Conversational learning transcripts below that reflects the online journal club interactions and selective sampling and critical appraisal of the journal published study content and the camaraderie:
[8/27, 1:19 AM] Sumit Global CBBLE:
Context: David is one of the pioneers of longevity research.
[8/27, 5:53 AM] Rakesh Biswas: Any links to the real paper for a proper appraisal in the PICO format?
[8/27, 10:15 PM] Sumit Global CBBLE: It's in the tweet (the link at the end)
[8/27, 10:19 PM] Rakesh Biswas: Can someone appraise it in the PICO format? @Aashita KIMS PG
[8/27, 10:26 PM] Aashita KIMS SR :
Sure sir
I’ll go through it
[8/27, 11:56 PM] Aashita KIMS SR:
Quoting,
To investigate the effect of TPE, we examined blood samples before and after rounds of this clinical procedure
P - 15 samples were included
I - Samples 1, 2, 4, 6, 7, and 8 were from old individuals
C - Samples 3 and 5 were from middle-aged people
( I’m assuming the remaining samples belong to the younger age group but they haven’t clearly mentioned their sample numbers)
[8/27, 11:56 PM] Aashita KIMS SR:
Quoting,
Changes in 8-OHdG levels after TPE.Oxidative DNA damage gradually decreases and becomes statistically lower by the last round, in all patients.
[8/27, 11:56 PM] Aashita KIMS PG: R0 is before TPE, R1 is 1 month afterwards and before the next round of TPE, and so on.
[8/27, 11:56 PM] Aashita KIMS PG:
Quoting,
C. TPE decreases p16 levels in PBMCs of old and middle-aged people,
D. TPE upregulates the markers of lymphoid genes (T cells, B cells, NK cells) in old PBMCs. E The lymphoid:myeloid ratio is increased by the rounds of TPE. The myeloid:NK ratio is downregulated by TPE. The ratios of lymphoid:CD68 and NK:CD68 are elevated by the rounds of TPE.
These data show a rejuvenation of the lymphoid/myeloid balance, suggesting an improved capacity for productive immune responses
[8/27, 11:56 PM] Aashita KIMS SR:
Quoting
Out of 507 proteins, 72 proteins were significantly different in their levels between the old and the young groups (> 1.75 fold change, p < 0.05). These 72 proteins were analyzed further in the longitudinal TPE datasets by heat mapping, which revealed a gradual rejuvenation of the age-specific systemic proteome by subsequent rounds of TPE. Principal component analysis confirmed that each R0 proteome (before the first TPE) was closer to the old control group than to the young control group and shifted from the old toward the young group with the rounds of TPE
[8/27, 11:56 PM] Aashita KIMS SR :
Quoting,
We also determined whether repetitive TPE may regulate the complement system including C3 and C1q, which play a key role in immune responses and also participate in non-immune crosstalks of cell–cell signaling pathways
[8/27, 11:56 PM] Aashita KIMS PG: In our analysis, 13 proteins were related to the negative regulation of apoptosis and the levels of these proteins were higher in the old group than in the young. Consistent with better tissue homeostasis, the levels of these apoptotic inhibitors diminished over rounds of TPE, becoming closer to the young cohort
[8/27, 11:56 PM] Aashita KIMS SR:
Quoting,
Considering these observations, we decided to analyze systemic levels of TDP43, which is the trigger of several neurological pathologies and becomes increased in the blood of patients with ALS, Parkinson’s disease (PD), frontotemporal dementia (FTD), and AD
[8/27, 11:56 PM] Aashita KIMS SR:
Circulating TDP43 levels are higher in old than in young individuals
[8/27, 11:56 PM] Aashita KIMS SR:
Summary: (Quoting)
Among 15 samples post TPE the oxidative dna damage reduces by each round of TPE. TPE also increased the lymphoma myeloid balance basically improving the immune responses. It also regulates complement C3 and C1q. Circulating TDP43 were found to be higher in older ages but with TPE, TDP43 reduced gradually.
[8/27, 11:56 PM] Aashita KIMS SR:
Quoting,
The effect of repetitive TPE on aged blood. Aged blood has the characteristics of chronic inflammation (inflammaging), increased PBMC DNA damage and senescence, and immune deregulation, all changes that promote the high risk of diseases. TPE resets the systemic milieu to a younger state by rapidly and significantly diluting the age-elevated inhibitors of the canonical signaling pathways that regulate tissue maintenance and repair.
