Mid-Life Chronic Inflammation Contributes to Measures of Late Life Frailty

Chronic inflammation is a feature of aging. Constant unresolved inflammatory signaling arises from a number of distinct causes, but leads to significant disruption of cell and tissue function, and contributes to the onset and progression of age-related disease. The list causes includes a growing population of lingering senescent cells, all secreting pro-inflammatory signal molecules that can be useful in the short term, but become harmful when sustained over the long term. The list also includes some of the consequences of mitochondrial dysfunction, wherein fragments of mitochondrial DNA are found in the cytosol or outside cells, where they can provoke the innate immune system due to a similarity to bacterial DNA.

In today's open access paper, researchers show a correlation between degree of chronic inflammation and later progression towards lack of physical capacity and frailty, as assessed by gait speed. The data captures a modest decline in physical function in people who are not earnestly sick. For context regarding the numbers given, the average gait speed for people in their 60s and 7ps is 124 cm/s, and thus high measures of inflammation markers in mid-life predicts an average ~8% decline of physical function over the next 20 years. Human epidemiological studies struggle to show correlation, but causation is largely well demonstrated in analogous animal studies. Chronic inflammation is an important problem in the biology of aging, and effective solutions are very much needed.

Associations of mid-to-late-life inflammation with late-life mobility and the influences of chronic comorbidities, race, and social determinants of health: The Atherosclerosis Risk in Communities Study

An estimated 15.4 million older Americans are unable to walk two to three city blocks. Poor physical function, such as slower walking speed, leads to poor quality of life, institutionalization, incident disability, high healthcare costs, and high mortality in community-dwelling older adults and is considered the "sixth vital sign" for older patients. The underlying mechanisms contributing to slowing gait speed and dismobility are poorly understood. One potential pathway is direct inflammatory effects on muscle and other tissues, leading to wasting and weakness, triggering pathways that contribute to muscle breakdown, fatty infiltration, and fibrosis which can lead to muscle weakness, inefficiency, and mobility disability.

High levels of interleukin-6, high sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNFα), and TNFα soluble receptors are associated with slow walking speed and frailty primarily in older adults, supporting a role for inflammation on age-related mobility declines during late-life. However, whether chronically elevated levels of inflammation prior to older age, when interventions could be more effective, are associated with late-life mobility has not been well studied. Most studies only examined inflammation measured during older ages and did not consider duration of exposure from midlife, which would provide stronger evidence for causal mechanisms. Furthermore, relating inflammatory markers measured across the mid-to-late-life transition on late-life mobility could identify earlier intervention opportunities, yet studies of inflammation during this critical period are limited, particularly in diverse populations.

Among 4,758 community-dwelling participants in the Atherosclerosis Risk in Communities Study (ARIC), high-sensitivity C-reactive protein (hsCRP) was measured over 20+ years: in midlife at study visit 2 (V2: 1990-1992, 47-68 years); at visit 4 (1996-1998, 53-74 years); and with concurrent late-life 4-meter gait speed at visit 5 (2011-2013, 67-88 years, mean 75 years). We examined associations of late-life gait speed with midlife hsCRP (visit 2 continuous and clinically high ≥3 mg/L), with 20-year hsCRP history from midlife (visit 2 to visit 5 average continuous hsCRP and clinically high ≥3 mg/L) and with inflammation accumulation (visits and years with high hsCRP).

High midlife hsCRP was associated with slower late-life gait speed, even among those without chronic conditions in midlife: -4.6 cm/s. Importantly, sustained high hsCRP was associated with a 20-year slowing of -10.0 cm/s among those who never experienced obesity, diabetes, or hypertension over the 20-year period. Inflammation in midlife may contribute to clinically meaningful late-life slowing of gait speed, even among otherwise healthy-appearing adults. Regular monitoring and interventions for inflammation may be warranted from midlife.


I wonder if exercise and/ or cr diet would minimize or mostly avoid this issue. Thoughts?

Posted by: Robert at June 19th, 2024 5:08 PM

Robert, it certainly can't hurt :)

Ultimately though, no.... The world's fittest people eating a low-inflammatory diet will still develop senescence, immune system decline, and their chronic inflammation will increase.

Kinda related: https://youtu.be/bax8to_s07Q?si=qVKZm1LLwOzRkYIn
Brian Johnson just took a "Follistatin" gene therapy from a company called miniCircle in Prospera, Honduras: https://minicircle.io/our-therapies/

Posted by: Gregory Schulte at June 20th, 2024 12:17 PM

@ Gregory, yes, for about 20K. I've been putting in notes on some anti aging treatments and may pursue some of these treatments, possibly Peter Diamondis " Fountain" clinic. Peter been advertising his deep dive into some of these treatments.

Posted by: Robert at June 20th, 2024 3:18 PM

Looking at the direction this world is going, I am not sure if trying to extend one's lifespan makes sense or will work.

Between the toxic environment we now all live in, the wars that are being perpetrated, new pandemic viruses and the killer "vaccines" that follow, I think our fate has already been sealed.

In my opinion, just live life to the fullest instead of worrying about how you might be able to live a few more years longer as it likely will all be in vain.

In other words, live for today as tomorrow may never come.

Posted by: Jim at June 23rd, 2024 2:54 AM
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