
The New Old Age - prostoalex
https://thewalrus.ca/the-new-old-age/
======
claydavisss
My father retired from the fire department at fifty-three and has been
collecting a gold-plated pension for twenty years already, and will probably
get ten more years. Assuming my mother outlives him, she will collect ninety
percent of his benefits until she dies, possibly ten years further.

The pension plan includes full health benefits including dental. The monthly
payout is periodically adjusted for inflation.

How can retirement funds survive people working for thirty years and
collecting benefits for forty?

I'll say this - if you have yet to decide a career - pick firefighting!
Firefighters still have insane retirement plans almost everywhere, although
some are being converted to 401k as reality sets in. Maybe a very small
percentage of tech workers will have full _lifetime_ compensation anywhere
near what firefighters will have.

~~~
hutzlibu
Well, it is not everywhere as good as this.

But I would add, that compared to a tech workers, firefighters risk their life
at work. And exposition to toxic gases, etc. But I assume that the pension
compensation might be from a time when protection equipmemt was less
sophisticated..

~~~
DenisM
Pizza delivery workers risk their lives more than firefighters:

[http://www.slate.com/articles/news_and_politics/hey_wait_a_m...](http://www.slate.com/articles/news_and_politics/hey_wait_a_minute/2003/10/smoke_and_mirrors.html)

~~~
hutzlibu
Well, I guess nobody ever said, life is fair ...

But it would be actually nice, if we can arrange things a bit more
adequately..

------
3pt14159
As a Canadian (and Walrus print subscriber to boot!) this article shines a bit
of a bit-too-positive hue to the realties that we're starting to deal with.
Unlike our American counterparts, and thanks to the technocratic leadership of
the Chretien, Martin, Harper, and Trudeau Jr governments many long term
decisions were made that are going to soften the blow, but the reality is
we're going from a one-to-five retiree to worker ratio to a two-to-three.
Harper was great for our net-debt to GDP / and hospital expansion and the
Liberals before him made sure that the CPP was fully funded on an actuarial
basis and fixed our credit rating, but it's still going to be a brutal couple
decades financially.

Honestly the worst part isn't even the way it's hitting / going to hit our
healthcare / welfare[0] systems. The worst part is that due to the mental
effects of aging our electorate is getting dumber just when it needs to be
smart.

Against their own interests as a demographic, boomers voted in Doug Ford in
Ontario, the brother of former crack mayor of Toronto Rob Ford, and his plan
is to "find efficiencies" and bring back "buck a beer" whilst lowering taxes.

I'm starting to think that democracy needs to be adjusted either for mental
capacity, or for expected longevity. I wasn't able to vote when I was ten even
though I was taking college courses nights, weekends, and summers. I was fine
with it. I'd be fine losing the right to vote at 80 or 85.

It's just a second childhood. When I'm that age I can trust that my family
won't vote to take away my social assistance.

[0] Many seniors and soon-to-be seniors get on disability or qualify for OAS,
or qualify for other healthcare or housing programs not actuarially balanced
for demographic distortions.

Edit:

Never before have I made a comment that seems to oscillate so wildly with
upvotes and downvotes.

~~~
B1FF_PSUVM
> due to the mental effects of aging our electorate is getting dumber

Youth is well known for wise decisions ...

~~~
T-A
Sadly, 3pt14159 has a point:

[http://www.apa.org/monitor/2015/02/aging-
brains.aspx](http://www.apa.org/monitor/2015/02/aging-brains.aspx)

(though peak age in that graph is quite a bit higher than others you see
floating around).

~~~
3pt14159
Most of the research I've seen shows that mental capacity is strongest in the
30s where the decreases in fluid intelligence are minor compared to the 20s
and the gains in crystallized intelligence are measurable. It falls off a
cliff in your 80s.

But I really don't need a guy in a lab coat to tell me about mental capacity
and age. I'm old enough to have seen first hand what happens even to very
intelligent people.

I've only met one person that made it to 90s with a mind I would call fully
operable, and he was a well known and respected engineering researcher his
whole life. Most get stuck in a pattern of thinking that they can't break out
of. It's eery to observe the slide into it.

~~~
B1FF_PSUVM
> very intelligent people.

Good points, but I'm just pointing out that wisdom and intelligence are not
the same.

A wit once said he'd rather be governed by the first 400 names in the phone
book than by the Harvard faculty ...

~~~
3pt14159
I completely agree that they're different and I really do prize the wisdom of
others because I feel like its the weakest ability score on my character
sheet, but unfortunately the world is getting so complicated that obvious
solutions are ill-advised.