[8/28, 8:10 AM] Rakesh Biswas: Thanks. Also please share the direct link to the paper
[8/28, 8:19 AM] Rakesh Biswas: Thanks
So to critically appraise this @Sumit Global CBBLE , David Sinclair has currently just begun to show scientists looking at certain chemical changes demonstrable on Therapeutic plasma exchange (TPE) as reflected in his obtained outcomes that simply mention the chemical changes as a result of TPE but don't tell us what actually happened in terms of longevity in the participants who received TPE.
That may require a follow up of the same or more cohorts and one would also need to figure out the optimal frequency of TPE necessary to maintain the levels of the currently assumed healthy chemical balance.
In essence this was a phase 2 study that shows promise but there's a long way ahead
[8/28, 8:24 AM] Sumit Global CBBLE: Interesting, thanks.
Regarding you question, as I've previously stated: DNA damage is directly linked to DNA methylation clock which is a standard ageing biomarker by now (until something cheaper and more reliable comes along).
So I guess we can say that TPE promises longevity (if this study replicates well in more trials)?
I agree regarding your points on the optimal frequency exploration.
[8/28, 8:26 AM] Sumit Global CBBLE:
And thanks for the detailed PICO analysis @Aashita KIMS PG
[8/28, 8:27 AM] Sumit Global CBBLE: Thanks for simplifying the appraisal! 🙏
[8/28, 8:30 AM] Rakesh Biswas: Yes it's promising but too early to draw conclusions.
Standard biomarkers are never standalone and have only been provided assumed causal associations in relation to more palpable clinical determinants such as morbidity, mortality, longevity and we would need to look again critically at those papers that have drawn causal association between oxidative DNA and patient outcomes
[8/28, 8:32 AM] Rakesh Biswas: Thanks for sharing the paper and this journal club, which I shall be archiving.
Please tell our audience here a little bit about yourself. 🙂
[8/28, 8:37 AM] Sumit Global CBBLE: True, promising but not 100% confirmation.
Here's the catch-22 with aging - good trials would need to run for 200 years (or atleast 150 if parallelized) to be perfectly sure of the outcomes given that the trials would need to run atleast twice the lifespan (repeating promising studies, or starting more studies in parallel that promise improvement in biomarkers to run them in their full length).
So I guess, in our lifetimes we would need to rely on best biomarkers available that improve the well being of the species in a noticeable way.
Are there other ways to be sure?
About me in the next text ➡️
[8/28, 8:40 AM] Rakesh Biswas: Got the link to the original here https://link.springer.com/
[8/28, 8:52 AM] Sumit Global CBBLE: Sinclair's YouTube podcast is great!
[8/28, 8:54 AM] Rakesh Biswas: Please share that link too
[8/28, 8:55 AM] Sumit Global CBBLE: https://youtube.com/c/
[8/28, 8:56 AM] Rakesh Biswas: Please share a link to your online learning portfolio. It could be a LinkedIn profile or anything. @Aashita KIMS PG 's online learning portfolio is here👉https://ashiness3.
[8/28, 9:01 AM] Sumit Global CBBLE: https://youtube.com/channel/
I tried doing this thing where I learnt a new field from the experts - was fun. It's limited to the design field though.
[8/28, 9:09 AM] Sumit Global CBBLE: Sure sir. I'll tell the group about myself.
Hi all, I'm Sumit Srivastava, primarily a technologist with extremely diverse interests.
Every couple of years I pick a field that I know nothing about and immerse myself into it, learning from the best.
Then overtime, I gradually accumulate knowledge in that field while also picking up new fields subsequently.
This method has worked decently over the years for learning various different things.
I've started noticing that a most problems have simple and logical solutions, even though they may seem complex at the first glance.
I picked up the field of medicine as a challenge a few years ago after working on some interesting things in brain computer interfaces.
Now I love the field of medicine so much that I've started exploring interesting (and promising) sub fields of the vast knowledge available in medicine.
As a child I knew that the my innate nature was that of curiosity - asking a lot of questions.
I've tried to not let that die (it's super hard, because questioning everything comes at the cost of speed of doing things).
Over time, you learn to question the things that matter the most.
I've learnt that the best things to question are the things that people think are either "really obvious" or things that are "mostly unexplored".
I take my inspiration from an excellent paper called you and your research by Dr. Richard W. Hamming, a pioneer in computer science.
Even though I'm not a researcher - this is one of the most groundbreaking paper an ambitious individual can read in their lifetime (it's super long): https://medium.com/motivate-
The global CBBLE is a social network currently with 156 members and can be joined through this link : https://chat.whatsapp.com/
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