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Naked mole-rats live nine times as long as similarly sized rodents, and are near immune to cancer. Researchers have for some years investigated the biochemistry of this species, in search of mechanisms that might be applied to improve health and longevity in other mammals, or form the basis for cancer therapies. Teams have looked into many different areas: mitochondrial function; better DNA repair; a greatly attenuated senescence-associated secretory phenotype; more efficient operation of cancer-suppression genes; and a heavier form of hyaluronan. Researchers here show that this heavier form of hyaluronan is protective of cells, and can produce this protective effect in human cells as well as naked mole-rat cells.

The longest-living rodent, the naked mole-rat (NMR) (Heterocephalus glaber), has a maximum lifespan of more than 30 years, which is fivefold greater than predicted by body mass. NMR does not show increase in mortality rates for at least 18 years, and seems to be protected from age-related deterioration such as metabolic decline, diabetes, and osteoporosis. These features indicate that NMR has evolved efficient anti-aging mechanisms. However, although NMR is increasingly appreciated as a model for aging research, how they resist aging processes remains largely unknown.

An important NMR-specific anti-cancer mechanism is early contact inhibition (ECI). Cultured NMR fibroblasts are hypersensitive to contact inhibition and stop proliferating at relatively low cell density in a hyaluronan (HA)-dependent manner. HA plays a role in supporting tissue structure and regulating cellular signaling pathways depending on its polymer length. Dynamic regulation of the amount and polymer length of HA is implicated in diverse biological processes including cell proliferation, cell migration, and inflammation. In healthy tissues, most of HA is of high-molecular-mass (HMM-HA). In pathological circumstances, significant fragmentation of HA occurs, giving rise to low-molecular-mass HA. NMR produces very-high-molecular-mass hyaluronan (vHMM-HA), much longer than HA in other mammalian species. However, it is still not clear whether HA of exceptionally high polymer length is functionally different from regular HMM-HA.

The observations that HA exhibits polymer length-dependent cytoprotective effect and that long-lived NMR produces vHMM-HA lead to a hypothesis that additional polymer length of NMR-HA confers superior cytoprotection that could contribute to the NMR's longevity. Here, we show that vHMM-HA has superior cytoprotective properties compared to the shorter HMM-HA. It protects not only NMR cells, but also mouse and human cells from stress-induced cell-cycle arrest and cell death in a polymer length-dependent manner.

The cytoprotective effect is dependent on the major HA-receptor, CD44. We find that vHMM-HA suppresses CD44 protein-protein interactions, whereas HMM-HA promotes them. As a result, vHMM-HA and HMM-HA induce opposing effects on the expression of CD44-dependent genes, which are associated with the p53 pathway. Concomitantly, vHMM-HA partially attenuates p53 and protects cells from stress in a p53-dependent manner. Our results implicate vHMM-HA in anti-aging mechanisms and suggest the potential applications of vHMM-HA for enhancing cellular stress resistance.

Link: https://doi.org/10.1...467-020-16050-w

View the full article at FightAging

[zorba990]

Looks like even the HMM versions can be absorbed orally (even mixed with cornstarch eeeewwwww):

Oral Administration of Polymer Hyaluronic Acid Alleviates Symptoms of Knee Osteoarthritis: A Double-Blind, Placebo-Controlled Study over a 12-Month Period
https://www.hindawi....wj/2012/167928/

"Abstract
This study was conducted to investigate the efficacy of oral hyaluronic acid (HA) administration for osteoarthritis (OA) in knee joints. Sixty osteoarthritic subjects (Kellgren-Lawrence grade 2 or 3) were randomly assigned to the HA or placebo group. The subjects in the HA group were given 200 mg of HA once a day everyday for 12 months, while the subjects in the placebo group were given placebo. The subjects in both groups were requested to conduct quadriceps strengthening exercise everyday as part of the treatment. The subjects’ symptoms were evaluated by the Japanese Knee Osteoarthritis Measure (JKOM) score. The symptoms of the subjects as determined by the JKOM score improved with time in both the HA and placebo groups. This improvement tended to be more obvious with the HA group, and this trend was more obvious with the subjects aged 70 years or less. For these relatively younger subjects, the JKOM score was significantly better than the one for the placebo group at the 2nd and 4th months after the initiation of administration. Oral administration of HA may improve the symptoms of knee OA in patients aged 70 years or younger when combined with the quadriceps strengthening exercise."

"2.2. Hyaluronic Acid

The hyaluronic acid used in this study was manufactured by kewpie Corporation (Tokyo) (Hyabest (J)). This HA had been shown to have a purity of 97% and a molecular weight of approximately 900,000, as determined by HPLC. The HA was mixed with an appropriate amount of cornstarch (Cornstarch IPW, Nihon Shokuhin Kako Co., Ltd., Tokyo) and was administered in a form of hard capsules, each containing 50 mg of HA. The capsules were manufactured by Aliment Industry Co., Ltd. (Tokyo)."

https://www.ncbi.nlm...les/PMC4281855/
Oral Intake of a Liquid High-Molecular-Weight Hyaluronan Associated with Relief of Chronic Pain and Reduced Use of Pain Medication: Results of a Randomized, Placebo-Controlled Double-Blind Pilot Study
"Abstract
The goal for this study was to evaluate the effects of daily oral intake of a consumable liquid fermentate containing high-molecular-weight hyaluronan, as well as to perform a basic evaluation of safety and tolerability. A randomized, double-blind placebo-controlled study design was used to examine the effects of oral intake of hyaluronan on chronic pain conditions. Safety assessment included a complete blood count with differential, blood chemistry and electrocardiogram. The study duration was 4 weeks, where three tablespoons (45 mL) product or placebo was ingested during the first 2 weeks, and two tablespoons (30 mL) was consumed during the last 2 weeks. Seventy-eight people between the age of 19 and 71 years enrolled, and 72 people completed the study. Statistical analysis was performed using the two-tailed independent t-test for between-group significance and using the paired t-test for within-group significance. A reduction in pain scores was seen after 2 weeks of consumption of both placebo (P<.1) and active (P<.065) product; the reduction was more pronounced in the group consuming the active test product. Using “within-subject” analysis, a highly significant reduction in chronic pain scores was seen after 2 weeks of consumption of three tablespoons of active product (P<.001), whereas only a mild nonsignificant reduction in pain scores was seen in the placebo group. During the reduced intake for the last 2 weeks of study participation, pain scores showed a slight increase. During the last 2 weeks, a significant increase in the quality of sleep (P<.005) and level of physical energy (P<.05) was seen. The pain reduction during the initial 2 weeks was associated with significant reduction in the use of pain medication (P<.05). Consumption of an oral liquid formula containing high-molecular-weight hyaluronan was associated with relief of chronic pain."

Edited by zorba990, 21 May 2020 - 03:11 PM.