Scientific and medical journal publications and studies in ageing and longevity.
Oxidative stress, inflammatory cytokines and body composition of master athletes: The interplay
https://link.researcher-app.com/Phic
– via Researcher (@ResearcherApp)
Oxidative stress, inflammatory cytokines and body composition of master athletes: The interplay
https://link.researcher-app.com/Phic
– via Researcher (@ResearcherApp)
We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.
“These studies demonstrate an important link between the [pathological] accelerated ageing process and normal aging, and also expose the CSB protein as a key factor against cellular ageing” concludes Dr. Ricchetti.
https://medicalxpress.com/news/2019-12-identification-key-protein-linked-ageing.html
“Analysis of these data demonstrates that pineal peptides (epithalamin and epithalon) have a more pronounced geroprotective effect on the thymus as compared with those of the thymus peptides (thymalin and thymogen) on the pineal gland.”
https://www.mendeley.com/catalogue/specific-features-pineal-glandthymus-relationships-during-aging/
“The expression of this gene led to the appearance of telomerase activity in the fibroblasts, elongation of telomeres (to the size characteristic of the embryonic cells), and immortalization.”
“While these results reveal some heterogeneity in the reprogramming process with respect to telomere length, human somatic cells reprogrammed to pluripotency generally displayed elongated telomeres that suggest that they will not age prematurely when isolated from subjects of essentially any age.”
https://www.mendeley.com/catalogue/telomere-dynamics-human-cells-reprogrammed-pluripotency/
“Aging is an important risk factor for several human diseases such as cancer, cardiovascular disease and neurodegenerative disorders, resulting from a combination of genetic and environmental factors (e.g., diet, smoking, obesity and stress), which, at molecular level, cause changes in gene expression underlying the decline of physiological function. Epigenetics, which include mechanisms regulating gene expression independently of changes to DNA sequence, regulate gene expression by modulating the structure of chromatin or by regulating the binding of transcriptional machinery to DNA. Several studies showed that an impairment of epigenetic mechanisms promotes alteration of gene expression underlying several aging-related diseases. Alteration of these mechanisms is also linked with changes of gene expression that occurs during aging processes of different tissues. In this review, we will outline the potential role of epigenetics in the onset of two age-related pathologies, cancer and cardiovascular diseases.”
“Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.”
“The SMART App serves as a new approach for users, especially wet-bench scientists with no programming background, to analyze the scientific big data and facilitate data mining. The SMART App is available at http://www.bioinfo-zs.com/smartapp.”
https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-019-0316-3
“A new clinical trial found that a combination of Growth Hormone, DHEA & Metformin helped to restore the size of the thymus gland and reverse biological age (epigenetic age via the GrimAge test).”
➢ Link to study:
Fahy, G. M., Brooke, R. T., Watson, J. P., Good, Z., Vasanawala, S. S., Maecker, H., et al. (2019). Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell, 18(6), 421–12. http://doi.org/10.1111/acel.13028
https://highintensityhealth.com/growth-hormone-dhea-metformin-in-aging-clinical-study/
“Previously, the only biochemical pathway that was known to be activated by metformin was the AMPK pathway, which Shaw discovered stalls cell growth and changes metabolism when nutrients are scarce, as can occur in cancer. But the scientists believed more pathways than AMPK might be involved.
The scientists developed a novel screening platform to examine kinases, the proteins that transfer phosphate groups, which are critical on/off switches in cells and can be rapidly flipped by metformin. Using this technology, the researchers were able to decode hundreds of regulatory “switch-flipping” events that could affect healthy aging.”
https://medicalxpress.com/news/2019-12-diabetes-drug-unexpected-broad-implications.html
“Ageing and many diseases are partly driven by the accumulation of damaged cells that no longer divide. It emerges that these senescent cells can be eradicated in mice using a drug that interferes with the activity of the protein FOXO4.
