RE: The quest for elixir of life. Episode 5 - The tik-tok of telomeres

Superbly researched and conveyed.

Interestingly, I have just today read research that may impact your interest. It is notable that centenarians are far more likely to be smokers than not, which seems extremely counterintuitive to many unfamiliar with the nootropic and metabolic effects of nicotine.

"One of the key players involved in ATP production is the redox molecule Nicotinamide adenine dinucleotide (NAD). NAD is present in all living cells and is available in two forms: NADH and NAD+. Both forms are essential for proper cellular energy transfer, and insufficient amounts can result in mitochondrial dysfunction. NADH's function is to carry electrons in the mitochondria to facilitate ATP synthesis. Once NADH has donated those electrons, it becomes NAD+. NAD+ has been shown45 to increase the rate of DNA repair, stress resistance, and regulate cell apoptosis. Furthermore, NAD+ also restores tissue integrity, induces homoeostasis, and increases longevity of the cell46. The cell senses levels of NAD+ as a measure of mitochondrial energy production and rate of metabolism. For this reason, the amount of NAD+ converted actually plays a significant role in regulating the rate of ATP synthesis and cellular metabolism.47 Low levels of NAD+ reduce mitochondrial energy production, decrease the number of mitochondria in the cell48 and contribute significantly to muscular ageing processes.49 Interestingly, NAD+ also has the ability to alter gene expression by "switching off" genes associated with degenerative processes."

"To follow on, SIRT1 (sirtuin) is a NAD-dependent protein coded for by the SIRT1 gene that cannot function without NAD+. So when NAD+ levels decrease, SIRT1 levels also decrease, and vice versa. SIRT1 turns out to be one of the single most important enzymes in control of epigenetic expression, metabolism and longevity. Studies have shown that SIRT1 inhibits MTOR pathway signalling, increases leptin sensitivity51, increases T3 hormone sensitivity52, and also increases the skin's sensitivity to Vitamin D.53 SIRT1 also inhibits/switches off genes associated with inflammation54, blood sugar regulation, and body fat accumulation/storage."

"One study56 conducted by Cancer Research in 2012 showed:"

"SIRT1 activity was the most consistently and significantly up-regulated in smokers compared to non-smokers in all 4 datasets. While SIRT1 was activity correlated to smoking status, SIRT1 pathway activation was not significantly correlated with pack-years among smokers (p > 0.05; Spearman). Therefore, independent of cumulative exposure, SIRT1 activity is consistently up-regulated in smokers. This increase in SIRT1 activity may serve as a protective effect against oxidative stress and DNA damage induced by smoking."

This and more is published at sott.net, with copious cites available there.

Thanks!