A wise person can see that Donald Trump is a villain because they understand
his character. An intelligent person can see that his policies produce
outcomes that are counter to their aims.

The trouble arises when you have someone that has good character; but is
misguided _technically_. They want to, say, help the poor so they nationalize
the farms or end trade agreements.

------
analognoise
I've thought about offing myself at 60. I watched my dad get old, and life
isn't really that fun anyway, so what is the point? To run the risk of
outliving my kids or finances?

I think I'll just hit the eject button early.

~~~
KineticLensman
I watched my father die when he was 59, after a decade or so of bad health
that meant he had to give up lots of his favourite hobbies.

I'm now 57. I have one or two minor health issues but (famous last words!) can
still do most of the things I want to. I've also decided which side of the
life-work balance I want to maximise (life, obviously) and have gone part
time, with the support of my employer. So I don't make the mistake of putting
things off until I retire, and then finding I don't have the capability to do
them.

I decided that the next time someone asks me how old I am, I'm going to say
positively 'almost 60' rather than 'late 50s' to show that I am still me and
not planning to shuffle off this mortal coil just yet. Even if my feet are
nailed to the perch, as it were. I'd change my mind for certain categories of
disease, but there is no way I'd set an arbitrary limit.

------
reasonattlm
The present rate of increase of life expectancy at birth is 1 year every 5
years. The rate of increase of life expectancy at 65 is 1 year every 10 years.
These are highly artificial measures, a metric of what will happen if
technological progress freezes at its present point.

Technological progress will not freeze. Past increases in life expectancy due
to slowing of aging (versus control over infectious disease to reduce early
life mortality) have been incidental, not intentional. They arguably largely
arise from that control over infectious disease. But the research and
development community are now transitioning into a deliberate targeting of the
mechanisms of aging. The difference will be night and day. Great
discontinuities in the curve of life expectancy lie in the near future, upward
leaps of five years here and ten years there as therapies that repair the root
causes of aging become available. Senolytics will be the first of these -
already something that the adventurous can get out there and try. There will
be many more.

\---------------------

I will be 85 somewhere in the mid 2050s. It seems like a mirage, an impossible
thing, but the future eventually arrives regardless of whatever you or I might
think about it. We all have a vision of what it is to be 85 today, informed by
our interactions with elder family members, if nothing else. People at that
age are greatly impacted by aging. They falter, their minds are often slowed.
They are physically weak, in need of aid. Perhaps that is why we find it hard
to put ourselves into that position; it isn't a pleasant topic to think about.
Four decades out into the future may as well be a science fiction novel, a far
away land, a tale told to children, for all the influence it has on our
present considerations. There is no weight to it.

When I am 85, there have been next to no senescent cells in my body for going
on thirty years. I bear only a small fraction of the inflammatory burden of
older people of past generations. I paid for the products of companies
descended from Oisin Biotechnologies and Unity Biotechnology, every few years
wiping away the accumulation of senescent cells, each new approach more
effective than the last. Eventually, I took one of the permanent gene therapy
options, made possible by biochemical discrimination between short-term
beneficial senescence and long-term harmful senescence, and then there was
little need for ongoing treatments. Artificial DNA machinery floats in every
cell, a backup for the normal mechanisms of apoptosis, triggered by lingering
senescence.

When I am 85, the senolytic DNA machinery are far from the only addition to my
cells. I underwent a half dozen gene therapies over the years. I picked the
most useful of the many more that were available, starting once the price fell
into the affordable-but-painful range, after the initial frenzy of high-cost
treatments subsided into business as usual. My cholesterol transport system is
enhanced to attack atherosclerotic lesions, my muscle maintenance and
neurogenesis operate at levels far above what was once a normal range for my
age, and my mitochondria are both enhanced in operation and well-protected
against damage by additional copies of mitochondrial genes backed up elsewhere
in the cell. Some of these additions were rendered moot by later advances in
medicine, but they get the job done.

