Thread by @CharlesMBrenner

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