This is not meant to be a comprehensive post. I wrote one of those a few months ago, but somehow it was deleted when trying to post, and I haven't re-written it. This is actually a lightly edited version of an email I wrote for my late-80s godmother and her doctor.
Here's the teaser:
Line-1 or L1 is an endogenous retrovirus which is in all humans (and all or almost all mammals). There are many copies of this virus in our genome but only about 15 copies (reference on request) are thought to be able to become active. Once they become active, they start causing mutations by inserting copies of themselves randomly into our genes. This can cause cancer and cellular senescence.
L1 is normally prevented from doing this by SIRT6 which is an enzyme that covers the places in the DNA that encode for L1 and stops it from replicating (it is associated with the histones). SIRT6 is NAD dependent and has reduced activity in aging.
References:
L1
L1 drives IFN in senescent cells and promotes age-associated inflammation.
SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age.
Long Interspersed Nuclear Elements 1 (LINE1): The chimeric transcript L1-MET and its involvement in cancer.
The quick summary of what I'm recommending is:
- Sublingual NMN
- 5 days a week
- Fisetin
- 1 day a week
https://www.iherb.co...ggie-Caps/43592
- Blackcurrant extract - contains polyphenols that are good for you, including one that may help to prevent genetic damage (see more below)
- twice a day
Details
1) Increase NAD+
NAD+ decreases with age, and not having as much NDA+ has a lot of bad effects including:
- Less ATP generation, less energy
- Less energy for organ function
- Less energy for intracellular functions such as DNA repair
- Less energy for NAD dependent enzymes such as SIRT6 (discussed in more detail later)
References:
Therapeutic potential of boosting NAD+ in aging and age-related diseases
Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice
Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects.
Supplement:
Sublingual nicotinamide mononucleotide (NMN). NMN is a vitamin B3-related compound and the immediate precursor of NAD:
Safety information (related compound - precursor of this compound):
2) Get rid of (some) senescent cells
As cells get older, some percentage of them become senescent. Senescent cells not only don't do what they are supposed to do, they also secrete inflammatory compounds and could transform into cancer cells. They are supposed to die on their own, but don't because they become less responsive or unresponsive to the signals that should tell them to die (apoptosis signals).
References:
Cellular senescence: when bad things happen to good cells
Aging, Cellular Senescence and Cancer:
Supplement:
Fisetin is a bioflavonoid found in strawberries.
Supplement information:
Fisetin is a senotherapeutic that extends health and lifespan.
Dietary flavonoid fisetin for cancer prevention and treatment.
3) Stimulate SIRT6 to inhibit LINE-1 retrotransposon activity
Line-1 or L1 is an endogenous retrovirus which is in all humans (and all or almost all mammals). There are many copies of this virus in our genome but only about 15 copies are thought to be able to become active. Once they become active, they start causing mutations by inserting copies of themselves randomly into our genes. This can cause cancer and cellular senescence.
L1 is normally prevented from doing this by SIRT6 which is an enzyme that covers the places in the DNA that encode for L1 and stops it from replicating (it is associated with the histones). SIRT6 is NAD dependent (see 1) above) and has reduced activity in aging.
Besides increasing NAD+, SIRT6 activity can also be enhanced by cyanidins, like the ones found in blackcurrants.
References:
L1
L1 drives IFN in senescent cells and promotes age-associated inflammation.
SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age.
Long Interspersed Nuclear Elements 1 (LINE1): The chimeric transcript L1-MET and its involvement in cancer.
Blackcurrant
Natural polyphenols as sirtuin 6 modulators.
Cyanidin ameliorates the progression of osteoarthritis via the Sirt6/NF-κB axis in vitro and in vivo.
Supplement:
- Blackcurrant extract containing cyanidin-3-rutinoside and other cyanidins
https://www.iherb.co...-Formulas/15600
https://www.iherb.co...-Formulas/15600
Supplement information:
Anthocyanins from Black Currants (Ribes nigrum L.)
