±2 vs 80±2 cm²); 6-month resistance training increased Type II fiber CSA by 24±8% (P<0.01), accounting for 100±3% of the increase in quadriceps CSA · model: human · closed-access, abstract verified via PubMed gap/no-fulltext-access · citation_percentile 100 (721 citations) ↩
doi:10.1016/s0092-8674(04)00400-3 · Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, Walsh K, Schiaffino S, Lecker SH, Goldberg AL · Cell 2004;117(3):399-412 · PMID 15109499 · in-vivo + in-vitro · model: mouse (C57BL/6) + C2C12 myotubes · FOXO3a directly binds atrogin-1 promoter and induces transcription; IGF-1/AKT activation inhibits FOXO and atrogin-1; blocking FOXO activation prevents starvation-induced atrogin-1 induction and glucocorticoid-induced atrophy · citation_percentile 100 (2905 citations) ↩
doi:10.1126/science.1065874 · Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA et al. · Science 2001;294(5547):1704-1708 · PMID 11679633 · in-vivo · model: rat (Sprague Dawley; transcript profiling in 3 atrophy models: denervation, immobilization, hindlimb suspension) + mouse KO validation · transcript profiling identified MAFbx (atrogin-1/FBXO32) and MuRF1 (TRIM63) as the 2 genes upregulated across all atrophy conditions; also upregulated by dexamethasone and IL-1; MAFbx−/− mice showed 56% muscle mass sparing at 14d denervation vs WT; MuRF1−/− showed 36% sparing at 14d; n=5–10 mice/group · citation_percentile 100 (3428 citations) ↩
doi:10.1152/ajpendo.00204.2014 · Bodine SC, Baehr LM · American Journal of Physiology - Endocrinology and Metabolism 2014 · PMID 25096180 · review · atrogin-1/FBXO32 and MuRF1/TRIM63 are established markers and mediators of muscle atrophy across multiple conditions including aging; review of substrate specificity and regulatory evidence ↩
doi:10.3945/jn.116.234518 · De Bandt JP · Journal of Nutrition 2016 · PMID 27934653 · review · anabolic resistance in aged muscle: decreased sensitivity and responsiveness of muscle protein synthesis to amino acids; leucine supplementation partially mitigates via mTORC1 activation; aged muscle shows reduced mTORC1 signaling per unit leucine stimulus ↩
doi:10.1002/jcsm.13026 · Kimoloi S, Sen A, Guenther S, Braun T, Brügmann T, Sasse P, Wiesner RJ, Pla-Martín D, Baris OR · Journal of Cachexia, Sarcopenia and Muscle 2022;13(4):2132-2145 · PMID 35765148 · in-vivo · model: mouse (K320E^skm — mtDNA instability in myofibers; K320E^msc — in muscle stem cells) · mtDNA deletions in myofibers alone caused COX-deficient fiber patches (up to 17% in gastrocnemius) but preserved muscle mass; stem cell mtDNA alterations caused impaired regeneration and sarcopenia; combined data support a two-hit model gap/needs-human-replication ↩
doi:10.1167/iovs.61.12.14 · Oexner RR, Pla-Martín D, Paß T et al. · Investigative Ophthalmology & Visual Science 2020;61(12):14 · PMID 33057669 · in-vivo · model: mouse · Type IIB fibers show selective vulnerability to mtDNA deletion-induced respiratory chain defects; COX-deficiency increased from 1.04% at 12 mo to 7.01% at 24 mo · gap/needs-human-replication — mouse extraocular muscle model; fiber-type selectivity in human limb aging muscle not directly established here ↩
doi:10.1016/j.cmet.2009.10.008 · Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, Metzger D, Reggiani C, Schiaffino S, Sandri M · Cell Metabolism 2009;10(6):507-515 · PMID 19945408 · in-vivo · model: mouse — muscle-specific Atg7 conditional KO (MLC1f-Cre;Atg7^flox/flox; myosin light chain 1 fast promoter drives Cre) · Atg7 deletion → profound muscle atrophy (~40% CSA reduction in both sexes), age-dependent decrease in specific force, accumulation of abnormal mitochondria, distended sarcoplasmic reticulum, disorganized sarcomeres; atrogin-1 and MuRF1 transcriptionally upregulated; autophagy inhibition exacerbated muscle loss under denervation and fasting · highly cited (~1242 citations) ↩
doi:10.1007/s10522-015-9627-3 · Piasecki M, Ireland A, Jones DA, McPhee JS · Biogerontology 2016;17(3):485-496 · PMID 26667009 · review · model: human (electromyographic motor unit counting studies) · approximately 40% fewer motor units by age ~71 vs young adults; surviving motor units enlarge ~50% via collateral reinnervation; NMJ transmission stability decreases with age · OA (hybrid) · citation_percentile 100 (159 citations) ↩
doi:10.4081/ejtm.2022.10416 · Coletti C, Acosta GF, Keslacy S, Coletti D · European Journal of Translational Myology 2022;32(1):10416 · PMID 35234025 · review · Type II fast fibers preferentially undergo denervation and are reinnervated by slow motor neurons; exercise promotes reinnervation in aging ↩
bakooshli-2023-15pgdh-nmj-regeneration · doi:10.1126/scitranslmed.adg1485 · PMID 37820010 · PMC10763629 · Bakooshli MA et al., Blau HM lab · Science Translational Medicine 2023;15(717):eadg1485 · in-vivo (sciatic crush + chronic denervation + aged mouse) + human IHC · 15-PGDH inhibition → motor-axon regeneration, NMJ restoration, force recovery; 15-PGDH aggregates define “target fibers” in human neurogenic myopathies · AI-extracted from PubMed abstract; PMC PDF not end-to-end verified ↩
dungan-2022-senolytic-muscle-hypertrophy · doi:10.1007/s11357-022-00542-2 · Dungan CM et al. · GeroScience 2022;44(4):1925-1940 · in-vivo (mouse) + human IHC · adult (5–6 mo) vs old (23–24 mo) C57BL/6J, synergist-ablation mechanical overload; senolytic D+Q 5/50 mg/kg days 7+10 of 14-day MOV · load-induced senescent cells emerge ~2 wk post-resistance-exercise in humans; old mice over-accumulate them and have blunted hypertrophy; D+Q gave old mice larger muscles/fibers · gap/needs-human-replication ↩
moiseeva-2023-senescence-atlas-muscle-regeneration · doi:10.1038/s41586-022-05535-x · Moiseeva V et al. · Nature 2023;613(7942):169-178 · scRNA-seq + senescent-cell enrichment · young + old mice · senescent cells repress muscle regeneration at all ages via an inflamed niche; clearance or CD36 neutralization accelerates regeneration in young AND old; transplant delays it; senescent cells also accumulate in human muscle ↩

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