Studying Bacteria Provides Insight into the Origins of Aging
Aging came into being very early in the history of life, resulting from the evolution of strategies to deal with the inevitable accumulation of metabolic waste and damaged molecules in single-celled organisms: operating any sort of machinery produces wear and byproducts, and this is just as true of biological machinery. This can be seen in bacteria today, where cell division can shift most or all of the damage onto one of the daughter cells, using reproduction as a way to dilute waste and damage to maintain a core population that is pristine. The cost is a secondary population that is aging, becoming more damaged over time. These strategies were inherited by multicellular organisms, and show up in, for example, stem cell populations that must maintain themselves for long periods of time. There is a clear spectrum of collective action in mechanisms relevant to aging that reaches from the bacterial collaboration observed in the research here to the highly organized behavior of tissues and their stem cells in our species. At root, it is all about how to deal with damage, and aging is absolutely a matter of damage accumulation.
Microorganisms like bacteria reproduce by growing and dividing into two new bacteria. The older the bacteria, the more defects they have accumulated. When bacteria divide, the two new bacteria look the same, but the question is whether the defects are divided equally between the two new individuals. The researchers performed experiments in the laboratory and made model calculations. They wanted to investigate what was best for the bacterial community. Would it be best to have a colony that was aged to the same degree? Or would it be better for the colony to have the aging defects accumulate in some individuals, while others were free of aging defects and were thus younger?
In the laboratory they studied the bacterial colonies under different conditions and influences. The measurements showed that when a colony was left in peace, the bacteria shared almost symmetrically, so the new individuals were fairly similar with the same number of defects. However, if they exposed the colony to 'stress' in the form of heat or bacteriostatic compounds, cell division was asymmetrical. Now the defects gathered in one bacterium, which then aged and also grew at a slower rate. "What we have found is that the asymmetry of cell division is not controlled genetically. It is a process that is controlled by the physical environment. Through collective behaviour, the bacterial colony that is exposed to stress can stay young, produce more offspring and keep the colony healthier." This is a process that is probably universal and applies to cells in many organisms, including for stem cells. A single individual cell cannot overcome the damage, but the group of cells can do so together. The strength lies in the collective behaviour.
Link: http://www.nbi.ku.dk/english/news/news16/bacteria-avoid-age-defects-through-collective-behaviour/
This is NOT a matter of damage acumulation.
bacterias choose to switch the aging ON and OFF, depending on what is good for the population in the actual environment, but not for the sake of the individuum.
The mechanism of senescence (in this case: inducible asymmetrical cell division) is selected by evolution because the whole population profits by senescence.
Well whatever view you have on the origin of aging - the few bacteria that do not age, can only do so in the perfect conditions, and there is no such thing as the perfect conditions outside of a lab, keep that in mind - there is one fact everyone has to accept - we've evolved for a good 4 billion years with the imperative of accumulating damage.
For us accumulating damage IS the reality. There is no hidden mechanism surviving for that long in our DNA that can switch aging on or off.
So, any research we do in relation to anti aging should be very much focused on damage accumulation.
Josh Mitteldorf on animals that reverse aging: http://nautil.us/issue/36/aging/why-aging-isnt-inevitable
We do accumulate damage over time such as nuclear DNA mutations that can cause cancer. However the primary reason we get cancer more often in old age is that the mechanisms for preventing and repairing such damage are turned off. Various methods have been discovered to revert aged human tissue cultures to a younger state (e.g., iPSCs, activating TFAM or other regulatory factors, adding glycine, increasing nuclear NAD+). This indicates that the aged phenotype is not just accumulated damage. Josh Mitteldorf argues for programmed aging. Some for epigenetic drift or shortening of telomeres or signals released by senescent cells.
While all forms of damage will eventually have to be repaired I believe those that directly affect the cell aging phenotype will be easiest and first to succeed. Indeed George Church claims his lab has already had some success in mice.
@Annonymous: This paper says the contrary: https://www.fightaging.org/archives/2016/07/is-nuclear-dna-damage-responsible-for-stem-cell-aging/
Hi !
On the origins of aging and bacterias.
I believe that damage is a large part of the equation but not the entirety; programming/epigenetics are part of it too.
