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September & October 2024 Longevity Review Part 2
dietary restriction exosomes longevity
In a bid to finally catch up with these Longevity Reviews, I took the decision to combine the results for September and October. This led to a fair amount of hand wringing as I sought to include only the biggest and most important studies for those two months, but my final selection for the Highlights Sections sees us taking a look at the most comprehensive dietary restriction study in mice to date; how the rat lifespan record might have been broken with exosome treatment; how an inhibitor of hyaluronan synthesis increases lifespan in mice; how exercise intensity is more important than volume for mortality reduction and, in the Canadian Content Study, how a protector of neurons plays a greater role in lifespan.
As a result of this merger, the supplemental section is bigger than normal. I tried to condense it as much as possible, but there were just too many studies that had to be included. Therefore, as a brief taster, you’ll find in Lifestyle the link between cardiovascular health and cancer mortality; in Fasting, how eating late affects blood glucose; in Diet, how dietary diversity affects aging; in other Supplements, reviews of Hesperetin & NAC; in Metformin, how it slows down aging in non-human primates; in Epigenetics, reprogramming senescent cells extends mouse lifespan; in Genetics, the use of CRISPR to find new ways to rejuvenate brain stem cells; in Opinion, some new theories on aging; in Reproductive Health, how genistein can help with menopause; and finally, in Telomeres, how astragalus increased telomere length in a human trial. (To make these suggestions easier to find, I’ve marked them with ***)
NOTE: The original post was too long, so I have split the Supplemental Section in two to accomodate the limit.
Canadian Longevity Association News
The big news over the last two months is that we’ve opened up an online shop!
That’s right, just in time for Christmas, you have all your shopping needs sorted! LOL
But seriously, you can now help fund the CLA’s activities, while sporting our logo on a wide and growing range of apparel. Take a look at our shop and if there is anything missing that you’d like to purchase, then drop us a line and we’ll happily and quickly add it.
Link to the CLA’s Online Store
Please also follow, or join us on social media:
Twitter/X (I also have a personal account with more frequent longevity updates)
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Canadian Longevity Association YouTube Channel - where you can find video talk-throughs of these reviews.
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Previous newsletters can be found in the CLA Facebook Group, and also my Patreon account, which includes bonus material for supporters if you want to buy us a coffee.
Finally, we are always looking for more help or volunteers, regardless of your skill set or time availability. If you’d be interested in helping us, please fill out this Volunteer Registration Form.
Sep/Oct 2024 Highlights:
In the largest comparative study of different forms of dietary restriction in female mice, scientists from CALICO discovered some really interesting and puzzling results. They studied 20% and 40% caloric restriction, as well as 1 and 2 days a week fasting. The median and maximum respectively for each compared to the control were as follows: 20CR: 18% & 22%; 40CR: 36% & 38%; 1DF: 12% & 6%; 2DF: 11% & 15%.
The 40% caloric restriction mice were clearly the winners, but changes to their immune system might make them more susceptible to infection. Another big puzzle was that lower weight and fat was better in early life, but then reversed in late life. As the authors put it, “DR extends lifespan while decreasing body weight and fat mass, yet preserving body weight and fat mass is associated with longer lifespan. This paradox is a recurrent theme in this study.”
This is a really in depth and readable study, and I do recommend that you take a look at it.
Study probes how eating less can extend lifespan Full Text
A research group who have been following since they started out, and who I have covered several times in these highlights, have released their latest results. E5, a young blood plasma fraction mainly consisting of exosomes, was previously shown to reduce the epigenetic age and improve various biomarkers in rats. This new study, along with once again showing improved biomarkers and grip strength, takes it further by including lifespan. And, the result of that was that the median lifespan improved by 9.7% over controls. More tantalizingly, one of the rats potentially broke the rat lifespan record for this strain, dying at the age of 48 months, which was a 21.7% increase over the longest lived control rat!
This was a very small study, with only 8 rats in each group, however I believe this to have great potential. Especially as they used young plasma from a different species, in case pigs, which means that if it were to work in humans, there would not be an issue of supply or ethical considerations. In correspondence with the researchers, I was told that they have now moved on to larger animals, specifically beagle dogs, with so far positive results, including a 50% reduction in IL-6, which they intend to publish in the coming year. This time, to further prove the cross species applicability, they have used young blood plasma from horses. In addition, they plan to test it on old cats with chronic kidney disease next year as well. If these studies are successful, the next step will be into humans. Needless to say, my fingers are crossed as I impatiently await the results!
Exosomes Break Rat Lifespan Record Full Text
In this study, it was found that an inhibitor of hyaluronan (hyaluronic acid) synthesis, 4-MU, increased the average and maximum lifespan of male mice by more than 20%. It seemed to do this by reducing blood glucose and increasing insulin sensitivity. Interestingly, the mice weighed less despite eating the same amount of food. This was a very small study, but this molecule is already in human trials, where it has recently passed phase 2a for pulmonary hypertension. I will be watching out for this molecule in the future.
