Author Topic: Life expectancy  (Read 4183 times)

frankly frankie

  • I kid you not
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Re: Life expectancy
« Reply #50 on: 09 July, 2020, 08:47:31 am »
Youse lot do realise don't you, that you're all just figments of my imagination, and when I go** that's it, you're all gone too.  Pfft.

** the chances are rising daily.

That said, here's the story of one figment I was very attached to, my neighbour and very close friend.  He would weed my garden and I would mow his lawn.  He was a very outgoing and social animal and local political activist, the centre of numerous circles of friends, Paddy Ashdown would drop in for dinner (cooking was his hobby and he was he was exceptionally good at it - though he never ate or drank all that much himself). 
He retired at 50 (teachers, huh) and embraced an active lifestyle of walking the moors by day and being social in the evenings. 
In his early 60s the first mini-stroke set him back a bit, but he could still walk and talk and do simple computer things.  The second one totally altered his personality - wiping out all the nice bits and just leaving a thoroughly nasty man (who had always been there, hidden from view).  The third one reduced him to such a pile of shit that his wife (married 45 years) walked out and left him to die alone.  Which only took a couple of months.
when you're dead you're done, so let the good times roll

ian

Re: Life expectancy
« Reply #51 on: 09 July, 2020, 10:06:39 am »
ian, I think that is a really interesting summary.  Have you read "The sports gene" by David Epstein?

I haven't but I might. I suspect he didn't have Usain Bolt wading through treacle though, but if he's open to the experiment, I'm willing to put up a bag of hot chips...

I should also say, it's not genes per se, it's more often a case of how they're regulated. It's rare that a mutation in a single protein has a significant effect, those early days of thinking one gene = one thing, are mostly gone (though everyone likes the simple elegance of Mendelian inheritance). Traits (and dieseases) are complex polygenic things, but more importantly, our phenotype is the result of a massively sophisticated system that starts with DNA, which is filled with regulatory sequences (there's far more regulatory DNA than coding DNA), the DNA generate the RNAs that make proteins, but also lots of small RNAs that regulate that process, and then that is all turned into protein. Those proteins may be structural, enzymic, and in turn, may regulate, modify, and package DNA (and RNA and other proteins). Then there's biochemical, endocrine and physiological regulation at all levels from organelle to entire body.

That's why, despite being near identical to a chimpanzee at the genetic level, humans generally aren't mistaken for chimpanzees.

Anyway, it's complicated, so that's why you should furrow your brows when someone says they have the gene or genes for so-and-so. Once you get beyond Mendel's wrinkled peas it rapidly complicates. Even most 'cancer genes' only deal in probabilities. Probably the most famous, BRCA1, comes with a significant chance of breast cancer in women, the risk for carriers of the mutant cancer-related variants is something like 80% over 90 years (and around 50% for ovarian cancer). But some people with the variant won't get cancer. BRCA1, on the other hand, only causes modest cancer risk in men. There are lots of other things happening (the BRCA1 gene encodes a protein involving in fixing particular types of DNA damage, the mutations result in low levels (a total absence of BRCA1 is generally fatal at the embryonic stage), but that damage has to occur first, and then the failure to fix it has to become significant (and we have all kinds of DNA repair pathways, your DNA is being broken, damaged, and inaccurately copied all the time). Which is why it comes down to probability, damage accumulates over time.

Incidentally, Mary-Claire King, in whose lab BRCA1 (and the role of its variants in causing cancer) was uncovered in, spent her early career scratching her head and wondering why she couldn't, at the protein level, find significant differences between humans and chimps (initially she assumed she was doing the experiments wrong). Of course, that lack of difference goes all the way down to DNA (but the technology to easily sequence entire genomes had yet to come along). But we're pretty similar to onions for that matter.

Re: Life expectancy
« Reply #52 on: 09 July, 2020, 10:43:00 am »
I’m sure that others will disagree, but there are indicators in the animal world of “ design life”
Elephants live to about 60/70 ish . But, they have more sets of teeth ( 4 I think), and females breed up to the last few years.
Whales breed longer.
In biological terms, the only purpose of a generation is to provide and secure the next generation.
We typically now live much longer than our biological usefulness.

Improved medical care, nutrition etc has given humans a much longer life typically. However, I personally question expectations into 90s. You may be very lucky, but you may be nearer the left of the curve.

As genetic profiling etc make new discoveries I can see some “ fortunate”  people having to provide significantly more investment into their pension arrangements.

