2020 Longevity Year in Review

Despite the year we’ve had, it is always a pleasure to take a step back and look at how far the longevity field has come, for we have come a long way in understanding and being able to treat ageing. 2020 was no exception. From breakthroughs in cellular reprogramming to human trials in blood plasma fractions, the longevity field continues to accelerate.

At the beginning of COVID I worried as to how much it would impact longevity research, however the output of scientific papers did not seem to diminish. Having said that, research takes a long time from initial discovery to final published study, so there could still be a bit of a hangover in the years ahead.

In this end of year review, I have chosen not to compile a top ten list or anything. Instead, I have written a narrative review based on a few broader headings, providing links to the most important and interesting studies - likewise with the supplemental section, though I have kept the same list of supplements & lifestyle factors. For any new readers, I should note that the list of supplements is not exhaustive and merely reflects what I have started taking myself based on previous research. I believe that a lot of natural supplements are redundant since they seem to affect the same genetic signaling pathways.

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Just like the rest of the world, COVID derailed most of the plans I had for 2020, however there were still a few highlights. In February I spoke with my local MP again, who reiterated his support, and also joined Meetup.com, managing to have the first meeting of the Toronto Longevity Association before COVID struck. Throughout the year I continued to volunteer for the Life Extension Advocacy Foundation (LEAF), providing them with longevity leads for their news site and monthly Rejuvenation Roundup. I also helped again with their (virtual) conference Ending Age Related Diseases in August.

Moving forward, in 2021 I intend to launch a registered non-profit advocating for increased funding for longevity research in Canada, and which would also foster collaboration among Canadian (& international!) longevity researchers, since we don’t seem to be as well-funded or organised as in the US. Help in this endeavour is most welcome!

Wishing you all a much better 2021!

You can follow me on Twitter @ChrisPollyanna1 for the latest updates.

You can also join the Toronto Longevity Association Facebook group.

Lastly, due to a suggestion from a kind & generous reader in the past week, I’ve set up a Patreon account. Although I write this newsletter out of love and never sought monetary reward for it, if it is of use to you and you wish to show your support, then my appreciation would be beyond words!

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For an alternative, broader and much more detailed review of 2020, check out Reason from Fight Aging!’s take: A Look Back at 2020: Progress Towards the Treatment of Aging as a Medical Condition

And here is a video look back from LEAF: Lifespan News – Looking Back at 2020

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Senescent Cells / Senolytics

Despite the setback of the failed Unity Biotechnology trial for Osteoarthritis, strong progress continued to be made, especially in broadening the attack on senescent cells (SC) with many new avenues being opened up. First up was a way to increase the selectivity of SC clearance through the use of a prodrug. However, in terms of selectivity, nothing beats our immune system and one group of researchers have developed a vaccine to prevent the accumulation of senescent T-cells. Another group has harnessed the power of CAR T cells, used with such effect against blood cancers, to eliminate SCs. Finally, instead of eliminating the SCs, other researchers have managed to revert them back to a normal non-damaging state.

Elsewhere, work has continued on existing senolytic drugs, several of which are now in human trials, such as Dasatinib/Quercetin and Fisetin. For an overview of the myriad of companies working in this field and the diversity of their approaches, check out this great Nature article.

Cellular Reprogramming

The area I’m most excited about involves reprogramming cells back to a youthful state, the power of which was demonstrated when cells from a 114 year old were successfully rejuvenated. Another, even more powerful, demonstration came in a living animal whereby making its cells young again resulted in returned sight. Similarly, there were striking results for Parkinson’s Disease symptoms and improving mouse memory. It is still going to be some before this moves into humans, but there is palpable excitement within the community as to where this could lead.

Blood Factors

There is little doubt that there are factors in the blood which either keep us young, or make us old (and it’s probably a combination of the two in my opinion). Validation for either side kept on coming with an interesting pre-print suggesting that young plasma could cut the epigenetic age of old rats in half. On the other side, two papers showed that simply diluting old plasma can also have a rejuvenatory effect, including the improvement of cognition.

Unlike cellular reprogramming, both of these approaches are much closer to becoming available for us. Indeed, phase 2 clinical trials have already taken place for the addition of plasma, while Russian biohackers have tried diluting their own plasma, which will be the subject of an official clinical trial this year. A summary of some of the positive and negative blood factors can be found here.

