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
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.