It seems that telomeres (special repeating units of DNA sequences at the end of our chromosomes) hold one of the keys to biological aging. In fact, telomere length has become useful as a biomarker of cellular aging. Once telomeres reach a critically short length, further cellular replications are prevented, leading to aging (senescence) of the cell. These senescent cells eventually accumulate or die. Senescent cells no longer contribute to active tissue maintenance and may even harm the normal function of that organ.
Like the burning of a fuse, telomeres steadily shorten every time a cell replicates itself. A study from The Lancet evaluating telomere length on a group of individuals age 60 and over found that those with shorter telomeres had a 3.18-fold higher mortality rate from heart disease and an 8.54-fold higher mortality rate from infectious disease.
Studies show plenty of triggers that accelerate telomere shortening, including oxidative stresses, inflammation, and obesity. Shortened telomeres are found in people with age-related disorders such as cardiovascular disease, diabetes, neurodegeneration, and osteoporosis. Not surprisingly then, the search is on for ways to preserve telomere length in normal cells, with the aim of sustaining cellular youth and healthy functioning.
Naturally, there is intense interest in any interventions that can lengthen telomere length, and so slow or even maybe reverse some aging processes. Cells naturally contain an enzyme called telomerase, which adds new DNA to the ends of telomeres, helping to keep them long enough to support cellular activities. In the past few years, scientists have accumulated an impressive array of evidence showing that one way of supporting healthy, long telomeres is to get an adequate intake of vitamins.There is now intriguing evidence demonstrating how supplemental vitamins can preserve telomere length and sustain more youthful cell functions.
B Vitamins Preserve Telomere Length
The B vitamins, including vitamins B6, B12, and folate, are essential factors in the metabolism of the molecules that make up DNA. Their importance is therefore critical in supporting normal cellular replication. Low levels of B vitamins are common in aging adults, and are closely associated with risk for developing age-related diseases.
It has long been known that B vitamin supplementation reduces homocysteine levels, and it was recently shown that people whose B vitamin levels are low have shorter telomeres. B vitamins are necessary for normal disposal of homocysteine, which accumulates under conditions of B vitamin deficiency. Homocysteine is a molecule associated with increased cardiovascular disease risk and poor blood vessel function. Both elevated homocysteine levels and diminished B vitamin levels are closely associated with premature shortening of telomeres, leading to accelerated cellular aging. Therefore, homocysteine-induced telomere shortening may be the central connection between B vitamin deficiency, high homocysteine levels and cardiovascular disease.
Taken together, these findings suggest that keeping B vitamins at adequate levels is an effective means of both lowering toxic homocysteine levels and supporting longer telomeres. NMN and NAD+ (see below) are also an important part of this process.
Vitamin D Promotes Telomerase Activity
A molecular link has been found between vitamin D and DNA repair an action required for maintenance of telomere length. Higher plasma vitamin D levels have been associated with longer telomeres.19 These findings have triggered other studies of vitamin D and its role in telomere function.
For example, patients undergoing hemodialysis for kidney failure have both decreased telomere length and lower vitamin D levels compared with healthy controls. But dialysis patients treated with vitamin D3 were shown to have longer telomeres than untreated patients, potentially explaining the beneficial health effects of supplementation in these individuals.
In a more generalized study, vitamin D supplementation in a group of overweight Americans, at a dose of 2000 IU/day, increased subjects' telomerase activity by more than 19%. This finding suggests that vitamin D plays an important role in supporting telomere lengthening and as a result has antiaging potential.
Vitamin C
Vitamin C can work to slow cardiovascular aging by preserving telomere length.
