60 replies to this topic

[albedo]

A recent paper:

 

A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia

http://www.impactagi...ull/100926.html

 

"...Among the findings, the researchers discovered that not all muscles decline to the same extent during ageing. The leg muscles, for example, are generally affected more than those in the arm. By comparing the molecular and cellular mechanisms in these muscles in relation to their likelihood to suffer age-related decline, they established that preserving neuromuscular function (ie the communication between brain, spinal cord and muscles through nerves) protects the elderly from muscle wasting. They also demonstrated that cholesterol metabolism is impaired in the nerves that stimulate those muscles likely to suffer age-related loss of mass and strength. Discovering a way to reverse that process could help prevent such physical decline..." (bold mine)

https://www.nestlein...ting-in-old-age

[albedo]

A fascinating result from EPFL on the beneficial effect of pomegranate spot by Normalizing here. I thought useful to report it also here for those following this thread:

 

Gut bacteria unleash anti-aging power of pomegranates

http://www.medicalne...cles/311572.php

 

See the press release: "Breakthrough findings on urolithin A, a pomegranate metabolite, on muscle aging, published in Nature Medicine; Amazentis announces first human clinical trial"

http://info325914.wix.com/amazentis

 

 

 

 

[corb]

A fascinating result from EPFL on the beneficial effect of pomegranate spot by Normalizing here. I thought useful to report it also here for those following this thread:

 

Gut bacteria unleash anti-aging power of pomegranates

http://www.medicalne...cles/311572.php

 

See the press release: "Breakthrough findings on urolithin A, a pomegranate metabolite, on muscle aging, published in Nature Medicine; Amazentis announces first human clinical trial"

http://info325914.wix.com/amazentis

 

 

 

Urolithin A is the only molecule that can relaunch mitophagy

That's quite the statement they have right there. Wasn't NMN hyped for the same thing, ehhhh what? Not even two years ago, right?
It's a good thing anti-aging makes the headlines though. At least people are becoming more open to the idea.

[albedo]

A review article on nutrition's impact, cherry picking some points I found interesting, in particular the earlier interventions in life:

 

Nutrition and Sarcopenia: A Review of the Evidence and Implications for Preventive Strategies

http://www.hindawi.c...012/510801/abs/

 

"...The nutrients that have been most consistently linked to sarcopenia and frailty in older adults are vitamin D, protein, and a number of antioxidant nutrients, that include carotenoids, selenium, and vitamins E and C [10]. However, there is also some evidence that variations in long-chain polyunsaturated fatty acid status may have important effects on muscle strength in older people [13]..."

 

"...Intervention studies that take a food-based or “whole diet” approach are likely to change intakes of a range of nutrients and, therefore, have the potential to be more effective than single nutrient supplementation studies in preventing age-related losses in muscle mass and strength..."

 

"...whilst consumption of a high proteinmeal has been shown to increase muscle protein synthesis in older adults by ∼50%, combining a high protein meal with resistance
exercise increases synthesis more than 100% [39]..."

 

"...However, muscle mass and strength achieved in later life are not only determined by the rate of muscle loss, but also reflect the peak attained earlier in life, and efforts to prevent sarcopenia also need to recognise the potential effectiveness of interventions earlier in the lifecourse..."

[albedo]

A new evidence on resveratrol:

 

Resveratrol primes the effects of physical activity in old mice

http://journals.camb...ne&aid=10458324

 

"Decrease in muscle mass and performance with ageing is one of the main factors of frailty in the elderly. Maintenance of muscle performance by involving in physical activities is essential to increase independence and quality of life among elderly. The use of natural compounds with ergogenic activity in old people would increase the effect of moderate exercises in the maintenance of physiological muscle capacity. Resveratrol (RSV), a polyphenol found in walnuts, berries and grapes, shows this ergogenic activity. By using young, mature and old mice as models, we have found that RSV improves muscle performance in mature and old animals but not in young animals. Without showing significant effect by itself, RSV primed the effect of exercise by increasing endurance, coordination and strength in old animals. This effect was accompanied by a higher protection against oxidative damage and an increase in mitochondrial mass. RSV increased catalase and superoxide dismutase protein levels in muscle and primed exercise to reverse the decrease in their activities during ageing. Furthermore, RSV increased the level of mitochondrial mass markers such as cytochrome C, mitochondrial transcription factor A and nuclear respiratory factor-1 in muscle in exercised animals. Our results indicate that RSV can be considered an ergogenic compound that helps maintain muscle performance during ageing and subsequently reduces frailty and increases muscle performance in old individuals practising moderate exercise."

