Lipids Also An Aging Clock? Scientists Find That Simple Daily Activities Can Reduce This Aging Hallmark

Lipids Also An Aging Clock? Scientists Find That Simple Daily Activities Can Reduce This Aging Hallmark

Author: BalanceGenics Anti-aging Research Team (How100.com)

 

Aging is always accompanied by various changes in the composition of our body, in our youth, 10% of our body weight is bone, 30% is muscle, and only 20% is fat, but age is not forgiving, and in old age, it becomes 8% bone, only 15% muscle, and the fat even skyrocketed to 40% [1]!

In terms of where it accumulates, it is mainly abdominal fat that gradually increases during aging, and in terms of lipid types, it is mainly triglycerides that accumulate in fat cells, which are highly related to our daily energy consumption.

At the University of Amsterdam, Riekelt H. Houtkooper's team studied the changes in more than 1,200 lipids as we age, and they found that a type of lipid called bis(monoacylglycerol) phosphate (BMP) steadily accumulates in the body as we age [2].

 

But is this lipid, BMP, good or bad? If it's bad, is there a way to lower its levels? These are the questions that this article will answer.

 

  1. Why is BMP Different?

 

There are many types of lipids other than fats (triglycerides) (see table below) and many accumulate or decrease with aging, like the more common cholesterol, leukotrienes (mediators of intercellular signaling), and gangliosides (one of the components of the cell membranes of the nervous system), which increase, increase, and decrease with aging, respectively [3,4].

However, the aging process of these lipids is not necessarily stable; for example, a lipid that may increase with age in organ A, but decrease with age in organ B. There is one lipid, however, whose levels generally rise with age in all tissues and organs in mice: bis(monoacylglycerol) phosphate (BMP), which is a type of phospholipid.

If cholesterol is a simple lipid, then phospholipids are complex lipids, but even among phospholipids, BMP is definitely an anomaly. The ordinary phospholipids are easily degraded when they encounter phospholipase, but BMP does not eat this, it relies on its special structure and has a certain resistance to phospholipase, so BMP is more likely to accumulate more and more over the years.

 

Note: Left is the molecular structure of cholesterol, right is the molecular structure of dioleoyl-BMP (a type of BMP).

In addition to mice, the researchers found that in humans, BMP changes in a similar way, and that BMP-like lipids accumulate significantly with aging in both men and women.

In fact, there are many types of lipids that accumulate with aging, and BMP lipids stand out because they make up 10.5% of the lipids whose content increases significantly with aging. Without the qualifier "increases significantly with aging", BMP lipids make up only 2.5% of the total lipids. BMP is an excellent marker of aging.

 

 

Note: The red dots in panel A represent lipids that increase significantly with aging, and the blue dots represent lipids that decrease significantly with aging; the red dots in panel B indicate those lipids that increase significantly are BMP-like lipids.

 

  1. BMP: Good or Bad?

 

But after all that, what exactly is the role of BMP in our bodies? Phospholipids are the main components of the cell membrane structure, and BMPs as phospholipids are mainly found in the membranes of the organelle lysosomes (the cell's "garbage disposal station").

 

Source: NIH website

BMP helps lysosomes function properly, but most of the time BMP plays a less-than-flattering role, with high BMP levels commonly associated with neurodegenerative diseases, lysosomal storage disorders, cancer.

But despite this, the authors of the paper also show that with the limited research available, it's not possible to say that high BMP levels are a driver of disease or aging; it could also be a result of the body's efforts to maintain our physiological homeostasis in a state of disease or aging.

In addition, other researches reveal that BMP signaling plays a complex role in the aging process.

In the brain, an age-associated increase in BMP signaling inhibits hippocampal neurogenesis. BMP2, BMP4, and BMP6 mRNA and protein levels increase in the hippocampus with age. BMP4 is expressed in endothelial cells and localizes to the vasculature, while BMP6 primarily colocalizes with microglia. Genetic inhibition of BMPs via Cre-inducible BMPR1A knockout in the hippocampus of aged mice led to increased neurogenesis, signifying that a blockage of BMP signaling can partially restore neurogenesis in the aged brain.

However, the relationship between BMP signaling and cellular senescence is not straightforward, as TGF-β, which shares signaling pathways with BMPs, has been shown to induce or accelerate senescence in various cell types.

 

 

  1. How to Reduce BMP Levels?

 

In any case, the like-for-like nature of BMP and these aging-related symptoms/diseases have put it on the shelf in an awkward position, and for this reason, the researchers in this paper also explored ways to control BMP levels during aging. They found that exercise reduces BMP levels.

The first thing our body uses up during exercise is the easily available glucose, after that, it's our turn to consume the triglycerides that are hidden in the adipose tissue as energy storage units, which are broken down into fatty acids and glycerol and then further oxidized to produce ATP, giving us continuous power.

