organisms’ lifespans are determined by their genes & environment. we can modify our environment (diet, exercise, sleep, etc). we can modify gene activities w drugs/vitamins or possibly w CRISPR but we 1st have to understand the process of aging itself to know what to target. /1
the gene set any organism has was selected for in evolution. parents who produce lots of reproductively successful offspring pass on their genes. the selections for these genes took place over evolutionary time in conditions that were different from current conditions. /2
most animals achieve reproductive capability early & don’t live much longer than they can reproduce. why? bc the brain, liver, musculature, etc are there to present males to females & help us care for young til they are reproductively capable.

this is the way biology works. /3
men & women achieve reproductive capacity in our 2nd decade. women end their reproductive capacity in middle age w decades of lifespan remaining. why? bc over evolutionary time, moms devoted essential inputs to the likelihood of reproductive success of their kids. /4
this explains why women outlive their ovarian functions by decades. /5
men don’t typically live as long as women & though sexual functions decline, they can produce (some) viable sperm into their dotage. male functions, um, peter out over time. /6
though dads can invest time to kids’ reproductive success, over evolutionary time, we were apparently pretty dispensable after fertilization (or maybe birth). thus, our gene set doesn’t permit our brains, liver, musculature etc to outlive our testes. /7
if human evolution remains selective for millennia under conditions in which having great grandparents promotes greater reproductive success for kids, then our gene set might produce variants that extend human lifespan. /8
greenland sharks have a gene set & environment that permits them to live 400 yrs. for reasons we don’t understand, they don’t have babies til they are over 100. they can also eat pretty much anything they want. /9
i’d be v confident that sharks remain good swimmers & good maters for their whole lives. those are the traits that have been selected over evolutionary time. /10
we’ll not be able to swap 1 shark enzyme into ppl to give us shark longevity. we do need to optimize our environments to keep our brains & liver working well, do what we can to maintain muscle mass/functions, etc. we do have vaccines & public health measures that ⬆️ lifespan. /11
maybe there are approaches to help ppl’s genes work better in every tissue well beyond our historical reproductive capacity. hard problem but my best idea is targeting repair/resiliency pathways.

we’re working w evolutionary forces if interventions promote motility, repair, /12
infection resistance & frankly sex appeal. of these, the ability to repair cuts & bruises might be the easiest to assay in aging populations. don’t get snowed by ppl who say they’ve solved aging or reversed their aging. demand functional tests & keep working! /end

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More from @CharlesMBrenner

4 Oct
Living things maintain their order by taking in fuel to run chemical reactions. the fuels are protein, fat & carbohydrate. in common parlance, we burn these fuels to generate ATP that runs chemical reactions, to make everything in our bodies, repair everything, move & think. /1
Fully oxidized, the carbon in the fuels is exhaled as CO2. /2

The energy in the fuels consists of high energy electrons, whose energy is derived from the sun (that lesson for another day). /3
The difference between living things & locomotive machines that imparts the ability to build ourselves is that we have NAD coenzymes that capture the energy associated with fuel oxidation in a nearly lossless manner. /4
Read 8 tweets
29 Aug
Defining age reversal via a score on an aging clock rather than a functional measurement would constitute the single biggest scam in the entire tawdry history of anti-aging scams. let me explain /1
There's a buyer for the promise of anti-aging of course. this person wants to maintain functions for a longer period of time. maybe they run 7 min miles with their grandson, maybe they play competitive chess, maybe they skateboard and need to be able to recover from scrapes /2
Those are functional metrics: running, playing chess, wound repair. in all of animal history, every animal has declined in its motility, mental ability and repair capacity after it reaches some level of maturity. people want to prolong their mastery or better: reverse aging /3
Read 12 tweets
22 Aug
Valproate is a potentially dangerous drug used for ppl with seizures. Abbott was penalized $1.6 billion for off-label marketing this drug in nursing homes as a sedative /1…
The data in the paper David cites do not show that valproate restores swimming ability of fish--fig. 1D shows that most low dose valproate-treated fish swim WORSE than control. High dose was clearly much worse /2…
The SIRT1 western blots in Fig. 4 are some of the worst I've ever seen published. With respect to swimming, rather than look at dozens of fish as they did in Fig. 1 (already a fishy result), they decided to look at only 3 fish with valproate + EX527 /3…
Read 5 tweets
19 Aug
I'll defend model organisms. However, the proposal that something is conserved for longevity needs to be specifically examined. It's time to explain something about yeast that ppl haven't thought about enough and yes, this concerns SIR2 /1
there are two assays one can use to analyze lifespan in yeast. The 1st one is called chronological lifespan. It's simple. Grow a culture of yeast and see how long the cells are viable to form a colony. Chronological lifespan is measured in days or weeks /2
it might surprise you that sir2 DELETION lives longer in this assay. the work was done by Valter Longo and was published in Cell… ... let that result sink in a minute /3
Read 20 tweets
13 Aug
scicomms is very important. if we are making progress on matters related to human health, we should do our best to explain the developments to the general public. however, it must be remembered that the entirety of human history has been marked by false & exploitative claims /1
with respect to longevity. plants & their extracts have always been claimed to have essentially magical properties of age reversal. extraordinary claims require extraordinary proof. journals have repeatedly failed us & have legitimized overblown claims, exciting- /2
sounding mechanisms & nonreproducible results that were heavily biased by models, expectations & the subsequent exploitation of the resulting stories. the longevity field has assuredly been fouled by this stuff. publication & defense of bad science undermines real progress. /3
Read 9 tweets
13 Aug
The Gross Clinic by Thomas Eakins is one of the most important paintings from the 19th century & the history of medicine. It depicts Samuel Gross, teaching surgery to Jefferson Medical College students prior to the use of white coats /1
The black suits were what the students and Gross wore outside on the dirty streets of Philadelphia. Gross gesticulates with a bloody scalpel. The patient’s mother cannot bear to watch /2
This painting was owned by Jefferson and on display in Jefferson Alumni Hall when I was an assistant prof—it was subsequently sold & is on display at the Philadelphia Museum of Art. It is breathtaking.
Read 4 tweets

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