Nat Commun. 2018 Feb 23;9(1):800 Notes from the Lab:
This paper asks an important question of accumulation of somatic mutation with age, and tries to answer it well, giving suggestive data, but there are some caveats:
Long-term culture (50 days or more) results in accumulation of mutations in human primary myoblasts. There is no strong data in the paper on in vivo accumulation of mutations with age in muscle stem, satellite, cells or in myofibers. Differentiation of satellite cells to myoblasts is known to result in accumulation of DNA damage; and this is a physiologic response that may actually be needed or at least tolerated during differentiation, even in the young muscle and moreover, many other tissues (Trends Cell Biol. 2011 May; 21(5): 312–319. , Cousin, Plos One, 2013; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660529/).
Figure 2d (there does not seem to be statistical significance, based on overlapping and large error bars).
With differentiation from the long-term cultured myoblasts to myotubes, there seem to be more mutations in the old cultures. However, it is not clear if the “young” and “old” cultures were identically homogeneous at this point. Old cultures have notoriously more fibroblasts, which expand with time.
Figure 4C: SCC (i.e. the myoblast cultures) has more mutations than SKM in every panel, which suggests that the culture of primary myoblasts accumulates mutations as compared with derivation or normal differentiation of actual satellite cells.
Only a sub-population of cells (CD56high) was analyzed. Mutations in myoblasts were referenced by the WBC; however, accumulation of mutations in leukocytes is also expected with age, so it is not clear which cell type is a good reference for which other cell type.
Results show that for most loci there is no accumulation of mutations with age and for one locus (5) there is barely an increase with age (the magnitude is low and barely statistically significant). No age-specific mutations in exons and promoters were found.
Satellite cells have not been shown to accumulate mutations with age (either in mice or humans), so the correlation with lack of proliferation is misleading, because only terminally differentiated, non-dividing in vitro formed myotubes seem to accumulate mutations, based on reported findings. Plus, in people the decline in skeletal muscle maintenance and repair is noticeable at 40+ year of age, while in the paper 20-year old were compared with the 80-year old, so again, correlations between the in-culture differences and actual muscle stem cell performance in vivo does not seem to account for the age-specific deficit in muscle regeneration.
Summarily: Nowhere it is shown that actual human myofibers or muscle stem cells (satellite cells) accumulate mutations with age after 80 years of lifespan.