When I am 85, my thymus is as active as that of a 10-year-old child. Gene and
cell therapies were applied over the past few decades, and as a result my
immune system is well gardened, in good shape. A combination of replacement
hematopoietic stem cells, applied once a decade, the enhanced thymus, and
periodic targeted destruction of problem immune cells keeps at bay most of the
age-related decline in immune function, most of the growth in inflammation.
The downside is that age-related autoimmunity has now become a whole lot more
complex when it does occur, but even that can be dealt with by destroying and
recreating the immune system. By the 2030s this was a day-long procedure with
little accompanying risk, and the price fell thereafter.

When I am 85, atherosclerosis is curable, preventable, and reversable, and
that has been the case for a few decades. There are five or six different
viable approaches in the marketplace, all of which basically work. I used
several of their predecessors back in the day, as well. Most people in the
wealthier parts of the world have arteries nearly free from the buildup of fat
and calcification. Cardiovascular disease with age now has a very different
character, focused more failure of tissue maintenance and muscle strength and
the remaining small portions of hypertension that are still problematic for
some individuals. But that too can be effectively postponed through a variety
of regenerative therapies.

When I am 85, there is an insignificant level of cross-linking in most of my
tissues, as was the case since my early 60s. My skin has the old-young look of
someone who went a fair way down the path before being rescued. Not that I
care much about that - I'm much more interested in the state of my blood
vessels, the degree to which they are stiff and dysfunctional. That is why
removal of cross-links is valuable. That is the reason to keep on taking the
yearly treatments of cross-link breakers, or undergo one of the permanent gene
therapies to have your cells produce protective enzymes as needed.

When I am 85, I have a three decade patchwork history of treatments to
partially clear this form of amyloid or that component of lipofuscin. Modified
enzymes are delivered here, a gene therapy applied there. I will not suffer
Alzheimer's disease. I will not suffer any of the common forms of amyloidosis
that degrade heart muscle performance or disrupt function in other organs. The
potential for such conditions is controlled, shut down with the removal of the
protein aggregates that cause cellular dysfunction. There is such a breadth of
molecular waste, however: while the important ones are addressed, plenty more
remain. This is one of the continuing serious impacts to the health of older
individuals, and a highly active area of research and development.

When I am 85, I am the experienced veteran of several potentially serious
incidences of cancer, all of which were identified early and eradicated by a
targeted therapy that produced minimal side-effects. The therapies evolve
rapidly over the years: a bewildering range of hyper-efficient
immunotherapies, as well as treatments that sabotage telomere lengthening or
other commonalities shared by all cancer cells. They were outpatient
procedures, simple and quick, with a few follow-up visits, so routine that
they obscured the point that I would be dead several times over without them.
The individual rejuvenation technologies I availed myself of over the years
were narrowly focused, not perfect, and not available as early as I would have
liked. Cancer is an inevitable side-effect of decades of a mix of greater
tissue maintenance and unrepaired damage.

Do we know today what the state of health of a well-kept 85-year-old will be
in the 2050s? No. It is next to impossible to say how the differences noted
above will perform in the real world. They are all on the near horizon,
however. The major causes of age-related death today will be largely
controlled and cured in the 2050s, at least for those in wealthier regions. If
you are in your 40s today, and fortunate enough to live in one of those
wealthier region, then it is a given that you will not die from Alzheimer's
disease. You will not suffer from other common age-related amyloidosis
conditions. Atherosclerosis will be reliably controlled before it might kill
you. Inflammatory conditions of aging will be a shadow of what they once were,
because of senolytic therapies presently under development. Your immune system
will be restored and bolstered. The stem cells in at least your bone marrow
and muscles will be periodically augmented. The cross-links that cause
stiffening of tissues will be removed. Scores of other issues in aging
process, both large and small, will have useful solutions available in the
broader medical marketplace. We will all live longer and in better health as a
result, but no-one will be able to say for just how long until this all is
tried.