Re: Life expectancy
« Reply #53 on: 09 July, 2020, 10:59:51 am »
Youse lot do realise don't you, that you're all just figments of my imagination, and when I go** that's it, you're all gone too.  Pfft.

** the chances are rising daily.

That said, here's the story of one figment I was very attached to, my neighbour and very close friend.  He would weed my garden and I would mow his lawn.  He was a very outgoing and social animal and local political activist, the centre of numerous circles of friends, Paddy Ashdown would drop in for dinner (cooking was his hobby and he was he was exceptionally good at it - though he never ate or drank all that much himself). 
He retired at 50 (teachers, huh) and embraced an active lifestyle of walking the moors by day and being social in the evenings. 
In his early 60s the first mini-stroke set him back a bit, but he could still walk and talk and do simple computer things.  The second one totally altered his personality - wiping out all the nice bits and just leaving a thoroughly nasty man (who had always been there, hidden from view).  The third one reduced him to such a pile of shit that his wife (married 45 years) walked out and left him to die alone.  Which only took a couple of months.

Ooof!

On Monday we have the funeral of an old friend who survived to 77 against all the odds.  My first socially-distanced funeral.  I suppose that at least I only have to read to 20, rather than 100s.

ian

Re: Life expectancy
« Reply #54 on: 09 July, 2020, 11:52:47 am »
I’m sure that others will disagree, but there are indicators in the animal world of “ design life”
Elephants live to about 60/70 ish . But, they have more sets of teeth ( 4 I think), and females breed up to the last few years.
Whales breed longer.
In biological terms, the only purpose of a generation is to provide and secure the next generation.
We typically now live much longer than our biological usefulness.

Improved medical care, nutrition etc has given humans a much longer life typically. However, I personally question expectations into 90s. You may be very lucky, but you may be nearer the left of the curve.

As genetic profiling etc make new discoveries I can see some “ fortunate”  people having to provide significantly more investment into their pension arrangements.

In very simple terms, ageing is the balance between damage and repair. You start off in life with these two processes evenly matched but over time your start to accumulate damage faster than you can repair it (and the mechanisms that perform the repair are also subject to damage so the rates aren't linear). This is generally why animals with fast metabolic rates (shrews, bats etc.) have short lifespans and larger ones with slower rates (elephants, whales etc.) live longer. If you drive everywhere with your foot to the floor, that car probably won't last too long.

There's also the singular event. A mutation somewhere critical. A burst artery. That kind of thing. These may be immediately fatal, or have a significant impact on life expectancy. These are also probabilistic, so the longer you are around, the more likely they are to happen. The probability is also affected by those underlying ageing processes.

Evolution doesn't care about time. Your genes don't care about how long you live, just that they get propagated. There's no 'design life' as such, that's backwards, nothing is designed to live a specific time, life expectancy is an output. And as mentioned, though we're technically useless when we cease to reproduce, we effectively aren't, since the benefits continue (from building a society, looking after grandchildren etc.) to have an influence, so longevity can be selected for in that fashion. But there's no necessary evolutionary push for a longer life.

Humans meddle, of course, since we have medicine, can produce fresh water, and have a society that is (often) willing to invest in supporting itself as a whole. The biggest bumps to life expectancy are avoiding immediately fatal events (the biggest single effect on average life expectancy is that reducing the number of deaths of very young infants – you don't have to read back far to discovered that the expectation of any family was to lose a few children – and often the mother – in childbirth or at a very young age) – fatal disease and accidents.

Anyway, if we want to live longer, there's no simple genetic recipe for that, that's a part of the whole. I would suspect that any further increases in life expectancy would come from molecular interventions, beefing up those repair mechanism and supplementing our current abilities, removing known bad gene variants. I think it's inevitable at this point that we'll start to edit our own genomes (or at least those in the developed world) and it's not just about the quantity, it's adding more quality years.

ian

Re: Life expectancy
« Reply #55 on: 09 July, 2020, 03:10:04 pm »
Forget to write that the 'breast cancer gene' BRCA1 (and 2) is named after Paul Broca, the famous French anatomist (after whom Broca's area in your brain is named, but he was also the home of a lot of dodgy anthropological ideas, popular at the time). He formulated an idea that there was some hereditary disposition to breast cancer by working through the family tree of his wife, Adele, whose family had a high prevalence. Of course, they were a good century away from the idea of genes.

Ironically, she died in her late seventies and not from breast cancer, whereas he dropped dead in his fifties from a heart attack.