Are you feeling prematurely old?

A

Barts-MS rose-tinted-odometer: ★★ (Gray Thursday as in getting old Thursday #808080)

As you are all aware ageing is a fact of life and is essential for evolution to do its job properly. Even bacteria and fungi age. Ageing is, therefore, a biological process and is driven by various biological pathways and networks controlled by our genes. It is well known that chronic inflammation results in accelerated ageing and there is a hypothesis that multiple sclerosis (MS) causes premature ageing and is one of the drivers of smouldering or non-relapsing progressive MS. 

One of the biological markers of ageing is the length of your chromosomes. As cells divide, the end of the chromosomes or telomeres shorten. The length of the telomeres can be used as a biological clock of ageing. The review below of 7 studies in pwMS shows that pwMS have shorter telomeres than controls; in other words, they are biologically older than healthy age-matched controls. 

Shorter telomeres, i.e. premature ageing, in pwMS is associated, independently of age, with greater disability, lower brain volume (end-organ damage), increased relapse rate and more rapid conversion from relapsing to progressive MS. 

So is there anything you can do about the ageing process? Yes, make sure you are NEIDA (no evident inflammatory disease activity) and that you are doing everything you can from a health and wellness perspective, which are the only antiageing strategies at our disposal. 

I am seeing an increasing number of older people with MS, i.e. 50+ years of age, who are developing progressive worsening of their functioning after many years of being NEIDA on a DMT and stable physically. When I interrogate these patients clinically, radiologically with MRI and biochemically (spinal fluid analysis) I can’t find any evidence of MS disease activity. I simply say these people have smouldering MS, but I suspect a large part of what we are seeing is age-related neurodegeneration that is occurring decades early than it should because MS has shredded their brain and cognitive reserve. The only solution to this problem is early diagnosis and treatment upfront with the aim of protecting the reserve capacity of the nervous system so pwMS can age normally. The latter is why we launched our “MS Brain Health: Time Matters” initiative to address this problem. 

Please let me know what you are doing to protect your brain and cognitive reserve? Do you feel prematurely old? What advice do you have for the next generation of pwMS? 

Bühring et al. Systematic Review of Studies on Telomere Length in Patients with Multiple Sclerosis. Aging Dis. 2021 Aug 1;12(5):1272-1286.

Telomeres are protective cap structures at the end of chromosomes that are essential for maintaining genomic stability. Accelerated telomere shortening is related to premature cellular senescence. Shortened telomere lengths (TL) have been implicated in the pathogenesis of various chronic immune-mediated and neurological diseases. We aimed to systematically review the current literature on the association of TL as a measure of biological age and multiple sclerosis (MS). A comprehensive literature search was conducted to identify original studies that presented data on TL in samples from persons with MS. Quantitative and qualitative information was extracted from the articles to summarize and compare the studies. A total of 51 articles were screened, and 7 of them were included in this review. In 6 studies, average TL were analyzed in peripheral blood cells, whereas in one study, bone marrow-derived cells were used. Four of the studies reported significantly shorter leukocyte TL in at least one MS subtype in comparison to healthy controls (p=0.003 in meta-analysis). Shorter telomeres in patients with MS were found to be associated, independently of age, with greater disability, lower brain volume, increased relapse rate and more rapid conversion from relapsing to progressive MS. However, it remains unclear how telomere attrition in MS may be linked to oxidative stress, inflammation and age-related disease processes. Despite few studies in this field, there is substantial evidence on the association of TL and MS. Variability in TL appears to reflect heterogeneity in clinical presentation and course. Further investigations in large and well-characterized cohorts are warranted. More detailed studies on TL of individual chromosomes in specific cell types may help to gain new insights into the 

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice. 

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

25 comments

  • I feel prematurely old, I am 48 and shrinking in height I’ve lost about an inch this year and am down to 5ft 1—-I know we sometimes shrink as we get older, but before 50??

    less movement because of lockdown and still shielding? the Ocrevus?

  • Exercise; lots of exercise. Walk if you can’t run. Paddle if you can’t swim, Lift dumbbells from a wheelchair if you can’t stand. Use therabands if you can’t sit up. Dance can be incredible demanding like ballet or very achievable if it’s just moving to music.
    Plenty of water. No junk food. Don’t smoke. Drink little or no alcohol. It doesn’t mean a miserable existence by the way. I do occasionally have a drink but never too much. If you hate exercise then, you may not be able to maintain your EDSS but if you can, give it a try. It’s the most neuroprotective thing you can do.