[albedo]

An interesting article focusing on the mitochondrial dysfunction which is one of the key hallmarks of aging:

 

The ageing neuromuscular system and sarcopenia: a mitochondrial perspective

 

 sarcopenia.png   55.5KB   1 downloads

 

"Skeletal muscles undergo structural and functional decline with ageing, culminating in sarcopenia. The underlying neuromuscular mechanisms have been the subject of intense investigation, revealing mitochondrial abnormalities as potential culprits within both nerve and muscle cells. Implicated mechanisms involve impaired mitochondrial dynamics, reduced organelle biogenesis and quality control via mitophagy, accumulation of mitochondrial DNA (mtDNA) damage and respiratory chain defect, metabolic disturbance, pro-apoptotic signalling, and oxidative stress. This article provides an overview of the cellular mechanisms whereby mitochondria may promote maladaptive changes within motor neurons, the neuromuscular junction (NMJ) and muscle fibres. Lifelong physical activity, which promotes mitochondrial health across tissues, is emerging as an effective countermeasure for sarcopenia."

 

http://onlinelibrary...271212/abstract

 

It goes well along with the role of Urolithin A and mitophagy.

[Harkijn]

I came across this recent (Sept. 2015) study. Indeed it is strange tomatidine is not discussed more. Reputable companies such as the Life Extension Foundation should research on this but maybe the cost prohibitiveness you mention is discouraging so far? LEF is normally quite innovative and fast to market when they found there is one and safety profile is good. They fund research and I just wonder if you ever tried to look for a research grant with them. Considering the condition the product could be very interesting!

 

Identification and Small Molecule Inhibition of an ATF4-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy

 

Abstract

Aging reduces skeletal muscle mass and strength, but the underlying molecular mechanisms remain elusive. Here, we used mouse models to investigate molecular mechanisms of age-related skeletal muscle weakness and atrophy, as well as new potential interventions for these conditions. We identified two small molecules that significantly reduce age-related deficits in skeletal muscle strength, quality and mass: ursolic acid (a pentacyclic triterpenoid found in apples) and tomatidine (a steroidal alkaloid derived from green tomatoes). Because small molecule inhibitors can sometimes provide mechanistic insight into disease processes, we used ursolic acid and tomatidine to investigate the pathogenesis of age-related muscle weakness and atrophy. We found that ursolic acid and tomatidine generate hundreds of small positive and negative changes in mRNA levels in aged skeletal muscle, and the mRNA expression signatures of the two compounds are remarkably similar. Interestingly, a subset of the mRNAs are repressed by ursolic acid and tomatidine in aged muscle are positively regulated by the transcription factor ATF4. Based on this finding, we investigated ATF4 as a potential mediator of age-related muscle weakness and atrophy. We found that a targeted reduction in skeletal muscle ATF4 expression reduces age-related deficits in skeletal muscle strength, quality and mass, similar to ursolic acid and tomatidine. These results elucidate ATF4 as a critical mediator of age-related muscle weakness and atrophy. In addition, these results identify ursolic acid and tomatidine as potential agents and/or lead compounds for reducing ATF4 activity, weakness, and atrophy in aged skeletal muscle.

 

http://www.jbc.org/c...681445.abstract

The Dutch Language 'sister' website  to Ergo-log.com mentions that tomatidine will soon be available via a company called Antaeus Lab. No price indication available yet.

[albedo]

A fascinating result from EPFL on the beneficial effect of pomegranate spot by Normalizing here. I thought useful to report it also here for those following this thread:

 

Gut bacteria unleash anti-aging power of pomegranates

http://www.medicalne...cles/311572.php

 

See the press release: "Breakthrough findings on urolithin A, a pomegranate metabolite, on muscle aging, published in Nature Medicine; Amazentis announces first human clinical trial"

http://info325914.wix.com/amazentis

 

Just wish to link to a parallel discussion going on a different thread dedicated to the EPFL's results.