A dramatic demonstration of the value of vitamin C's role in aging-deceleration was provided by a 2016 study of cellular model of Werner Syndrome, a premature aging disorder. After testing numerous compounds for their ability to slow or reverse the rapid aging, scientists identified vitamin C as the most efficient "rescue" for many premature aging characteristics of the cells. Treated cells showed longer telomeres, reduced secretion of inflammatory cytokines, and improved integrity of their cellular nuclei, all features of much younger cells. Indeed, in a mouse model of Werner Syndrome, vitamin C rescued aging cells from premature death by altering expression of genes involved in the maintenance of DNA integrity.
NMN and NAD
Biosynthesis and regulation of nicotinamide adenine dinucleotide (NAD+) has recently gained a lot of attention, for good reasons. A systemic decline in NAD+ across many tissues is associated with all the hallmarks of aging. NAD+ can affect a variety of cellular processes, including metabolic pathways, DNA repair, and immune cell activity, both directly and indirectly. These cellular processes play a vital role in maintaining homeostasis, but as people get older, their tissue and cellular NAD+ levels decrease, and this drop in NAD+ levels has been connected to a number of age-related disorders. By restoring NAD+ levels, several of these age-related disorders can be delayed or even reversed.
NMN is a potent precursor for NAD+, synthesized from vitamin B3 in the form of nicotinamide. For years, it was thought that NMN was unable to enter cells on its own. It was thought necessary to convert NMN to nicotinamide riboside (NR), a different NAD+ precursor. NR would then enter cells, and be converted back to NMN. Yet no one could explain the fast pharmacokinetics the surprising speed with which it moved from the gut to the bloodstream and then tissues throughout the body. Animal experiments had already proven that this entire journey takes place in a matter of minutes—too fast for multiple biochemical transformations. In 2019 groundbreaking research showed that NMN has a unique and dedicated transporter (Slc12a8) that can move the molecule quickly across the cell membrane and into the cell where it can be transformed rapidly into NAD+.3 The researchers report that this NMN transporter is critical for aging individuals; as NAD+ levels fall with age, levels of this transporter are upregulated so that more NMN can enter cells and enrich levels of NAD+.
These new findings suggest that, due to NMN’s critical role in repleting NAD+, the body has more than one route of bringing it into the cell—both directly with its own transporter, and by moving NR into the cell and then transforming NR into NMN. Supplementing with NMN may improve adult human metabolism, rendering it more like that of someone ten or twenty years younger. In animal studies, NMN has enhanced NAD+ biosynthesis in pancreas, adipose, heart, eyes, blood vessel, skeletal muscle, kidney tissues and more.
NMN has been shown to improve against age-associated physical decline, weight gain, energy decline, and decreased physical activity, without any obvious toxicity. NMN also suppresses age-related adipose tissue inflammation, enhances insulin secretion and insulin action, supports healthy mitochondrial function, improves neuronal function in the brain, stimulates new blood vessel
NMN has been shown to help protect against diabetes, Alzheimer disease, endothelial dysfunction, and inflammation. They also reverse gut dysbiosis and promote beneficial effects at intestinal and extraintestinal levels.
NAD+ has a myriad of effects in our cells, including enabling the proper functioning of sirtuins, enzymes that protect our DNA and regulate the epigenome, and helping PARPs to do their job, which is repairing damaged DNA.
Trimethylglycine (TMG)
TMG is a methyl donor that supports the action of NMN and the liver. TMG provides significant methylation support by donating three methyl groups. Methylation is needed by the ‘longevity’ enzymes known as the sirtuins, which depend on NAD+ and which require the methylation of nicotinamide (NAM), a form of vitamin B3. The sirtuin family is thought to delay fundamental aspects of aging and to be responsible, in great part, for the cardiometabolic benefits of lean diets and exercise. Nicotinamide (NAM) has been shown to consume a significant amount of TMG when being methylated by the body.
Curr Nutr Rep 2023 Sep;12(3):445-464. doi: 10.1007/s13668-023-00475-y.
Mol Biol Rep 2022 Oct;49(10):9737-9748. doi: 10.1007/s11033-022-07459-1. Epub 2022 Apr 20.