Living forever
Immortality is 'trending'; overly rich Silicon Valley types inevitably want to stay young forever and, as it were ever thus, are creating their own elixirs to do just that. Countless column inches in the popular press document their systems and photos their 'buffed' 50 yr old bodies.
Doomed to fail? yes of course they will fail, the selfie-mirror always lies until the day it doesn't! The elixirs are always a new take on 'drinking the blood of a young virgin' The pudding's proof won't be visible until they reach over 80, so a way to go.
However, impressive longevity has already been achieved in animals whose ancestors originate in both great animal phyla, namely the dinosoaurs and the mammals. Specifically the improbably long lived are found among the birds and bats.
And we know pretty much why they live so long.
Mitochondria and Entropy
At a thermodynamic level the viability of a cell depends on it having low, and in a complex system such as a cell, a highly improbably low value for its entropy. Such a state is achieved only with a substantial input of energy and in energetic terms, entropy at a given temperature, is represented in a form of energy called Gibb's Free Energy ΔG. That energy is supplied for the most part (by a very long way in fact) ... by mitochondria. Mitochondria are the Free Energy generating machines that make the improbability of complex multicellular life possible.
Having established above the absolute importance of mitochondria in maintaining the energy requirements for life of a cell and thus in overall terms the whole organism, it is important to take in the fact that mitochondria are also responsible for cell death, or apoptosis as it is called. The suicide death of a cell is initiated by mitochondria in response to its decrepitude, redundancy, infection, or cancerous change. No wonder then that one of the first tasks of a virus or cancer is to shut down mitochondrial reproduction and operation before the cell itself is shut down.
Living with a furnace
Having the dictator's power of life or death is one awesome thing, but what are the downsides of such absolute power? That's easy to answer. Mitochondria produce Reactive Oxygen Species (ROS) as an intrinsic part of their operation. ROS are very destructive free-radicals. It's a measure or their seriously destructive nature that the fastest and most abundant enzymes in a cell are dedicated to ROS neutralisation ( viz catalase and super oxide dismutase) and tellingly, most of the mitochondrial vulnerable genome has been 'outsourced' to the relatively safe environment of the cell's nucleus! No wonder then that ROS damage is cited as a major factor in the deleterious changes in cells that we associate with aging and is by the way, directly responsible for the rise in dietary antioxidant supplements in the hope of mitigating ROS damage. Also by the way these supplements don't work they just mess up the repair signalling pathways.
Mitochondria not only wield the power of life and death of a cell but are aslo at the root of its demise. So the question is begged as to just what can be done to ameliorate the downside and enhance the upside of these amazing structures that once were free living bacteria-like organisms which somehow joined forces with the proto-cells and made complex multicellular life in an oxygen rich environment possible.
Ideal Mitochondria
Mitochondria in young cells compared to their counterparts in old, senescent cells are in general, smaller, more plentiful and more tightly coupled. Being 'coupled' refers to the ratio between 'food' and oxygen input and chemical energy output. It's a measure of max power output for a given input. An analogy with a car's engine would be along the lines of say both cars delivering a 100 mph output but Car A doing so at 2000rpm and 50mpg wheras Car B does so at 6000 rpm and 25mpg. A fully uncoupled Car C would be stationary, reving away, burning fuel and getting very hot.
Earlier in this article I referred to mitochondria in birds and bats. In these surprisingly long lived animals ( record examples :birds 60-80 years, bats 30-40 yrs) indeed their mitochondria are small, plentiful and tightly coupled. So no surprises there.
In our own somatic human cells as the cell ages there are fewer of the 'young' mitochondria and more damaged larger mitochondria. It's time to pause here. Clearly when we are old we may not feel so energetic but we are still alive, so enough energy must be being produced to maintain the vital functions of a cell and hence the organs in which they operate. We do not need to use intense amounts of energy to live but birds and bats do ... simply to fly needs huge energetic output. The point I am making is we can survive carrying 'rubbish' mitochondria but they cannot.
Flat out to stand still
Mitochondria use an electrochemical system to produce the chemical energy the cell needs. It does so by harnessing energy stored in an electrical potential difference ( ie a voltage) across its membranes. This voltage has a threshold below which no energy is prodcued but above that threshold it can make chemical energy in the form of ATP molecules. Aging mitochondria, to keep going, can reduce their total membrane surface area and enlarge to make it easier to reach the voltage threshold but it's at the expense of capacity. Ie the 'battery' has enough power to light the LED but keep it on too long for energy and it fails quickly.
When mitochondria are fully powered up with a high voltage they work well prodcuing energy but generate a lot of ROS. An aging cell has to run its viable mitochondria flat out to meet the cell's minimum demands. In bats however ( and probably birds) the mitochondria are not running flat out, instead they are partially uncoupled, that is they are being a little inefficient. However the pay-back is huge. Vastly fewer ROS species are produced and cell damage is reduced dramatically both to the cell and the mitochondria. Going back to the car analogy it's like my low reving big engined Volvo versus a small commuter car both doing 70mph on the motorway. One engine is at 1800 rpm the other at 4500 rpm. Which one do you expect to reach 200,000 miles intact?
What to do
Finally then going back to the start of this post. What should our potential 'immortals' be doing? Answer: to become more bat-like.
Here's my list:
To encourage lots of small, well coupled mitochondria:
periodic intense demand for energy
Near-infra red radiation ( see previous posts)
To give mitochondria 'spare' capacity:
stimulate mitochondrial energy cycle with intermediates like malate
facilitate transport into mitochondria with B vitamins and CoQ10
facilitate acetyl unit uptake with acyl carnitine
These steps won't make them immortal but just maybe will keep them young and live longer active lives. The selfies and death certificates will judge the outcome.
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