 

[albedo]

A fascinating result from EPFL on the beneficial effect of pomegranate spot by Normalizing here. I thought useful to report it also here for those following this thread:

 

Gut bacteria unleash anti-aging power of pomegranates

http://www.medicalne...cles/311572.php

 

See the press release: "Breakthrough findings on urolithin A, a pomegranate metabolite, on muscle aging, published in Nature Medicine; Amazentis announces first human clinical trial"

http://info325914.wix.com/amazentis

 

The preliminary results on the human clinical presented at the Bacelona conference today (ICFSR 2017, http://www.frailty-sarcopenia.com/) look encouraging. I will follow when data will be published.

 

 Urolithin A results April 28 2017.PNG   288.56KB   1 downloads

 

Here is a journalistic report (in French):

 

Une molécule anti-vieillissement de la grenade testée chez l'homme avec succès

https://www.sciences...c-succes_112494

 

(edit: add picture)

Edited by albedo, 28 April 2017 - 03:42 PM.

[alc]

"Amazentis SA Announces Successful Phase 1A/1B Study Results in Healthy Elderly Subjects with the Food Metabolite Urolithin A"

 

http://pdf.amazentis...27April2017.pdf

[venusshek]

I saw a good thread about it on isarms, sadly i'm not allowed to post links

[Rocket]

Ginkgo Biloba

http://www.google.co...kZ9vvKzgLt9Xr2A

Also, I would think that creatine might be helpful.

I agree that hitting the weights is the best natural way to prevent muscle loss.

You are aware that as age progresses that the kidneys slowly fail..... Just coincidentally as you age and experience sarcopenia. And your solution is to add creatine into someone with failing kidneys??? LOL

[Rocket]

The best treatment is a little testosterone and protein and weight training. For women, perhaps anavar in place of testosterone.

But its my understanding that a sizable portion of sarcopenia is caused by leaking calcium channels. Thats why guys like Arnie who are 70 and still huge from training can't lift whet they used to lift in their 50s.

Can someone who isn't an internet trained doctor (know it all) comment on the leaky calcium channels?

Edited by Rocket, 13 May 2017 - 02:17 AM.

[albedo]

 

I came across ...

The Dutch Language 'sister' website  to Ergo-log.com mentions that tomatidine will soon be available via a company called Antaeus Lab. No price indication available yet.

 

 

http://www.ergo-log....solic-acid.html
 

[albedo]

A fascinating result from EPFL on the beneficial effect of pomegranate spot by Normalizing here. I thought useful to report it also here for those following this thread:

 

Gut bacteria unleash anti-aging power of pomegranates

http://www.medicalne...cles/311572.php

 

See the press release: "Breakthrough findings on urolithin A, a pomegranate metabolite, on muscle aging, published in Nature Medicine; Amazentis announces first human clinical trial"

http://info325914.wix.com/amazentis

 

Update news: AMAZENTIS got additional funding (~8m$) for two clinical trials on their pomegranate supplement. The first (Kevin Conley, UoW) will look at healthy people 65 yo and older with initiating muscular fraily and the second (Canada) will look at endurance increase by Urolithin A of people 45-65 yo with obesity.

 

Bioenergetics and Muscle Function Improvement With AMAZ-02 in Elderly Skeletal Muscle (ENERGIZE Trial)

https://clinicaltria...how/NCT03283462

 

AMAZ-02 Effect on Exercise ToLerance in Healthy, Overweight Middle Aged Subjects (ATLAS Trial) (ATLAS)

https://clinicaltria...how/NCT03464500

[pleb]

I've actually put on muscle slowly without any exercise using RAD 140 , it's a SARM that mimics both testosterone and steroids, it's not expensive and has almost no side affects small enough that they are not noticed, but don't take the amounts mentioned online 12 mg is the maximum I only take 8mg and still built muscle slowly, do your own search online about it and compare prices, it's even available on ebay or amazon,

[albedo]

Strange this has not been discussed more on LC: the peptide apelin plays a key role in muscle aging and sarcopenia. See also reason's post here.