Stem Cells, Exosomes and other Transplants

It used to be thought that the benefit of stem cells came from replacing dysfunctional cells, but it turns out that it is primarily the substances they secrete, such as exosomes, which provide that benefit. But, it also depends on the age of the source material, as stem cells from older animals given to other old animals cause more harm. When taken from younger animals or human umbilical cords, stem cells could extend lifespan by 12%, as well as protect the thymus and liver from NASH. Similarly, frailty was reduced if a type of immune cell was transplanted. When just the exosomes were used, they could improve spinal cord injuries and certain senescent markers. Additionally, they can be used to rejuvenate older stem cells and improve their ability to repair the heart.

Ageing Clocks

Throughout 2020 it seemed like hardly a week went by without a new ageing clock being released. These included clocks for mice, naked mole-rats, plasma, proteomics, RNA, the microbiome and even psychology! Others, such as for Deep Learning, claimed to be the most accurate yet. However, the most important studies compared existing clocks to see which were the most accurate at predicting mortality, including cancer, which turned out to be GrimAge in a couple of studies. Truly accurate ageing clocks will speed up longevity research, as it will take less time to see if the intervention is working in humans.

Life Extending Studies

As ever, there was a plethora of life extending interventions in model organisms (usually worms), mostly involving the same genetic pathways such as NRF2 or mTOR and being fairly minor in effect. I’ve chosen just a few to highlight, picking those that are already in human use: Alpha-Ketoglutarate, Canagliflozin, Carnitine & Verapamil. A couple also showed indications of reduced human mortality: Glucosamine and Pioglitazone.

Other Areas: Thymus Rejuvenation, Microbiome, Telomeres & Gene Therapy

There were a couple different attempts at rejuvenating the thymus, using FOXN1-reprogrammed embryonic fibroblasts and natural whole-organ scaffolds. A rejuvenated thymus would at least partially rejuvenate our immune system. This research also has positive implications for other, larger organs.

Studies on the impact of the microbiome continued, showing the potential effects of the Mediterranean diet, how a leaky gut could be prevented, how the microbiota from long lived people reduces age-related indices, and how probiotics could improve cognition in humans.

I’ve grown increasingly disillusioned with the predictive powers or utility of telomeres, however, I remain open minded and there were still a few interesting studies showing that telomerase gene therapy prevented mouse lung fibrosis, that telomere length could predict facial ageing and that telomere length could be increased through exercise or lifestyle intervention.

Finally, it’s also worth mentioning a couple instances of gene therapy to treat muscle wasting, one of which used CRISPR.

Supplemental Section

Fasting/Dietary Restriction

The reduction of daily calorie intake has long been known to be beneficial, however evidence is increasingly coming out that intermittent fasting (IF) in all its myriad of flavours can have similar benefits. First off, more data has come through regarding calorie restriction. Even though participants only reduced their food intake by 12%, their weight and liver biomarkers improved. For IF, it improved cognition and weight loss, with Ramadan fasting also showing an anti-cancer proteomic signature. The form of IF I practice, Time Restricted Feeding (only eating in an 8 - 10 hour window each day) was shown to be practical, even for older people, and resulted in improved insulin sensitivity in the young.

Diet

As it has become abundantly clear, the Mediterranean diet, or variations thereof, is the healthiest diet. Further evidence came out in 2020 showing preserved white matter integrity, reduced risk of hepatic steatosis and improved blood vessel function in patients with coronary heart disease. It also altered the microbiome and reduced frailty and most impressively promoted epigenetic rejuvenation. It has been proposed that a Pesco-Mediterranean diet with intermittent fasting could be healthiest of all.

Moving to individual foods, nuts can reduce cancer risk, while walnuts, blueberries and cocoa can improve cognition. Cocoa can also improve Peripheral Artery Disease, while spices in general can improve inflammation after a fatty meal. In terms of drinks, tea reduces mortality (backed up by a study in rats), but even better is a combination of both tea and coffee. Finally, a ketogenic drink improved cognition in mild cognitive impairment.