~~~
maxander
Fingers crossed! Certainly much more will be known about human biology and the
mechanics of aging by then, given that what we know currently is mostly so
recent (it's instructive to remember that the two of the guys remembered for
discovering the nature of DNA, Watson and Crick, are still alive, and the
latter is still an active researcher [1]. Molecular biology is _that_ new.)

 _But_ \- all your examples suppose not only advances in biomedical science,
but also medical care aimed at correcting each of these problems. It adds up
to a _lot_ of drugs, therapies, or other interventions. In today's system, a
well-off and health-conscious individual would receive that level of care as a
matter of course- but today's system is a sprawling and highly dysfunctional
apparatus already, and I don't feel entirely confident about how it will
change in the face of future economic upheavals, political madness, climate-
change-fueled social instability, etc etc etc.

The lifespan of humans is increasing, but the lifespan of social
infrastructure such a the medical industry may be decreasing... which is
especially problematic since the former depends on the latter.

[1] Rosalind Franklin, sadly, died of ovarian cancer at the young age of 37.

~~~
glormph
Nitpick: Watson is still alive, but Francis Crick is most certainly not here
anymore.

~~~
maxander
Ack! Serves me right for googling without thinking. I suppose I saw the
figures for a different Crick.

------
reasonattlm
Want to help the elderly? Then help with the logistics needed to get current
first generation well-characterized senolytic drugs into widespread use. The
failing health of the elderly is the root of every challenge related to old
age, and that failing health is driven by the fundamental causes of aging such
as accumulation of senescent cells. To the degree that rejuvenation can be
achieved with reliability and low cost, such as through these senolytic drugs,
it should be a priority.

The dasatinib + quercetin combination for clearance of senescent cells is an
excellent candidate on the basis of cost, evidence, and amount of information
on these compounds, as well as a clear, low-cost, legal path for companies to
bring it to patients. The eventual size of the market is every human being
much over the age of 50.

1) Senescent cell accumulation is one of the root causes of aging, supported
by decades of scientific evidence [1]. In lab mice, removal of senescent cells
has partially reversed progression of osteoarthritis, lung disease, kidney
disease, tauopathies such as Alzheimer’s disease, and a long and growing list
of other age-related conditions.

2) A single treatment of dasatinib + quercetin clears a fraction of senescent
cells in aged mice, leading to lasting improvement in health as a result [2].
Monthly treatment of dasatinib + quercetin starting in late old age reverses
measures of age-related decline and extends life by 36% in mice [3].

3) Dasatinib is a generic chemotherapy drug, originally approved for the
treatment of cancer in 2006 as Sprycel. Pharmacology and side-effects in
humans are well characterized [4]. Quercetin is a widely used flavonoid
supplement. Quercetin is not effective versus senescent cells when used on its
own [5].

4) The non-profit Betterhumans is running human trials of dasatinib +
quercetin, as is the Kogod Center at the Mayo Clinic.

5) Dasatinib costs less than US$100 per dose if obtained from manufacturers,
deriving a human dose from the mouse studies. Perhaps US$200 per dose in the
form of Sprycel via the pharmaceutical market. Quercetin costs less than a
dollar per dose.

6) A drug approved by the FDA for one use can be prescribed by physicians for
other uses, if in their professional judgment it is safe and effective. This
is known as off-label use, and is commonplace for many medications.

[1]:
[https://doi.org/10.1111/j.1749-6632.2002.tb02115.x](https://doi.org/10.1111/j.1749-6632.2002.tb02115.x)

[2]: [https://doi.org/10.1111/acel.12344](https://doi.org/10.1111/acel.12344)

[3]:
[https://doi.org/10.1038/s41591-018-0092-9](https://doi.org/10.1038/s41591-018-0092-9)

[4]:
[https://doi.org/10.1124/dmd.107.018267](https://doi.org/10.1124/dmd.107.018267)

[5]:
[https://doi.org/10.1371/journal.pone.0190374](https://doi.org/10.1371/journal.pone.0190374)

~~~
fjsolwmv
How many doses does a person need per year?

What does "partially reversed" mean?

What are the side effects?

~~~
reasonattlm
Arguably one dose per year. Arguably several in close sequence, but still very
intermittently, such as once a year. Senescent cells accumulate slowly, so
there is no reason to dose frequently on an ongoing basis. Different mouse
studies of dasatinib + quercetin used single doses or a few monthly doses in
sequence. This is true of dasatinib, but varies for other chemotherapeutic
senolytics. Bcl-2 inhibitor chemotherapeutics generally want a week or a few
weeks of dosing, rather than a single dose, which is a compelling reason to
avoid them until better versions come along. The FOXO4-DRI injected peptide
was a single treatment of three doses over a week in mice. That again is
probably once a year in humans until someone turns up with evidence to suggest
otherwise.

Validation of the above educated guess, and some form of dose optimization,
will arrive sometime after the introduction of good senescence assays that
don't involve staining tissue samples, something that isn't viable for
everyday human medicine.

As to what "partially reversed" means, the answer is "read the literature". It
is all out there. Search PubMed for "senolytic". Use Sci-Hub to read papers.
The comparison pictures of treated and untreated mice in papers that have them
are particularly telling, but no substitute for the raw data on arthritis,
cardiovascular function, inflammation, neural function, tissue elasticity,
etc.

For side effects, a single dose dasatinib pharmacokinetics study in volunteers
with lots of references to start you off:
[https://doi.org/10.1124/dmd.107.018267](https://doi.org/10.1124/dmd.107.018267)