 

I wonder (i) how you can measure it and if there are proxys you can readily access in our blood tests and (ii) which is, next to exercise, the strategy to increase its levels?

 

(edid: add reason's link)

Edited by albedo, 22 September 2018 - 10:43 AM.

[Rocket]

ive read about mk-677 before. if i recall correctly, it is sort of like a designer version of HGH, but it doesn't illicit an insulin response. part of the problem w/ HGH is that people become diabetic while using it for an extended period of time, and MK-677 doesn't have that drawback.

the best way to deal w/ sarcopenia today really is a bit of whey protein and hitting the weights. it'd be nice if everything were solvable by pills, but it seems unlikely at this point.

The insulin effects of HGH are countered by taking dhea. Teenagers have high HGH and aren't diabetic because they also have high dhea.

Whey protein and lifting doesn't solve sarcopenia. Its just counteracts the effects of sitting on your butt and doing nothing but wasting away.

[albedo]

http://www.ergo-log....solic-acid.html
 

 

Nestlé Health Science invests in global strategic partnership with Amazentis to develop its new cellular nutrient Urolithin A

 

https://www.prnewswi...-300822293.html

 

[albedo]

This seems to me very important and promising also from the genetic therapy perspective. From Auwerx's team:

 

The exercise-induced long noncoding RNA CYTOR promotes fast-twitch myogenesis in aging

 

https://www.science....anslmed.abc7367

[albedo]

Emphasizing better screening tools:

 

"The SARC-F had good reliability, low to moderate sensitivity, and
moderate to high specificity in identifying sarcopenia, independent of
the sarcopenia definition. The SARC-CalF had higher sensitivity
compared with the SARC-F. Despite the good reliability of the SARC-F,
its low to moderate sensitivity makes it nonoptimal to use the tool to
screen for sarcopenia in older adults. Additionally, the SARC-F and the
SARC-CalF were not shown to perform better in certain populations.
As such, it is recommended to apply the diagnostic criteria for sar-
copenia without screening"

 

"This stresses the need for a screening tool that has a better AUC and
Youden Index. Creating a new screening tool that includes de-
terminants of sarcopenia could be considered"

 

https://www.jamda.co...0475-8/fulltext

[Woody42]

Here is an interesting article about protein distrubution. Yes it's mostly animal studies but about 1/2 way

through it does talk about a human study using wemen about 60 years old. It showed that the higher the

% of there daily protein intake eaten  at breakfast the more muscle mass they gained.   https://www.scienced...007129?via=ihub

 

[johnhemming]

I see sarcopenia as a number of issues

a) Exercise

b) Nutrition

c) The extent to which satellite cells differentiate properly and produce the right proteins.#

 

My own n=1 experiments have involved trying to do chin-ups (I am 62 and have not previously in my life tried to do this).  When I started about March/April I needed latex straps to hold some of my weight, but can now do a small number in sequence without assistance.  Hence I think solving c) is the key, but without a and b you won't maintain or build muscle.

[albedo]

I see sarcopenia as a number of issues

a) Exercise

b) Nutrition

c) The extent to which satellite cells differentiate properly and produce the right proteins.#

 

My own n=1 experiments have involved trying to do chin-ups (I am 62 and have not previously in my life tried to do this).  When I started about March/April I needed latex straps to hold some of my weight, but can now do a small number in sequence without assistance.  Hence I think solving c) is the key, but without a and b you won't maintain or build muscle.

 

You might wish to follow the work of Prof Robin Daly (*). E.g. https://pubmed.ncbi..../#affiliation-1. I recollect a presentation of his basically emphasizing some of the aspects of your post.

 

(*)

Professor Robin M. Daly, Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway, Burwood, Melbourne, Victoria, Australia 3125, Phone: +61 3 9244 6040, Email: rmdaly@deakin.edu.au, ORCID ID: 0000-0002-9897-1598.
 

