Why NAD+ Declines during Aging: It’s Destroyed
Eduardo Chini and colleagues address an open question in biogerontology: why do NAD+ levels fall as we age? They show that the major culprit is an NADase called CD38 whose levels rise during aging. Their results also add to the body of evidence indicating that loss of SIRT3 activity in mitochondria is a cause of age-related metabolic decline
So as SIRT3 falters, the mitochondria die. However evidence shows ALCAR is able to restore SIRT3 expression.
Treatment with the AMPK agonist AICAR or the antioxidant agent acetyl-l-carnitine (ALCAR) restored SIRT3 expression and activity, improved renal function, and decreased tubular injury in WT animals, but had no effect in Sirt3-/- mice.
In cultured human tubular cells, cisplatin reduced SIRT3, resulting in mitochondrial fragmentation, while restoration of SIRT3 with AICAR and ALCAR improved cisplatin-induced mitochondrial dysfunction. Together, our results indicate that SIRT3 is protective against AKI and suggest that enhancing SIRT3 to improve mitochondrial dynamics has potential as a strategy for improving outcomes of renal injury.
https://pubmed.ncbi....h.gov/25607838/
Not only that but carnitine is literally the key to mitochondria being able to recieve nourishment. It is carnitine's job to shuttle nutrients in and waste products out of the mitochondria.
L-Carnitine is a naturally occurring substance required in mammalian energy metabolism that functions by facilitating long-chain fatty acid entry into cellular mitochondria, thereby delivering substrate for oxidation and subsequent energy production. It has been purposed that L-carnitine may improve and preserve cognitive performance, and may lead to better cognitive aging through the life span, and several controlled human clinical trials with L-carnitine support the hypothesis that this substance has the ability to improve cognitive function. We further hypothesized that, since L-carnitine is an important co-factor of mammalian mitochondrial energy metabolism, acute administration of L-carnitine to human tissue culture cells should result in detectable increases in mitochondrial function. Cultures of SH-SY-5Y human neuroblastoma and 1321N1 human astrocytoma cells grown in 96-well cell culture plates were acutely administered L-carnitine hydrochloride, and then, mitochondrial function was assayed using the colorimetric 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt cell assay kit in a VERSAmax tunable microplate reader. Significant increases in mitochondrial function were observed when human neuroblastoma or human astrocytoma cells were exposed to 100 nM (20 μg L-carnitine hydrochloride/L) to 100 μM (20 mg L-carnitine hydrochloride/L) concentrations of L-carnitine hydrochloride in comparison to unexposed cells, whereas no significant positive effects were observed at lower or higher concentrations of L-carnitine hydrochloride. The results of the present study provide insights for how L-carnitine therapy may significantly improve human neuronal function, but we recommend that future studies further explore different derivatives of L-carnitine compounds in different in vitro cell-based systems using different markers of mitochondrial function.
https://pubmed.ncbi....h.gov/24005823/
But what nutrients does the mitochondria need? As it turns out it burns fatty acids, but a specific fatty acid is it favorite food - stearic acid.
Dietary stearic acid regulates mitochondria in vivo in humansAbstract
Since modern foods are unnaturally enriched in single metabolites, it is important to understand which metabolites are sensed by the human body and which are not. We previously showed that the fatty acid stearic acid (C18:0) signals via a dedicated pathway to regulate mitofusin activity and thereby mitochondrial morphology and function in cell culture. Whether this pathway is poised to sense changes in dietary intake of C18:0 in humans is not known. We show here that C18:0 ingestion rapidly and robustly causes mitochondrial fusion in people within 3 h after ingestion. C18:0 intake also causes a drop in circulating long-chain acylcarnitines, suggesting increased fatty acid beta-oxidation in vivo. This work thereby identifies C18:0 as a dietary metabolite that is sensed by our bodies to control our mitochondria. This could explain part of the epidemiological differences between C16:0 and C18:0, whereby C16:0 increases cardiovascular and cancer risk whereas C18:0 decreases both.
So mito love C:18 fatty acid, ie stearic acid. The food highest in concentration of stearic acid is cocoa butter.
So my protocol consists of ALCAR and cocoa butter for the above reasons. So just gobble down some ALCAR caps right? Wrong.
First off all amino acids compete with each other for absorption. For highest absorption you must take aminos alone with no other protein intake. Secondly there is a way to greatly increase the penetration of ALCAR into the muscle tissues - insulin. when you take ALCAR with carbs, it create an insulin spike. The insulin then drives the ALCAR deep into the tissues.
http://citeseerx.ist...=rep1&type=pdf
Carbohydrate ingestion augments L-carnitine retention in humans
The present study aimed to investigate whether an increase in whole body carnitine retention can be achieved through L-carnitine feeding in conjunction with a dietary-induced elevation in circulating insulin. On two randomized visits (study A), eight men ingested 3 g/day L-carnitine followed by 4 500-ml solutions, each containing flavored water (Con) or 94 g simple sugars (glucose syrup; CHO). In addition, 14 men ingested 3 g/day L-carnitine followed by 2 500 ml of either Con or CHO for 2 wk (study B). Carbohydrate ingestion in study A resulted in a fourfold greater serum insulin area under the curve when compared with Con (P 0.001) and in a lower plasma TC concentration throughout the CHO visit (P 0.05). Twenty-four-hour urinary TC excretion in the CHO visit was lower than in the Con visit in study A (155.0 10.7 vs. 212.1 17.2 mg; P 0.05). In study B, daily urinary TC excretion increased after 3 days (65.9 18.0 to 281.0 35.0 mg; P 0.001) and remained elevated throughout the Con trial. During the CHO trial, daily urinary TC excretion increased from a similar basal value of 53.8 9.2 to 166.8 17.3 mg after 3 days (P 0.01), which was less than during the Con trial (P 0.01), and it remained lower over the course of the study (P 0.001). The difference in plasma TC concentration in study A and 24-h urinary TC excretion in both studies suggests that insulin augmented the retention of carnitine in the CHO trials.
NOw in that study they use simple syrup for carb source. I don't drink that stuff, instead I use high carb fruits like dates, bananas or apples.
The Protocol
On empty stomach take
3 - 5 grams ALCAR
High carb fruit (date/banan/apple)
1 gr Cocoa butter
Then wait for that to absorb before eating any protein source at all. Wait at least 20 - 30 minutes.
Thats it! that is the protocol. I do that about 2 - 3 times a week and believe it really gives me great energy. My skin seems to have improved since starting this formula, less line and wrinkles look smoother. I also take nicotinamide most day of the week. I have been on this protocol for about 3 months so far and love it. I plan to continue indefinitely.
Edited by Phoebus, 05 January 2022 - 02:36 AM.