Hymecromone Promotes Longevity and Insulin Sensitivity in Mice Full Text
Taking data from 7.5K US adults who wore actigraphs to measure their physical activity and were followed for seven years to assess mortality risk, it was unsurprisingly found that a greater volume and intensity of exercise was associated with reduced risk of death. However, it appears that intensity is more important than volume. Also longer continuous bouts of exercise were better than the same amount of exercise broken down into smaller chunks. There is a really nice infographic at the beginning of the article which does a good job summarizing these findings, and is worth checking out.
*Exercise Intensity, Duration, and Amount All Matter Full Text
Canadian Content Study
From McMaster University, researchers led by Bhagwati Gupta, have discovered how MANF, a protein which helps to protect neurons, plays a greater role in cell survival by regulating protein folding and clumping, as well as autophagy, the recycling system in cells. Working with c.elegans worms, those which lacked MANF had shorter survival times, while those which had more of it had 21% greater lifespan, and survived stress better. MANF is found in all animals, including us, and could play a role in healthy longevity.
From correspondence with Bhagwati, he said their current research “explores the proteins that interact with MANF to mediate its function and how secreted MANF affects different tissues and neuronal cells. We are also investigating the dynamics of MANF expression to better understand its role in cellular processes.” We wish them luck!
Protein shakeup: Researchers uncover new function of a protein that may unlock age-related illnesses Abstract Preprint Full Text
Further Canadian content is indicated by CAN
Supplemental Section
Other Areas of Interest (in alphabetical order)
Ageing Clocks & other biomarkers of ageing
*CheekAge, a next-generation epigenetic buccal clock, is predictive of mortality in human blood Full Text
*A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank Full Text
*Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome Full Text
*There are multiple clocks that time us: Cross-sectional and longitudinal associations among 14 alternative indicators of age and aging Full Text
Blood Factors or other Heterochronic Transplantation
Hyaluronan and proteoglycan link protein 1 - a novel signaling molecule for rejuvenating aged skin Full Text
Cellular and transcriptomic changes by the supplementation of aged rat serum in human pluripotent stem cell-derived myogenic progenitors Full Text
Epigenetics & Cellular Reprogramming
Reprogramming Senescent Cells Extends Lifespan in Mice Abstract
Rejuvenating the Hippocampus With Metabolites Full Text
Neuronal Reprogramming Alleviates Alzheimer’s in Mice Full Text
Exosomes (small packets of information released by cells)
Young small extracellular vesicles rejuvenate replicative senescence by remodeling Drp1 translocation-mediated mitochondrial dynamics Full Text
Extracellular Vesicles to Fight Liver Fibrosis Full Text
Extracellular Vesicles for Treating Arthritis Full Text
Genetics including CRISPR
*Depletion of loss-of-function germline mutations in centenarians reveals longevity genes Full Text
CRISPR helps brain stem cells regain youth in mice Full Text***
Towards Fine-Tuned Control of Gene Expression Full Text
Lifespan Lengthening Interventions
Berberine extends healthspan and delays neurodegenerative diseases in Caenorhabditis elegans through ROS-dependent PMK-1/SKN-1 activation Full Text
Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells Full Text
Systems biology approaches identify metabolic signatures of dietary lifespan and healthspan across species Full Text
Microbiome
Effects of non-pharmacological interventions on gut microbiota and intestinal permeability in older adults: A systematic review: Non-pharmacological interventions on gut microbiota/barrier Full Text
Can longer lifespan be associated with gut microbiota involvement in lipid metabolism? Full Text
Impact of Mouthwash-Induced Oral Microbiome Disruption on Alzheimer's Disease Risk: A Perspective Review Full Text
Observational Studies
*Do people reach 100 by surviving, delaying, or avoiding diseases? A life course comparison of centenarians and non-centenarians from the same birth cohorts Full Text
*Delayed onset of cognitive terminal decline in later born cohorts: Evidence from a longitudinal study of two cohorts born 29-years apart
*Resilience among older adults with multimorbidity using the Connor-Davidson scale in the Canadian Longitudinal Study on Aging: health behaviour, socio-economic, and social support predictors Full Text CAN
*Cross-sectional and prospective associations between sleep health and multimorbidity in middle to older-aged adults: Results from the Canadian Longitudinal Study on Aging (CLSA) CAN
*Linking cognitive and behavioral reserve: Evidence from the CAN-PROTECT study Full Text CAN
*Younger epigenetic age is associated with higher cardiorespiratory fitness in individuals with airflow limitation Full Text CAN