They go hand in hand. Though it's a bit of a chicken or egg thing, it is the damage that creates epigenetics changes (it seems so)
or is it epigenetic changes/program that creates damage in the programming process. Because we could say that damage is the byproduct
of the process of aging - which itself alters the course of epigenetics; because the human biological machinery is inherently flawed and
as such produces flaws during cell division, which end up as damage. Perhaps, if these 'genetic' flaws were removed, damage would be stopped.
There does not need to be 'rusting/oxidation', but in our case, our cells adapted to that reality by creating new-tailored/custom adaptations
on top of old adaptations if things presented problems (and they did, as the system is flawed from the get go, it's extremely complex and
impressive all of this works in unison (that cells know where to go how to comply how to work in groups and all of this happening at the same time, these
genes DNA codes that tell them signals/codes that they perfectly get. It's one immense and astronomically complex machine that alters itself.
It emulates the universe in space itself (our biology is an internal universe where we, our body, are, symbolically, the cosmos enveloppe)....and it 'works'..but it does not mean it is perfect, it has flaws, damage causing other damages, and
genes/processes causing changes which cause damage. Anyway you see it you can look it from any angle/side and it's all connected somehow.
Hence, the chicken and egg dilemma. I think the egg came first though (if it's the damage we mean) than the chicken/the chicken then came (the gene/programming) because
without that egg there would be no chicken (but, in reality, if speaking strictly about Chickens, chickens came first as they descend from dinos, dinos had eggs too, dinos descend from evolved lizards/water animals - the evolving animals came before the eggs (the eggs were a method of animal delivery/birth that evolved into it. The egg itself is a protection mechanism/a shield shell if you will, a very obviously 'evolved' birth delivery mechanism to protect the child and assure birth).
Damage is altering our genes, they then try to adapt to those problems (like for example,
evolutionary selected modulation of phospholipid composition to counter complex ROS. And even better example, protocells (the earliest form
of cell in unicellular organisms who date back to 4500 millions Y ago (4.5 Billion Years ago during formation of young Earth) were formed
with the laws of thermodynamics and diverse molecules that constitute us.
''The cell membrane is the only cellular structure that is found in all of the cells of all of the organisms on Earth.[12]''
''The three main structures phospholipids form in solution; the liposome (a closed bilayer), the micelle and the bilayer''
''Researchers Irene A. Chen and Jack W. Szostak (Nobel Prize in Physiology or Medicine 2009) amongst others, demonstrated that simple physicochemical properties of elementary protocells can give rise to essential cellular behaviors, including primitive forms of Darwinian competition and energy storage.
Such cooperative interactions between the membrane and encapsulated contents could greatly simplify the transition from replicating molecules to true cells.[4] Furthermore, competition for membrane molecules would favor stabilized membranes, suggesting a selective advantage for the evolution of cross-linked fatty acids
and even the phospholipids of today.[4] This micro-encapsulation allowed for metabolism within the membrane, exchange of small molecules and prevention of passage of large substances across it.[13] The main advantages of encapsulation include increased solubility of the cargo and creating energy in the form of chemical gradient.
Energy is thus often said to be stored by cells in the structures of molecules of substances such as carbohydrates (including sugars), lipids, and proteins, which release energy when chemically combined with oxygen during cellular respiration.[14][15]''
It's ironic because this encapsulation of cells, molded by thermodynamic laws on Earth and the cosmos, assembled using precise elements - water, carbs, oxygen, gases, nutrients, lipids...and, for example,
what do we see during animal evolution, massive evolutionary pressure and selection on membrane phospholipidome/reordering to reduce mitochondrial Complex I/III ETC ROS peroxidizability/susceptibility.
This means there are 'laws' at work - which create evolution of genes and damages as we know them, Forces of Nature at work if you will, an Invisible Tugg of War happening deep inside the infinitely small, Energy that Pushes in Pushes Out, some scientist say it is due to the energy
by the gravity. That without gravity and anti-matter there would be no life. Gravity - attracts, this gravitational force - is energy (in fact it was called 'God Particule' for a reason). It attracks
the elements together to 'compose' something new (a protocell or ancient bacterias like our bacterial-nature mitochondrias). Than lqter, a prokaryote and later eukaryotic cell. Much later in evolution, Earth populating with evolving animals full of these eukaryotes cells who die or live longer depending on their genetic make up and damage susceptibility. So if you were to ask me what drives what. I would say everything, but mostly,
these forces/cosmic thermodynamic laws of nature/space/universe that we only know a little about. Damage was selected as something good in early dying
animals, as a population control mechanism. This damage manifested by unimproved/unevolved or devolved/unoptimized Longevity Genes.
