One good thing about riding the Octogenarian Express is that the passengers no longer have time for procrastination. Do It Now! becomes the inevitable motto, which is likely why Bill Killeen finally made it to Paris after lollygagging for sixty years. A little travel, of course, always makes one want more, but ancient bodies snort and grumble and start looking for their easy chairs. When we finally have the means and the enlightenment to do brilliant things, our backs go out, our sciatica acts up, our lungs cry for help, and on that murky horizon we can make out the figure of the Grim Reaper, rearing up on his steed. We know if he can nail Dolly he can run down anybody.
There are two alternatives: we can submit meekly because we don't believe in magic, or we can join the hunt for the Holy Grail, the legendary wonder which can suspend time, maybe even turn it back. Poppycock, you say, and with good reason. In all the history of mankind, no one has unearthed the secret, even Dick Clark. Whatever we do, our cells continue to age until they become defective. As time passes, normal metabolic stress, environmental factors and internal wear and tear cause progressive harm to our cells while the body's natural repair and cleanup systems grow less efficient. Eventually, the Reaper rides in, executes his Mandible Claw Hold and we're finished.
But what if our cells ceased to age? What if they could be reprogrammed by resetting the chemical marks on DNA and making cells young again? As we sit here today snuggling our coffee and watching Good Morning America, there are superheroes like David Sinclair hard at work trying to do just that. The science is called cellular epigenetic reprogramming, and the studies on its progress are encouraging.
David Sinclair, The Man With The Plan
The first thing scoffers should know about David Sinclair is that Harvard University, that bastion of no-nonsense, hired him. Harvard is not in the business of fooling around. Sinclair's early discoveries in genetics and molecular biology laid a foundation for subsequent work on sirtuins, epigenetics, NADs and the biology of aging. His 2023 study in Cell demonstrated that partial cellular reprogramming using modified Yamanaka factors can reset youthful gene expression and reverse aging in mice. Yamanaka factors are a group of four specific protein transcription factors that can reset a mature, specialized adult cell into an immature, versatile stem cell. Animal experiments successfully restored vision in old mice with glaucoma by rejuvenating damaged retina nerve cells. Good job, but mice are not humans, except for Mickey.
Currently, Life Biosciences, a company Sinclair co-founded, is running the first human trials as we write. Why use the eye? Because it's easily accessible so that therapies can be delivered locally and vision can be measured precisely. The first patient was dosed in June for open-angle glaucoma and sudden optic nerve stroke (NAION). Results are expected soon. Sinclair is also pushing a pill version---chemical programming to "epigenetically restore the animal and eventually the person." It would travel through the bloodstream. Some scientists are worried because the chemicals used are in very high concentrations. Then again, Sinclair IS tinkering with defeating Death so you can't just take an aspirin.
Should we be encouraged? Sure! This is the most serious attempt ever to reverse age-related loss of function and much more realistic than Serge Voronoff's grafting of sliced baboon testicles onto elderly men. If it works, it's enormous, so we're rooting from the cheap seats. Maybe we'll get to visit Northumberland after all.
Six Things You Don't Know About Longevity
1. Food plus exercise actually moves the clock consistently. A Yale review of 51 human studies found Mediterranean, low-carb or low-fat eating patterns and regular exercise consistently decreased epigenetic age across 16 different clocks. You thought so, but there was no proof. Now, reams of pooled evidence attest to the fact.
2. The greatest progress in longevity comes from existing drugs, not supplements. Metformin, semaglutide (Wegovy/Ozempic) and anti-TNF anti-inflammatory drugs each significantly decreased measured age across all 16 epigenetic clocks. Researchers acknowledge it may be because they fix underlying metabolic diseases, but it shows age markers are modifiable.
3. The APOE2 longevity gene works by fixing DNA. We knew APOE2 people live longer and avoid Alzheimer's, but new Buck Institute work shows how: APOE2 neurons strongly upregulate DNA repair pathways and carry significantly less DNA damage, and they resist becoming senescent after stress. Even adding APOE2 protein to APOE4 cells reduced damage, hinting at a future drug, not just genetics.
