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Re-doing Hayflick's 1965 research on cell division but with modern omics

hayflick limit senescence

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#1 CynthesisToday

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Posted 26 December 2023 - 04:19 PM

https://www.ncbi.nlm...elife-70283.pdf "Novel insights from a multiomics

dissection of the Hayflick limit"
"The data presented above across multiple data modalities to provide a clear connection between
senescent cells and myofibroblasts supported by independent observations at the level of DNA,
RNA, protein, transcription factor activity and metabolism (Figure 9). In light of these, replicative
senescence resembles a specialized subtype of EMT specific to the trans-differentiation of fibroblasts
into myofibroblasts (FMT) in response to wound healing (Lombardi et al., 2019; Gibb et al., 2020;
Hinz and Lagares, 2020). We hypothesize that during fibrotic disease states and/or age, fibroblasts
migrate to sites of micro-injuries. As these proliferating fibroblasts become replicatively aged, they
are triggered (by DNA damage or other insults) to rewire their metabolism to induce FMT via active
epigenetic reorganization (NNMT- SAM/NAD sink). It is important to note here that the in vitro DNA
damage here arises primarily from telomere erosion documented by the observation that our hTERT
control cultures do not exhibit the same changes. However, genotoxic stress in vivo may originate
from a variety of endogenous and environmental sources e.g. reactive oxygen species, replication
stress, chemical exposure etc."
The NNMT-SAM/NAD sink (depletion of SAM locally and redirection of the NAD cycle into a "dead-end")
is a new insight from Hayflick limit work and is reproduced in other research:
"These results are consistent with NNMT’s reported role as global epigenetic regulator through its
methylation sink activity (Komatsu et al., 2018; Eckert et al., 2019; Pissios, 2017; Ulanovskaya et al., 2013)."

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#2 QuestforLife

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Posted 16 January 2024 - 10:31 AM

I discussed this paper in April 2022 over in the Telomere section of this forum, which is the proper place for discussion of this paper. 





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#3 CynthesisToday

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Posted 16 January 2024 - 02:43 PM

No worries. I'll leave everything to you as I'm not re-upping. Enjoy!

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