    • “If you hate exercise then, you may not be able to maintain your EDSS”

      Please stop…not true…if exercise stops progression than Lou Gehrig would have been able to
      keep playing baseball…he did tons of exercise. Exercise does alter disease process/pathology.

      “He set several major-league records during his career, including the most career grand slams (23) (since broken by Alex Rodriguez) and most consecutive games played (2,130), a record that stood for 56 years and was long considered unbreakable until surpassed by Cal Ripken Jr., in 1995.
      Batting average: .340
      Runs batted in: 1,995
      Home runs: 493

      “It’s the most neuroprotective thing you can do.”

      No…HSCT is the most neuroprotective thing you can do.

      • Ideally one would get Lemtrada or HSCT and also do tons of exercise. I don’t think anyone should assume that even HSCT has fully eliminated the disease. Do everything you can to give yourself the best chance. I agree that exercise won’t do very much if you don’t also get a highly effective treatment (meaning better than Ocrevus).

  • “I am seeing an increasing number of older people with MS, i.e. 50+ years of age, who are developing progressive worsening of their functioning after many years of being NEIDA on a DMT and stable physically. When I interrogate these patients clinically, radiologically with MRI and biochemically (spinal fluid analysis) I can’t find any evidence of MS disease activity.”

    I find these posts hope sapping. A patient unlucky enough to get MS takes all the advice – induction therapy early on, exercise, diet, other brain health measures, yet their destiny (worsening function) can’t really be changed! What happened to the treatment pyramid (apart from anti-inflammatories)? Where are we with remyelination and reparative therapies? Will trials such as Sizomus have any impact on progressive worsening if the worsening is caused by premature ageing? My take home message is that MS is an insidious disease and comes up with another nasty surprise, despite all the efforts of the patient. I’d advise MS patients eg over 50, to take your pension (work pension) early ie retire early. It’s pretty clear from the post above that most MSers won’t get the active and full retirement in their 60s and 70s (which I regard as ‘older people” not 50) which they planned for. A friend with MS is 56 (and was on highly effective treatments) and just about manages to operate her electric wheelchair with one finger. Looks like there’s a lot more to do to really tackle this disease and really change patients lives for the long term.

    • I just want to point out that if your friend is 56, the earliest she would have been able to start highly effective treatment on the NHS is 2005 (with natalizumab), so at 40. That’s already quite a lot of time with under or untreated MS if she had onset at a typical age somewhere between 20 and 30. And it would have taken even longer to start natalizumab if she had been put through a typical escalation approach.

      I hope that those of us who are diagnosed early and get highly effective treatment right away can get expect a better disease course.

      • She was on injectables before getting Tysabri in the mid 2000s. She was waking with a cane until c.2012. Her progression has been very quick which has shocked me to the core. When she was diagnosed in the mid 1990s she was told her course was likely to be mild as she was a woman and her relapses were sensory! I like you hope the use of highly effective therapies early on will improve long term outcomes. However, the concept of smouldering MS and ageing as a driver of neuro-degeneration shows there’s more work to do.

      • “I hope that those of us who are diagnosed early and get highly effective treatment right away can get expect a better disease course.”

        Define “highly effective” Rituximab/Ocrevus..Tysabri..Copaxone..Betaseron
        ….none of those will prevent spms or get one to normal brain atrophy.

  • I felt prematurely old when on Copaxone, my hair turned white and I hurt all over, when I ditched it I got the pigment back and the pain stopped (among other things).
    A family member died in his teens, I am in my 50’s, I don’t waste time fretting over aging, premature or not I embrace it with gratitude, not everyone gets the chance.

  • Oh dear god yes. More than once I thought I feel like a 80 year old presumably does (perhaps worse) – in my late 30s. Exercise helps to some degree. but not really enough. Plus it’s starting to grate me that I invest in exercise, occasionally wipe myself out in the process to at best slow decline.

    To add insult to injury, I look really young – so much so, that I got carded occasionally when buying beer well into my 30s! People probably think I am a drunk teen when I stumble around on the street but then again, screw them.