4. Aging flips your genes from long to short---and it's reversible. Your long genes (brain function, regulation) get quiet with age; short genes (inflammation, telomere stress) get loud. Seven interventions including rapamycin and resveratrol led to a relative increase in long gene transcripts.
5. It's not just your age, it's your speed. And now we can measure it. A 2026 Nature Ageing study tracked people over years; those whose epigenetic clocks speed up faster had significantly higher mortality. That means a simple blood test over time could tell if your diet and exercise changes are actually working months before you feel the results.
6. Better predictors than Horvath clocks now exist for function. New transcriptomic aging scores (TAGS) outperformed epigenetic clocks in predicting frailty, walking speed, cardiovascular disease and mortality. That's huge for you---it links molecular age directly to staying functioning, not just years.
Good News!
An AI drug candidate called Rentosertib which was originally developed by Insilico Medicine to target idiopathic pulmonary thrombosis reduced biological age by three or four years in a small clinical study. It is recognized as the world's first drug candidate where both the biological target and the molecular structure were discovered and designed entirely using generative AI. Rentosertib has advanced to Phase III clinical trials following positive Phase II results.
Rapamycin currently remains the single most reliable lifespan extender across sexes. Rapamycin extends lifespan by blocking a master growth switch called mTOR, which forces cells to shift from growth mode into a cleanup and repair state. When mTOR is active, cells grow and divide. When rapamycin blocks mTOR, cells start Autophagy, breaking down damaged proteins and recycling old parts. This internal housekeeping mimics known lifespan-extending benefits of caloric restriction without requiring you to eat less food. Slowing down constant cellular growth helps reduce the chronic low-grade inflammation that drives many age-related diseases.
The ABCs Of Dodging The Reaper
The Grim Reaper is like any other predator. He goes after the low-hanging fruit first, so climb further up that tree. Here in plain English is the Simple Plan for longevity:
Move a little, often. Walk 20-30 minutes in the morning before it gets hot. Twice a week, stand up and sit down from a chair 10 times. Leg strength is what keeps you out of a nursing home. Eat like those old Mediterranean guys. Not necessarily a specific diet but more olive oil, beans, fish, nuts, veggies. Eliminate or greatly reduce soda, white bread and processed meat. This practice is one of the few things that actually made people's aging clocks go backward.
Keep weight and blood sugar steady. The drug semaglutide made clocks younger because it fixes blood sugar and inflammation. You can get much of that effect without a drug by eschewing sugary drinks, eating smaller portions at dinner and walking after you eat.
Sleep at the same time every night, hopefully 7-8 hours. We know it's not easy for everyone. Keep the room dark, no TV. Melatonin is a safe supplement for most. Poor sleep ages you faster than almost anything.
Get out and meet people. Call a friend, go to a coffee shop or bookstore, see a Gator game, drop in at Heartwood or One Love Cafe or follow Vicki Bordeaux around. Statistics show that loneliness ages a person as much as smoking, which is scary. Talking to people is literally longevity medicine. We're trying to set up a lifeline where you can call Gina Hawkins directly, but she's not sold yet.
If you can't hear well, your brain works harder and shrinks. So what if you have to wear hearing aids, nobody cares. Keep your glasses updated. If you can't see, you fall. Forget the exotic supplements, they're expensive and they don't deliver as much as they promise. Centrum Silver is a good multivitamin, maybe throw in some extra Vitamin D. The big review of 51 studies found most anti-aging products did not lower aging clocks. Food, movement and sleep did.
Remember, you can now measure if what you're doing is working...there are blood tests which show your aging speed. If you're no longer working, think of putting the above recommendations to work as your new job. Good luck. Good Lord willin' and the creek don't rise, we'll see you soon in the sunny hills of Octogenaria-by-the-sea.
That's all folks....
bill.killeen094@gmail.com
