Microarray screening revealed that epigenetic downregulation of the nuclear-coded GCAT gene, which is involved in glycine production in mitochondria, is partly responsible for these aging phenotypes. Treatment of elderly fibroblasts with glycine effectively prevented the expression of these aging phenotypes. __ http://www.nature.com/articles/srep10434
Researchers at the University of Tsukuba in Japan appear to have discovered one mechanism for mitochondrial ageing — which they suggest can be fairly easily reversed.
While the elderly group had reduced respiration, in accordance with the current theory, there was, however, no difference in the amount of DNA damage between the elderly and young groups of cells. This led the researchers to propose that another form of genetic regulation, epigenetic regulation, may be responsible for the age-associated effects seen in the mitochondria.
We try to avoid any recommendations that might be misconstrued as the unauthorised practise of medicine. However, we do suggest for those considering taking glycine supplements as a result of reading the linked articles, that they consider taking tri-methyl glycine (TMG) instead. We leave finding the reasons for this suggestion as an exercise for the reader.
Whether or not this process could be a potential fountain of youth for humans and not just human fibroblast cell lines still remains to be seen, with much more testing required. However, if the theory holds, glycine supplements could one day become a powerful tool for life extension. More
Senolytic Substances for Eliminating Senescent Cells
Senescent cells—cells that have stopped dividing—accumulate with age and accelerate the aging process. Since the “healthspan” (time free of disease) in mice is enhanced by killing off these cells, the scientists reasoned that finding treatments that accomplish this in humans could have tremendous potential. __ Scripps
Senescent cells appear to have a “toxic” effect on otherwise healthy tissues. Eliminating such cells appears to increase both fitness levels and lifespan — at least in mice.
Quercetin is one of the substances used in the study, and coincidentally is another supplement — in addition to TMG — which we at the Al Fin Institutes of Longevity have been known to recommend for the middle-aged and elderly.
The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age-related chronic diseases. Here, we describe the rationale for identification and validation of a new class of drugs termed senolytics, which selectively kill senescent cells… Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse BM-MSCs. The combination of dasatinib and quercetin was effective in eliminating senescent MEFs… In old mice, cardiac function and carotid vascular reactivity were improved 5 days after a single dose. Following irradiation of one limb in mice, a single dose led to improved exercise capacity for at least 7 months following drug treatment. Periodic drug administration extended healthspan in Ercc1−/∆ mice, delaying age-related symptoms and pathology, osteoporosis, and loss of intervertebral disk proteoglycans. These results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan. __ http://onlinelibrary.wiley.com/doi/10.1111/acel.12344/abstract
More on Senescent Cells
Cells become senescent in response to damage, toxic environments, or as an alternative to self-destruction when they reach the end of their replicative life span. Some are destroyed by the immune system, but enough remain and linger that many tissues are made up of a sizable proportion of senescent cells by late life. These cells behave badly, secreting compounds that alter surrounding cellular activities, spur chronic inflammation, and degrade the extracellular matrix that is fundamental to tissue properties such as elasticity or load-bearing strength. Even partial and uneven clearance of senescent cells has been demonstrated in animal studies to provide lasting benefits to health following a single treatment. Better and more comprehensive clearance should produce greater benefits. That, of course, requires the development of improved methods of clearance.
…. We show that ABT263 selectively kills SCs in culture in a cell type- and species-independent manner by inducing apoptosis. Oral administration of ABT263 to either sublethally irradiated or normally aged mice effectively depleted SCs, including senescent bone marrow hematopoietic stem cells (HSCs) and senescent muscle stem cells (MuSCs). Notably, this depletion mitigated TBI-induced premature aging of the hematopoietic system and rejuvenated the aged HSCs and MuSCs in normally aged mice. Our results demonstrate that selective clearance of SCs by a pharmacological agent is beneficial in part through its rejuvenation of aged tissue stem cells. Thus, senolytic drugs may represent a new class of radiation mitigators and anti-aging agents. __ https://www.fightaging.org/archives/2015/12/news-of-another-potential-family-of-senolytic-drugs-for-clearance-of-senescent-cells-in-aging.php
A Different Perspective on Treating Ageing
… curing all cancers, for example, although desirable, merely replaces cancer with other chronic morbidities such as Alzheimer’s, cardiovascular diseases, metabolic diseases, and so on. By contrast, in numerous laboratory animal models, including some studies in nonhuman primates and humans, interventions based on manipulations of nutrient sensing and cellular metabolism have shown not only longevity extension but also significant postponement of multiple age-related diseases (including cancer, Alzheimer’s, cardiovascular, and metabolic diseases). This, therefore, is close to, or achieves, health-span extension. __ Longevity Dividend
Other unconventional approaches to anti-ageing might include telomerase manipulation, a variety of mitochondrial rejuvenation / reprogramming techniques, increasingly sophisticated approaches to replacing damaged cells with fresh young cells, better in situ tissue and whole organ replacements, and improved “function replacement” technologies, or advanced cyborg tech — artificial limbs, sensory organs, muscles, bones, and even artificial internal organs. Most of us still prefer tissues and organs made of living cells, but in the future, who knows?
3D printing will be used to create living replacement tissues and organs, and to create artificially functional replacement parts.
3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology. __ https://www.ncbi.nlm.nih.gov/pubmed/25093879
Expect better anti-ageing drugs to be developed (if not approved) within a 5 to 10 year frame. Stem cell therapies will become more popular — even if one must travel to India, Mexico, or Thailand to obtain them. Pioneering telomerase therapies are popping up in Latin America.
National borders will be unable to block the movement of drugs, therapies, and new unconventional approaches to longevity.
In general, it is best not to expect too much. Still, if you pay attention and play your cards right, you may be able to extend your healthy years. But first, make your life count for something important.