Cellular Senescence in Brief

Posted by Benjamin Buller on

Forever Labs was founded on the principle that each of us has a valuable reservoir of bone marrow cells, and that as we age this reservoir is depleted, much like an extended drought that has depleted Lake Powell in the Southwest. Las Vegas and Phoenix grow and grow, it rains less and less, and the river can’t keep the water level high enough to meet demand. I think this is a salient analogy of what happens in our bone marrow as we age. As we grow, get hurt, repair damage, etc., our cells divide and migrate around the body as needed. However, this special reservoir starts to diminish as these cells lose their ability to divide with each passing year. The analogy breaks down here, though, because a drought can be solved with more rain. Our cells, once they enter “senescence,” cannot be rescued by any known mechanism. In this post, I’d like to talk about senescence: what it is and why it’s a fundamental part of aging. 

Cellular senescence refers to the point at which cells cease to divide. In culture dishes, it has been shown that cells will normally divide 50 times on average and then stop. This happens because of deterioration at the molecular level, and, so far as we know, it is a permanent condition. That is, once a cell is senescent, it cannot be coaxed to behave normally again. Biologically speaking, there are good reasons for this. Every time a cell divides, it accumulates a little bit of damage (e.g. in DNA). This damage is cumulative. A tiny bit of damage to one cell is normally harmless. But, after successive cell divisions, damage accumulates to a point that the cell shuts down. Senescence probably evolved as a mechanism to ensure that cells don’t divide out of control, leading to all sorts of disease. For example, when cancer occurs due to the continued expansion of cells that have accumulated heavy damage. 

Research has shown that, in bone marrow MSCs, the number of times a cell divides can be affected by age. Studies in multiple animal types have produced conflicting evidence about the effect of aging on senescence in cultured MSCs, but the majority of studies have concluded that, the older the organism at the time of harvest, the faster they will enter senescence in culture. This supports my own experience culturing bone marrow cells. 

An anecdote is not data, so I don’t mean to confuse the two. But of course data are a lot more believable when they are validated by personal experience. I have cultured bone marrow MSCs from a number of monkeys.  From my experience, MSCs from older monkeys are more likely to yield an unsuccessful culture. Often times, the culture from older monkeys will appear to be normal for a short time, and then they mysteriously stop growing. Sometimes, this happens in as little as two “passages” (when cells grow to a point where they are covering the entire culture flask or dish they must be removed and seeded onto to new flasks at a low density; this is known as passaging). In contrast, cells from young-middle aged animals will most often have little, if any, noticeable difference after 8 or 10 passages. Just to remind our readers of the mathematics: this isn’t a fivefold difference, it’s a difference of 25, or 32, in terms of how many cells are grown. Therefore, even assuming that the cells are equally effective at treating disease (which as I have covered in other blogs, they likely are not), the number of healthy cells that can be derived from your own bone marrow is proportional to your age: as you age, your viable MSCs may be dramatically reduced compared with your younger self.

Anti-aging researchers are trying to find ways to combat senescence. One theory is that if the body can be programmed to rid itself of senescent cells, then healthy, non-senescent cells can replace the niche they occupy. It isn’t clear if this is possible or indeed desirable. I respect these efforts, and think it’s a worthy area of research. However, as a somewhat conservative thinker, I am always a bit skeptical of efforts to encourage unnatural cell division in humans. Remember, the upside to senescence is that it protects us from disease, most notably cancer. Returning to the reservoir metaphor, what we’re doing at Forever Labs is to give you a naturally derived drought solution: a water tower, separate from the main reservoir, which can be tapped into at any time of need.

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