    • Hahaha, I feel you. I also Look like I’m in my early twenties, but I have the problems of a 70 year old man specially bladder wise….

  • Cryptic transcription in mammalian stem cells linked to aging

    “In previous work, we showed that cryptic transcription in yeasts and worms is not only a marker of aging but also a cause,” said corresponding author Dr. Weiwei Dang, assistant professor of molecular and human genetics and the Huffington Center on Aging at Baylor. “Reducing the amount of this aberrant transcription in these organisms prolonged their lifespan.”

    https://medicalxpress.com/news/2021-08-cryptic-transcription-mammalian-stem-cells.html

    Also any kind of chemotheraphy will age you faster

    I fast an work out 4 to 5 days a week

  • To be honest this post was the most depressing thing to read, as it offers the problem but not what pwMS can do to make things any better (especially if we have done everything treatment wise already). Having had Lemtrada and reassured myself that being relatively fit with NEDA had meant I had headed things off, your post makes me feel a bit hopeless if I am honest. I normally find them useful but this one has made me think there are things it’s better not to know and I think I will unsubscribe.

    • Alison, don’t worry about this post. This is what happens to normal people. Tragically life is a sexually transmitted age-related neurodegenerative disease with 100% mortality. I am suffering from this disease as I type this. We can’t prevent ageing, but only hope to slow it down. Please remember that getting old is a privilege and not an affliction.

      • Quite right.
        Reaching old age is a privilege and I count myself very lucky that I can still enjoy it and am still active (mid seventies and ppms). It really is not as terrifying as some of you fear although it is not as they say for the faint-hearted.

        What can be done to keep decay at bay? Well, everything about ageing well for the general population (New Scientist is a good source) works for us as well and is good for brain health.

        One word of advice. For those of us for whom running is a distant memory, ‘body hacking’ is not the only way. You get the same benefits from say lifting a 1kg weight ten times as one a 10 kg once. It just takes longer. And 80% of the benefits of any activity social or physical comes from tha first 20%. The rest is merely the icing on the cake.

      • Thanks- I get that everyone ages. It’s the idea of premature ageing (the topic of your post) – without a hopeful element – that’s depressing. I’m 52, my children are 14 and 10 – I’m not ready to be physically/mentally old yet! Going through lemtrada was a big deal, trying to live healthily takes effort. Your post made me feel like what’s the point? Having no ongoing symptoms, having MRIs that show NEDA, these things give us HOPE. But reading your post today was like getting my diagnosis all over again ☹️

    • Alip,

      I’m with you on this. When you use every tool in the toolbox to fight this disease and are basically told that

      “I simply say these people have smouldering MS, but I suspect a large part of what we are seeing is age-related neurodegeneration that is occurring decades early than it should because MS has shredded their brain and cognitive reserve.”

      I’ve no objection to Prof G’s honesty, but these observations are just heartbreaking / demoralising to an MSer who is 50+.

      • Its equally demoralizing and frankly depressing to an MSer who is 60+ . I too have used the tools available to me and added tools as data became available to support their use in MS’ers. And now I’m learning that despite my best efforts, I have one foot in the grave, maybe more, along with the blessing of accelerating degeneration. WTF! I had hope and optimism that I could live a normal lifespan based on my genetics. Thanks for killing that Prof. G.

  • I can recommend a book called ‘Supercharge Your Brain’

    By Professor James Goodwin

    It’s gives you some good tips and advise and information on your overall brain health, a pretty good book, I got the audio version and enjoyed it. I believe James Goodwin is special advisor to the global brain council, also some association with Age UK aswell as other brain charities etc

    The book talks about, diet, exercise, gut microbiome, meditation. All sorts, but it’s easy to understand

  • There are some biohacking protocols that various people have come up with to attempt to slow aging. The Mayo clinic is currently doing a clinical trial of high-dose fisetin (a cheap supplement) for this very purpose. I know of another that attempts to hack the body’s QC process for mitochondria in order to remove large numbers of ones that have become defective, and another that attempts to improve endogenous stem cell pools. Many users on longecity have reported positive results. I wonder if MS patients could benefit from adopting some of these strategies.

By Prof G

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