*Association of Muscle Strength With All-Cause Mortality in the Oldest Old: Prospective Cohort Study From 28 Countries Full Text
*Impact of Alcohol Consumption on Lifespan: a Mendelian randomization study in Europeans Full Text
Opinion/Editorials/Theory
Defining an ageing-related pathology, disease or syndrome: International Consensus Statement Full Text
The impact of short-lived controls on the interpretation of lifespan experiments and progress in geroscience – through the lens of the “900-day rule” Preprint
*Have We Maxed Out on Life Expectancy Gains? Full Text
Five-factor theory of aging and death due to aging Full Text***
The evolution of ageing: classic theories and emerging ideas Full Text***
The Power of a Complex Systems Perspective to Elucidate Aging Full Text***
Other Ageing Biology
A New Atlas for Cellular Rejuvenation Full Text
Autodigestion From Gut Enzymes May Drive Aging Full Text
Microplastic exposure linked to accelerated aging and impaired adipogenesis in fat cells Full Text
Regenerative Medicine
Durable Muscle Extracellular Matrix Engineered with Adhesive Phenolic Moieties for Effective Skeletal Muscle Regeneration in Muscle Atrophy Full Text
Reproductive Health
Eggs from older mice regain youth when grown in young cells Abstract
New treatment extends ovarian function in older mice Abstract
*Testosterone and resistance training improved physical performance and reduced fatigue in frail older men: 1 year follow-up of a randomized clinical trial Full Text
*The association between age at natural menopause and risk of asthma among postmenopausal women from the Canadian Longitudinal Study on Aging Full Text CAN
*The Role of Curcumin in Modulating Vascular Function and Structure during Menopause: A Systematic Review Full Text
The Therapeutic Role of Genistein in Perimenopausal and Postmenopausal Women Full Text***
Reviews
Inflamm-ageing: How cytokines and nutrition shape the trajectory of ageing Full Text
Is the liver resilient to the process of ageing? Full Text
A new clinical age of aging research Full Text
Genetic and Epigenetic Alterations in Aging and Rejuvenation of Human Full Text
Longevity biotechnology: bridging AI, biomarkers, geroscience and clinical applications for healthy longevity Full Text
Senolytics/Senescent Cells
Senolytics Cocktail Dasatinib and Quercetin alleviate chondrocyte senescence and facet joint osteoarthritis in mice Full Text
A Senolytic Treatment for Liver Sepsis Full Text
Senescent cell transplantation into the skin induces age-related peripheral dysfunction and cognitive decline Full Text
Skin & Beauty
CASIN exerts anti-aging effects through RPL4 on the skin of naturally aging mice Full Text
HAPLN1 in Blood Found to Rejuvenate Skin Full Text
*The Efficacy and Safety of CollaSel Pro® Hydrolyzed Collagen Peptide Supplementation without Addons in Improving Skin Health in Adult Females Full Text
*The Effects of an Oral Supplementation of a Natural Keratin Hydrolysate on Skin Aging: A Randomized, Double-Blind, Placebo-Controlled Clinical Study in Healthy Women Full Text
*Topical Platelet Exosomes Reduce Senescence Signaling in Human Skin: An Exploratory Prospective Trial Full Text
Stem Cells
*A Bank of Centenarian Stem Cells Full Text
Rejuvenation of the reconstitution potential and reversal of myeloid bias of aged HSCs upon pH treatment Full Text
Mesenchymal Stem Cells Rejuvenate Aged Mice Full Text
Telomeres
Astragalus Supplement Lengthens Telomeres in the Middle-Aged Full Text***
Telomere stabilization by metformin mitigates the progression of atherosclerosis via the AMPK-dependent p-PGC-1α pathway Full Text
*Elevated 1-Hour Post Load Glucose as a Predictor for Telomere Attrition: a study based on a Chinese Community population Full Text
Odds & Sods
*Variety is the spice of learning, memory study suggests Full Text
*Ambient ultraviolet radiation as a cardioprotective factor: A global and regional analysis Full Text
Bats as instructive animal models for studying longevity and aging Full Text
More social species live longer, have longer generation times and longer reproductive windows Full Text
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***Disclaimer 1 – I am NOT a doctor or indeed a scientist. All the information pertained within is for information purposes only; use at your own risk. Please consult with a healthcare practitioner if you need medical advice.***
**Disclaimer 2 – In no way should supplements be a replacement for an unhealthy diet or lifestyle. A varied, plant dominant dietary pattern is the cornerstone for health. Try to eat the rainbow – the greater the variety, the greater the benefit. Even though I might take a supplement derived from a plant source, I still eat the plant in question. Also, make sure you move as much as possible – that is what we evolved to do.**
*Also bear in mind that most of the studies mentioned above are in rodents, not humans. Rodents, needless to say, do not always react the same way to drugs as humans do – witness the countless times cancer or another disease has been cured in rodents only to subsequently fail human trials. I have *starred any human trials.*
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