It's all of that, not one or the other...you can spin it anyway you like.
..'2 cents worth.
The Sequoia gigantea (lives up to 2500-3500 years or more), Sequoia sempervirens (1200-1800 years)(https://www.nps.gov/parkhistory/online_books/seki/stagner/sec2.htm) could nonetheless to escape mutational meltdown. A recent study shows that massive tree stature requires surprisingly few stem cell divisions, and that the mutational load is not proportional to stature, but to branching order. http://www.cell.com/current-biology/abstract/S0960-9822(16)30546-2
But is this the real reason for their longevity? Cuttings of of this trees, you can rejuvenate with the help of plant hormones and to plant in the ground. After the formation of the roots, the cells of the young plants are as young as those that are from the seed. http://onlinelibrary.wiley.com/doi/10.1111/j.1438-8677.2012.00622.x/abstract
http://www.cell.com/current-biology/abstract/S0960-9822(16)30546-2
@Dmitry
Hi Dmitry !
Exactly, there can be confusion (I am confused many times about all of this too) : that if the animal/tree is of a larger stature there must be more (stem) cell division going on or more cell density. It's not necessarily the case,
the confusion stems from mixing developmental growth with cellular growth. You can get very big (developmental growth/IGF) but it's not necessarily the same going on your stem cells.
That's why you can see an elephant or a sequoia tree reach their size (organismal growth) yet their cellular divisions do not match that. Cells can occupy
a volume (cell density) but that volume and Extra-Cellular Milieu (ETC) can also be altered to have more or less volume available - to fill it with cells (expansion/cell density/number per cubic micron); and as such transform the size of the animal/organism.
''But is this the real reason for their longevity? Cuttings of of this trees, you can rejuvenate with the help of plant hormones and to plant in the ground. After the formation of the roots, the cells of the young plants are as young as those that are from the seed.''
Yes, but also, I found out one of the main reason that non-clonal huge trees like Sequoia Trees, Baobab Trees, Gingko Biloba Trees, California Red Pine Trees, California Greatbasin Bristlecone pines (which lives 5000 years), Iran Cypres Trees, England 'If' Trees, and a couple of other huge ones;
is because they use plant hormones (Auxin) which activate telomerase in their Meristem cells in their trunk and roots (especially in the roots).
The best example, is the Great Basin Bristlecone Pine, which has cyclic 'bouts/rounds' of activation of Telomerase each something years (maybe each 10 years or so since its growth is so ultra-slow),
it doesn't any more than that - activating telomerase enzyme sporadically - to increase stem cell mobilisation and regrow new trunk rings/tree flesh/branches/leaves....
Telomerase is an enzyme used by many immortal animals who evade replicative cell lifespan death by confering it cell replicative immortality, as telomerase keeps on adding Telomere DNA bp repeats on the chromosomal end-termini telomeric DNA in cell nucleus of these stem-cells (our stem cells can't
use this mechanism and are bound by replicative lifespan reduction/if telomerase where activated it would increase stem-cell cancers; only two parts's stem cells use telomerase, gonadal testicular primordial germ/stem cells in male testicules of male before birth in mother's womb. The other ones, are the immune system stem cell such as bone marrow or lymphocytes who use telomerase (that's why it's so dangerous to remove telomerase from the immune system - it uses it, yet telomerase is highjacked by cancers (a double-edged sword, it's still better to keep it and have properly functionning immune system (NK-cell, T-Cells, Macrophages, White Blood Cells, Inteferon-gamma, Immunoglobulin...) that can eradicate these cancers in the first place).
One more thing, they use photosynthesis to get energy from the sun UVs, and all of these trees also have huge reservoirs of sugar molecules stocked in their tall reservoir-trunks from their deep below-ground roots extracting the grounds minerals/nutrient (resistant starch/sap/starchy sap) which they use as energy 'to continuously grow' over the centuries. These starches are used for DNA synthesis/building blocks and repair the tree's tissue during cell replication and chromosomal telomere elongation with their permanently active telomerase (through endocrinal vegetal production of plant Auxin).