If cells incur too much damage, they undergo either a self-elimination process known as apoptosis or a self-disabling process called senescence. Senescent cells can be long-lived, and so accumulate in aged and damaged organs1. The elimination of senescent cells is known2,3,4,5,6 to increase healthy lifespan and reduce the severity of age-related diseases in mice. Writing in Cell, Baar et al.7 expand our understanding of this phenomenon. They report that senescent cells depend on the transcription factor forkhead box protein O4 (FOXO4) for their survival, and show in mouse models that both age-associated defects and tissue dysfunction caused by chemotherapy can be reversed by pharmacologically perturbing the function of this protein.
Senescent cells forcibly block their own capacity to proliferate while programming themselves to secrete signalling molecules — a phenomenon known as the senescence-associated secretory phenotype (SASP). It has been proposed8,9 that the normal function of the SASP is to restore tissue function in two ways: first, by stimulating less-damaged neighbouring cells to engage in tissue repair; and second, by attracting inflammatory cells to eliminate senescent cells and turn off SASP-mediated signals. However, this restorative process may fail when the extent, duration or frequency of damage exceeds repair capacity, or when reparative and inflammatory cells become unresponsive to the effects of the SASP. The end result is an aberrant accumulation of senescent cells that, contrary to their initial purpose, aggravate tissue dysfunction.” Serrano, M. Tools to eliminate senescent cells. Nature545, 294–295 (2017) doi:10.1038/nature22493
Polygonum multiflorum Thunb. (PMT, Polygonaceae family, Figure 1)), well known as He shou wu in China and Fo-ti in North America,[5] is one of the most popular perennial Chinese traditional medicinal vine-like herbs, officially listed in the Chinese Pharmacopoeia.[6] Various parts of the plants were utilized for different medicinal purposes. The leaves [Figure 2a], root tuber [Figure 2b] and rhizomes [Figure 2c] of this plant have been used as tonic and anti-aging agents[7,8,9,10,11,12] whereas the stem [Figure 2d] is used to alleviate insomnia and even to have an antidiabetic therapeutic activity as well.[13,14,15] Figure 1 Polygonum multiflorum Thunb Figure 2 Photos of (a) leaves, (b) tuber roots, (c) underground rhizomes and (d) stem from Polygonum multiflorum Thunb Laboratory studies and clinical practice have demonstrated that PMT possesses various biological and therapeutic actions, including anti-tumor,[16,17] antibacterial,[18] anti-inflammatory,[13] anti-oxidant,[19,20,21] anti-HIV,[22] liver protection,[23,24] nephroprotection,[25] antidiabetic,[15,26] anti-alopecia,[27,28] and anti-atherosclerotic activities.[29,30] It has been also reported to exert preventive activity against neurodegenerative diseases,[31,32,33,34,35] cardiovascular diseases and to reduce hyperlipidemia as well.[36,37]
Review of clinical studies of Polygonum multiflorum Thunb. and its isolated bioactive compounds
Emodin significantly inhibited the viability of and induced apoptosis in L02 cells in a dose- and time-dependent manner. In addition, emodin increased the number of GFP-LC3 puncta in L02 cells and upregulated the expression of LC3B-II compared to those in control cells. Furthermore, emodin significantly decreased the expression of p-PI3K, p-AKT and p-mTOR in a dose-dependent manner compared to that in control cells without altering the expression of PI3K, AKT and mTOR. Notably, cotreatment with emodin and 3-methyladenine (3-MA) or rapamycin significantly increased and decreased the apoptosis rate of L02 cells, respectively, compared to that of cells treated with emodin alone.
Emodin-induced autophagy against cell apoptosis through the PI3K/AKT/mTOR pathway in human hepatocytes. – PubMed – NCBI
Nicotinamide adenine dinucleotide (NAD), the cell’s hydrogen carrier for redox enzymes, is well known for its role in redox reactions. More recently, it has emerged as a signaling molecule. By modulating NAD+-sensing enzymes, NAD+ controls hundreds of key processes from energy metabolism to cell survival, rising and falling depending on food intake, exercise, and the time of day. NAD+ levels steadily decline with age, resulting in altered metabolism and increased disease susceptibility. Restoration of NAD+ levels in old or diseased animals can promote health and extend lifespan, prompting a search for safe and efficacious NAD-boosting molecules that hold the promise of increasing the body’s resilience, not just to one disease, but to many, thereby extending healthy human lifespan.
Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. – PubMed – NCBI
NAD+ is a pivotal metabolite involved in cellular bioenergetics, genomic stability, mitochondrial homeostasis, adaptive stress responses, and cell survival. Multiple NAD+-dependent enzymes are involved in synaptic plasticity and neuronal stress resistance. Here, we review emerging findings that reveal key roles for NAD+ and related metabolites in the adaptation of neurons to a wide range of physiological stressors and in counteracting processes in neurodegenerative diseases, such as those occurring in Alzheimer’s, Parkinson’s, and Huntington diseases, and amyotrophic lateral sclerosis. Advances in understanding the molecular and cellular mechanisms of NAD+-based neuronal resilience will lead to novel approaches for facilitating healthy brain aging and for the treatment of a range of neurological disorders.
NAD+ in Brain Aging and Neurodegenerative Disorders. – PubMed – NCBI
Human life extenssion via Telomerase activation and elongation of Telomeres
Epitalon is one of the very few substances which are able to activate Telomerase (telomere terminal transferase) enzyme in humans. Telomerase renews (elongates) the telomeres, which are responsible for protection of the human DNA from damage and cancer causing errors.
Treatment of aging cells in culture with Epithalon induced elongation of telomeres to the size comparable to their length during the early cell divisions. Epitalon treated cells with elongated telomeres made 10 extra divisions (44 passages) in comparison with the control and continued dividing. Thus, Epithalon prolonged the vital cycle of normal human cells due to overcoming the Heyflick cell division limit. (reference: V. Khavinson et all. in Bulletin of Experimental Biology and Medicine. June 2003, PMID: 12937682)
Epitalon used for Anti Aging
Epitalon decreases the age-related changes in immune and neuroendocrine systems, reduces the incidence of recurrent infections and chronic diseases. Long term clinical trials have shown that in patients with age-related pathology Epithalamin eliminates imbalance in prooxidation and antioxidation systems. (reference: N. Anisimov et all. Neuroendocrinology Letters, 2011, PMID: 11335874)
We show that the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, the mTOR complex 1 (mTORC1) inhibitor rapamycin, and the glycogen synthase kinase-3 (GSK-3) inhibitor lithium act additively to increase longevity in Drosophila
https://www.leafscience.org/a-triple-drug-combination-increases-lifespan/
To uncover more CRMs, Kroemer and his team now tested 200 compounds that belong to the same class of substances as spermidine and resveratrol. They first examined which of these substances show cellular reactions characteristic of elevated autophagy in rat and human cell cultures, while not being toxic to the cells. An agent called 3,4-dimethoxy chalcone (3,4-DC) stood out as the best candidate. A closer look at the exact mode of action of 3,4-DC revealed that it induces autophagy through a different pathway than spermidine and resveratrol.
https://www.sciencedaily.com/releases/2019/10/191021111842.htm
Although reduced physical activity during the day is widely seen as a harbinger of mortality in older people, fragmentation of physical activity — spreading daily activity across more episodes of brief activity — may be an earlier indicator of mortality risk than total amount of daily activity, according to a new study from scientists at the Johns Hopkins Bloomberg School of Public Health.
Fragmented physical activity linked to greater mortality risk — ScienceDaily
A triple drug combination has been used to extend the lifespan of fruit flies by 48% in a new study led by UCL and the Max Planck Institute for Biology of Ageing.
https://www.sciencedaily.com/releases/2019/09/190930161857.htm
Dr. David Sinclair’s book is truly an amazing resource that lays out the science behind why and how we age and how we can improve our health span and maybe even increase our lifespan.
The audio version on Audible is especially good with additional commentary and updates that didn’t make it to print.