[johnhemming]

You might wish to follow the work of Prof Robin Daly (*). E.g. https://pubmed.ncbi..../#affiliation-1. I recollect a presentation of his basically emphasizing some of the aspects of your post.

 

  None of it is that surprising.  If you don't have the right building blocks (particularly protein) you cannot build muscle.  You also need to do the exercise to stimulate HIF 1 alpha.  Also the cells need to create the right proteins.  (which is confirmed in various papers).

[albedo]

You might wish to follow the work of Prof Robin Daly (*). E.g. https://pubmed.ncbi..../#affiliation-1. I recollect a presentation of his basically emphasizing some of the aspects of your post.

 

(*)

Professor Robin M. Daly, Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway, Burwood, Melbourne, Victoria, Australia 3125, Phone: +61 3 9244 6040, Email: rmdaly@deakin.edu.au, ORCID ID: 0000-0002-9897-1598.
 

 

https://bit.ly/3P8cWkN
 

[Lady4T]

I've actually put on muscle slowly without any exercise using RAD 140 , it's a SARM that mimics both testosterone and steroids, it's not expensive and has almost no side affects small enough that they are not noticed, but don't take the amounts mentioned online 12 mg is the maximum I only take 8mg and still built muscle slowly, do your own search online about it and compare prices, it's even available on ebay or amazon,

 

I've always been one of those "too thin" people who's basically unable to put on weight. All my adult life it's been a struggle just to maintain. But I'm getting older and losing muscle. Sarcopenia, cachexia, whatever name you want to give it... I need my skeletal muscle back!  So I'm ready to try some RAD-140.

[albedo]

Sorry .. pay-walled! Also dated past year. Must be a good read though.

 

Dent E, Woo J, Scott D, Hoogendijk EO. Sarcopenia measurement in research and clinical practice. European Journal of Internal Medicine. 2021;90:1-9.

 

• •
  Sarcopenia is an age-related loss of muscle mass associated with decreased function.
• •
  Sarcopenia has no gold standard diagnostic tool.
• •
  Diagnostic criteria include muscle mass, strength and physical performance.
• •
  Muscle mass is becoming less central as a diagnostic criterion
• •
  The most common tool is that of the European Working Group for Sarcopenia (EWGSOP).

Abstract

Sarcopenia is a disease related to accelerated loss of skeletal muscle and subsequent decline in functional capacity. It affects approximately 13% of the world's population aged over 60 years. Sarcopenia is primarily managed and prevented through a combination of exercise prescription combined with appropriate nutritional strategies. This review outlines diagnostic and case finding/screening tools for age-related (primary) sarcopenia used in research and clinical practice. Diagnostic tools critically reviewed include those of the: European Workgroup for Sarcopenia (EWGSOP) versions 1 and 2; Asian Working Group for Sarcopenia (AWGS) versions 1 and 2; Foundation for the National Institutes of Health (FNIH); and the Sarcopenia Definition and Outcomes Consortium (SDOC). Criteria used by diagnostic tools (muscle mass, muscle strength and physical functioning/performance) are also detailed. Case-finding tools include the SARC-F questionnaire, Ishii's formula and Goodman's screening grid. Additionally, this review discusses the strengths and weaknesses of each diagnostic and case-finding tool, and examines their ability to reliably predict adverse clinical outcomes and patient responses to potential therapies.

 

[Woody42]

I have seen a couple of articles like this one saying getting a higher percentage of your daily protein early in the day

helps preserve lean body mass  much better than having it later in the day.  https://pubmed.ncbi....h.gov/23915061/

 

 

[Lady4T]

I have seen a couple of articles like this one saying getting a higher percentage of your daily protein early in the day

helps preserve lean body mass  much better than having it later in the day.  https://pubmed.ncbi....h.gov/23915061/

 

"Conclusions: In this sample of healthy older persons, amount of protein intake was not associated with frailty, but distribution of protein intake was significantly different between frail, pre-frail and non-frail participants. More clinical studies are needed to further clarify the relation between protein intake and frailty."

 

Thanks, Woody, for posting this. I was not aware of this information, and it makes sense to me. I have now adjusted my protein intake to intake most of it in my morning meal. I hope it makes a difference.