But the phospholipids including BMP said: we just constitute the cell membrane, but not so much energy for you to burn ah! Therefore, the reduced BMP levels cannot be generalized with triglycerides.

Although scientists have yet to understand the principle that exercise can reduce BMP levels, some studies have shown that exercise can make a significant change in the percentage of lipid components of the cell membrane [5], for example, the level of phosphatidylinositol (which is a phospholipid just like BMP) in the cell membrane will be reduced because of exercise [6], so the reduction in the level of BMP may also be a similar mechanism at work.

Since the principle of exercise lowering BMP levels may not be the same as fat loss, would the effect of BMP lowering still be related to the amount of exercise? Is it possible that all I need to do is swing my legs once in a while and the BMP army will retreat? This was explored somewhat by the authors of the paper.

The researchers designed three regimens for subjects to strictly implement, which gradually increased the intensity of exercise:

 

Option I was the least intense: 13 hours of sitting, 1 hour of standing and 1 hour of walking per day;

Option II was moderately intense: 9 hours of sitting, 3 hours of standing, and 2 hours of walking per day;

Option III was the most intense: 11 hours of sitting, and 1 hour of standing, walking, and exercising per day.

 

Figure Note: The pie charts in Figure a represent the percentage of time spent on each type of behavior in the three regimens

 

The results came back that the more intense the exercise, the more BMP dropped (BMP was even one of the lipids that decreased the most after exercise). However, considering that the experiment was designed primarily for post-menopausal women, these protocols may be slightly conservative, and readers who can afford it may want to step up their efforts, which may yield even better results.

 

In addition to exercise, we actually have a tastier option - a bit of fatty fish like salmon or sardines, or supplements like Balancegenics’ Krill Oil, which are rich in DHA (the fish oil component, the prettiest of the Omega-3 fatty acids), which has been shown to lower BMP levels in the body [7].

 

And, DHA's talents go far beyond that; for example, DHA intake has been shown to have great benefits for cardiovascular health, as well as improving brain and visual function and even preventing asthma [8]. 

 

BalanceGenics:  Personalized One-Stop Anti-aging Platform (How100.com)

 

Launched in California in 2018, BalanceGenics ("How100") started out as a solution to our own needs. Our team consists of seasoned health experts, doctors, and entrepreneurs with a common interest in anti-aging.

We use the latest findings from global leading longevity scientists to develop products and services.

BalanceGenics' Mission is to  create personalized solutions to live longer but stay younger. 

We will be your personalized one-stop anti-aging platform and help you stay younger for longer

 

Reference:

 

[1]Rudman D. Growth hormone, body composition, and aging. Journal of the American Geriatrics Society 1985; 33:800–807.

 

[2]Janssens GE, Molenaars M, Herzog K, Grevendonk L, Remie CME, Vervaart MAT, Elfrink HL, Wever EJM, Schomakers B V, Denis SW, Waterham HR, Pras-raves ML, et al. A conserved complex lipid signature marks human muscle aging and responds to short-term exercise. Nature Aging 2024.

 

[3]Tsugawa H, Ogasa K, Iwanami S, Hori A, Mikiko R, Riken T, Yamada Y, Aki R, Riken M, Arita M. A lipidome landscape of aging in mice 2022.

 

[4]Yu-ron Z. Leukotriene and Biological Organism Aging. Journal of Nanchang University 2015.

 

[5]Helge JW, Ayre KJ, Hulbert AJ, Kiens B, Storlien LH. Regular exercise modulates muscle membrane phospholipid profile in rats. The Journal of Nutrition 1999; 129:1636–1642.

 

[6]Ouyang P, Jiang Y, Doan HM, Xie L, Vasquez D, Welti R, Su X, Lu N, Herndon B, Yang S-S, Jeannotte R, Wang W. Weight Loss via exercise with controlled dietary intake may affect phospholipid profile for cancer prevention in murine skin tissues. Cancer Prevention Research (Philadelphia, Pa) 2010; 3:466–477.

 

[7]Bouvier J, Zemski Berry KA, Hullin-Matsuda F, Makino A, Michaud S, Geloën A, Murphy RC, Kobayashi T, Lagarde M, Delton-Vandenbroucke I. Selective decrease of bis(monoacylglycero)phosphate content in macrophages by high supplementation with docosahexaenoic acid. Journal of Lipid Research 2009; 50:243–255.

 

[8]Miyata J, Arita M. Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases. Allergology International : Official Journal of the Japanese Society of Allergology 2015; 64:27–34.

 

[9]Yousef, H., et al. (2015). Age-Associated Increase in BMP Signaling inhibits Hippocampal Neurogenesis. Stem Cells, 33(5), 1577-1588.

 

 

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