The research suggests aging isn’t strictly temporal, not solely about minutes and years passing. Once considered a steady, predictable decline, affecting everything in our bodies, everywhere, all at once, aging is much more haphazard than we once thought, starting in different parts of our bodies at different times, possibly long before we’re even thinking about aging.
It’s also personal, occurring at a unique molecular level inside each of us, and the process may be partially within our control. Once we know how our own organs are aging, we may be able to brake or speed that process by how we live.
I sometimes remark to my screen when I read comments like “Once considered a steady, predictable decline” – who could possibly have imagined that biology is complicated? The idea that understanding the complexity is useful I’m on board with though.
If biological age is driven by the average mitochondrial quality in each cell and the number of senescent cells, then each cell has its own age or position in development.
We know that different organs age at different rates depending on their levels of stem cells. The lower the levels of stem cells, the more disordered the organ becomes. Since all our organs undergo constant renewal and remodeling, those with lower levels of stem cells have increasingly poor renewals, eventually leading to senescent profiles and deterioration. Stem cell levels are set genetically, although you can somewhat impact the rate of exhaustion - generally increasing stress on an organ leads to faster stem cell exhaustion and subsequent aging. Different stresses impact organs differently, like alcohol impacts liver more than lungs, smoking lungs more than liver etc. But yes, aging is not uniform in the body and depends on multiple factors, many of them set genetically, others impacted by stressors.
I think this starts with stem cells failing to differentiate properly (and turning senescent) that has the effect of depleting the replacement of somatic cells. I think what actually happens is the senescent cells store fat (not necessarily always, but often).
This is mostly not true. The aging rate of most of our organs has little to do with their levels of stem cells. Only a minority of our organs are constantly renewing and remodeling by use of stem cells. Most have very limited capacity to renew and some hardly renew at all. Just look at the lack of success of stem cell treatments for aging in animals. Stem cells are more useful to repair injuries than to stop aging, although they are important still of course.
That’s not the main problem either, although it could play a role in some cases. For the most part, the stem cells aren’t supposed to replaced old cells in the first place. So blaming lack of stem cells is unfounded here. The exception is tissues that are constantly being renewed by stem cells, such as epithelial tissues or blood cells.
Perhaps. Yes there are definitely more exceptions that I forgot or am not aware of, but as a general rule many of the most important organs aren’t regularly regenerated with stem cells.
It is a hallmark of aging, but only one of many hallmarks. It’s very important in some organs, much less so in others. Take the brain as an example. Neurons in the adult brain are largely fixed and or not being replaced by stem cells. Also if you look into studies on stem cell infusions, the stem cells can help repair injuries but they usually don’t do much at all to old tissues.
My reasoning for stem cells not being of major importance for aging of much of the rest of the body is based on the limited regenerative capacity of some major organs. Examples of organs that have cells that are not actively replaced by stem cells during aging are skeletal muscles, heart muscles, cartilage and kidney glomeruli, and probably much of the vascular system aside for maybe the endothelium. In contrast, I think stem celsl would be more important for the tissues that are actively being replaced by stem cells throughout life. These would be mainly all the epithelial tissues, such as the skin and the intestines, and also the liver, the bone marrow and all the blood cells created from hematopoietic stem cells in the bone marrow. The potential for stem cell treatments is great for the bone marrow, because younger hematopoietic stem cells would be able to rejuvenate partly the immune system.
Beside aging of organs, I’m actually quite concerned about elastin, which is not regenerated and is only produced until late adolescence. it provides elasticity to vital organs and is on the critical path if you make it to ~ 120.
I’m quite concerned about that too. No interventions (including stem cells) fixes the elastin to a large degree.
Thanks. Looking briefly at this one I note these quote from the full text article:
"Compared with younger mice, old mice (20–24 months of age) showed a significant decrease in MuSCs along with fiber atrophy, but geriatric mice (28–32 months of age) showed no further loss of MuSCs when multiple sarcopenic symptoms increased (Sousa-Victor et al., 2014). Considering the conflicting evidence, it remains controversial whether the loss of MuSCs directly causes sarcopenia, although MuSCs are thought to be the sole source of new muscle nuclei and there is an inextricable link between the decay of MuSCs and poor muscle progression.
Fry et al. (2015) observed significant muscle mass loss only in flounder muscle after induced depletion of MuSCs from adult mouse skeletal muscle. In aged mice (24 months old), muscle atrophy consistent with criteria for human sarcopenia was observed in both control and MuSC-depleted groups, indicating that MuSC-dependent loss of regenerative capacity in adulthood does not accelerate sarcopenia in aging mice"
It looks like the muscle stem cells mainly help indirectly, or work to fix severe damage, such as loss of muscle cells caused by injury. They probably do less for sarcopenia in the absence of major injuries.
My own view is that there is a developing problem of getting Stem Cells to properly differentiate into functional somatic cells and they end up senescent and to some extent functioning as adipocytes.
This applies across the body where there is normally a process of renewal. I think that is why senescent cells tend to be found moreso in the body where it undergoes renewal.
You’re claiming that many cell types in many tissues don’t get replaced after some developmental stage. Not to say this is not true, but what is the evidence? As far as I know, there’s no accepted way to directly measure the age of a cell which can be applied on a single cell level across a tissue. (If I’m wrong here, please correct me!)
Just to clarify, many if not most cell types can be replaced, but the replacement is very minimal in many types of tissues and sometimes only occurs in response to injury. Prime examples of cell types with little to no replacement in adulthood are neurons and heart muscle cells. There are many others that perhaps can be replaced partially but don’t normally do so to a significant degree unless in response to some major injury. Skeletal muscles are likely an example of this.
Here are some quotes from on this:
“Strikingly, we also found that a subset of fibroblasts and endothelial cells, both known for their replicative potential, are characterized by the absence of cell division during adulthood.”
“The lifespan of a terminally differentiated cell is quite variable among organs: 3 to 4 days for epithelial intestinal cells, to olfactory neuronal cells replaced from basal stem cells, to a life time for the majority of neurons, cardiomyocytes, and all inner hear hair cells (De Anda et al., 2016; Brann and Firestein, 2014; Foglia and Poss, 2016; Steinhauser et al., 2012; Zhang et al., 2012). In some cases, somatic stem cells can respond to tissue damage and proliferate according to tissue-specific needs, as in the striated muscle, which can somewhat regenerate after wound because of activation of its satellite stem cells (Blau et al., 2015).”
“The adult human heart does not regenerate significant amounts of lost tissue after injury. Rather than making new, functional muscle, human hearts are prone to scarring and hypertrophy, which can often lead to fatal arrhythmias and heart failure. The most-cited basis of this ineffective cardiac regeneration in mammals is the low proliferative capacity of adult cardiomyocytes.”
The idea that understanding the complexity is useful I’m on board with though.