The book is very affordable and there are things you could be doing right now to improve your health span and avoid or even eliminate disease.
https://lifespanbook.com?rh_ref=74f8f88c
” The decline in early life mortality since the 1950s has resulted in dramatic demographic shift towards aged population. Aging manifests as a decline in health, multiple organ dysfunction and increased vulnerability to diseases, which degrades quality of life. A verity of genetic and pharmacological interventions, mostly from non-vertebrate models, have been identified that can enhance lifespan. Whether these interventions extend healthspan, the disease free and functional period of life, has only sometimes been tested and is often a matter of debate. Human aging indices have been developed to assess elements of functional decline with aging (e.g. sarcopenia, cognitive function). However, corresponding comprehensive indices in mice are seldom applied to aging studies. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically-relevant healthspan measurements. Metabolism and aging are tightly connected and specific perturbations of nutrient-sensing pathways can enhance longevity in laboratory animals. Here we show that alpha-ketoglutarate (delivered in the form of a Calcium salt, CaAKG), a key metabolite in tricarboxylic (TCA) cycle that is reported to extend lifespan in worms, can significantly extend lifespan and healthspan in mice. AKG is involved in various fundamental processes including collagen synthesis and epigenetic changes. Due to its broad roles in multiple biological processes, AKG has been a subject of interest for researchers in various fields. AKG also influences several age-related processes, including stem cell proliferation and osteoporosis. To determine its role in mammalian aging, we administered CaAKG in 18 months old mice and determined its effect on the onset of frailty and survival, discovering that the metabolite promotes longer, healthier life associated with a decrease in levels of inflammatory factors. Interestingly the reduction in frailty was more dramatic than the increase in lifespan, leading us to propose that CaAKG compresses morbidity. “
https://www.biorxiv.org/content/10.1101/779157v1
https://www.ncbi.nlm.nih.gov/pubmed/24828042?fbclid=IwAR1a8Z8sHjZ_W8o2-z74et4afbGkO3xf5JqWzfGL2XCeFR1IyDdNaiIZsBQ
http://agingbiotech.info/companies/
“AMPK is an enzyme essential for maintaining energy balance. It consists of 3 proteins (called sub-units) that together create a functional enzyme. AMPK is expressed in various tissues, including the brain, liver, skeletal muscle, and fat cells. The net effects of AMPK activation include ketogenesis, stimulation of hepatic fatty acid oxidation, inhibition of cholesterol synthesis, triglyceride synthesis, and lipogenesis, and the stimulation of glucose uptake and skeletal muscle fatty acid oxidation.
AMPK is also an energy sensor. When activated in the proper tissues, it brings about a number of beneficial effects in the body. It improves insulin sensitivity, stimulates weight loss, enhances muscle performance, and reduces inflammation, among many other benefits. It also fosters healthy aging and is involved in multiple longevity pathways.”
AMPK Activator: A Complete Guide to AMP-activated protein kinase
a study published by the University of Wisconsin in July, 2019, scientists discovered that a rapamycin analog called DL001 inhibits mTOR without all the severe side effects, such as suppression of the immune system, glucose, or liver toxicity. Suppression of mTOR has been associated with better health and longer life. mTOR is activated by eating foods like red meat, so finding a way to suppress mTOR without all the harmful side effects would be a major breakthrough.
Scientists have known that mTOR is composed of two complexes, called mTORC1 and mTORC2. As it turns out, you only need to suppress one of them, mTORC1 to get all the positive longevity benefits associated with rapamycin. Suppressing mTORC2 is what has caused many of the negative side effects of rapamycin, so discovering that the rapamycin analog DL001 suppresses mTORC1 without suppressing mTORC2 is the breakthrough that may finally allow us to get the benefits of rapamycin without the severe side effects.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642166/
MIB-626 is a NAD+ precursor being developed with the help of David Sinclair’s lab. It is understood that this is the molecule that is touted to be even more effective than NMN and caused mice to run over 3km and break the lab treadmill.
It’s not yet available but one to really keep an eye on.
A very good interview with David Sinclair to explain the systems involved and how we can possibly manipulate them to increase health and lifespan