Exercise

All and any form of exercise is beneficial, but evidence is increasingly emerging for the importance of resistance exercise for the health of the elderly, as it not only maintains muscle mass, but also prevents cellular ageing and raises NAD+ levels. However, aerobic exercise should not be discounted as it can improve cognition, sexual function and vascular age if you train for a marathon. But, even walking an extra 1,000 steps a day reduces mortality by >6%. If you want the biggest bang for your buck though, high intensity interval training (HIIT) is the way to go as a mere 60 seconds worth a week provides significant benefits!

Non-Prescription Supplements (in alphabetical order)

Astaxanthin

The most powerful carotenoid, Astaxanthin improved the self reported physical activity level and quality of life for cardiac patients and improved cardiac contractility and exercise tolerance for those with Left Ventricular Heart Failure. For the healthy, it improved performance in a 40km cycling time trial, while a systematic review found it raised HDL-C while lowering CRP. In animal models it also protected against skin sun-ageing and various eye diseases.

Curcumin

The spice which gives curries their yellow colour, Curcumin showed positive effect in a number of diseases such as Crohn’s, Ulcerative Colitis, NASH and liver cirrhosis, as well as mood and working memory. There were also a number of studies showing that it improves post-exercise muscle soreness and glycemic & lipidemic status.

Fisetin

No human studies, but in animal models Fisetin was protective for the heart, Parkinson's Disease and fibrosis of the liver and lung, as well as proventing sepsis induced organ dysfunction. There was also a novel derivative, CMS121, which prevented memory decline.

Melatonin

Although used primarily as a sleep aid, Melatonin can also reduce oxidative stress in humans. In animal models, Melatonin was shown to prevent hearing loss, improve mitochondrial biogenesis, inhibit vascular smooth muscle cell proliferation, protect oocytes during maturation and facilitate long‐term object memory.

Nicotinamide MonoNucleotide (NMN)

In animal models, two separate studies showed that NMN reverses declining fertility. It also can rejuvenate mitochondria, promote neurovascular rejuvenation, and prevent liver fibrosis, osteoporosis, photoreceptor degeneration and diabetes-induced cognitive impairment.

Nicotinamide Riboside (NR)

NR, which has been studied longer than NMN, was shown in humans to suppresses inflammatory activation of PBMCs in heart failure, while two primarily safety studies showed increased skeletal muscle acetylcarnitine concentrations and increased NAD+ levels in combination with Pterostilbene in Acute Kidney Injury. Meanwhile in animals, it also prevented hearing loss in Cockayne syndrome.

Pterostilbene

One human trial of Pterostilbene in conjunction with NR showed increased NAD+ levels in Acute Kidney Injury, while in animal models it reduced colonic inflammation, protected cochlea from ototoxicity, prevented renal & pulmonary fibrosis, and enhanced endurance capacity.

Resveratrol

A number of human trials of Resveratrol came out in 2020, including where it improved motor function in patients with muscular dystrophies. In postmenopausal women, long term supplementation improved cognition, cardio-metabolic markers, bone mineral density and overall well-being. It also improved flow-mediated dilation in coronary artery disease patients, diabetic markers, sperm motility and skeletal muscle mitochondrial function when combined with exercise.

Spermidine

In humans, Spermidine improved cognition in dementia patients, was associated with cortical thickness and hippocampal volume, modulated T-cell function & autophagy levels, and improved vascular endothelial function. In animals, it delayed brain aging, reduced pulmonary fibrosis, and improved gut barrier integrity and healthspan.

Prescription Supplements

Metformin

There were doubtless a ton of studies on Metformin with regards to its initial indication for diabetes, but in other studies its use was associated with slowed cognitive decline and reduced risk of osteoporosis, as well as beneficial effects on aging-associated pathways in muscles. In animals it rescued rapamycin-induced mitochondrial dysfunction and reduced rheumatoid arthritis with metabolic syndrome.

Rapamycin (sirolimus)

In humans, Rapamycin prolonged the antidepressant treatment effects of ketamine and increased response & remission rates. In animals, a follow up study to the initial ITP lifespan study showed that short term or intermittent treatment also increased lifespan, especially in males. In other studies, it rejuvenated oral health, improved osteoarthritis, inhibited a form of cell death, reduced Ischemia/Reperfusion Injury in the brain and heart, and in the eye it reduced inflammation and glaucomic eye pressure. And finally, a couple reviews of its signaling pathway and effect of aging and age-related diseases.

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