Is aging an engineering problem

The short answer is yes. 

If you are reading this newsletter, you probably already knew the answer. You also know the answer to this:  

Is aging mutable? 

Yes, and most of us don't have to look far for evidence.

Now, back to the subject at hand.

The word "impossible" should be used with care. It frequently has to be retracted. Yet, throughout history, which has had its share of tireless defeatists, it is (somewhat) unusual for pessimism to override all available evidence.

One exception is how the public thinks of aging.

Many people feel there is an unchallengeable law, as unforgiving as gravity, that limits our healthy years. In their minds, our bodies just "wear out."

If this was true, all animals should have similar lifespans, and all should age at about the same rate.

But this isn't the case. 

So, why do mice live for 1 to 3 years, while their similarly sized subterranean cousin, the naked mole rat, lives for 32?

Variation in lifespans between species, including closely related ones (like ravens and crows, or otherwise identical types of salmon), suggests aging is largely a programmed process. This doesn't mean our bodies are indistinguishable from software, just that parts of our biology are reprogrammable.

If we merely “wore out,” parabiosis shouldn't work (Conboy, 2005; Eggel, 2014). Yet, again and again, young blood rejuvenates old mice (and old blood ages young ones). Modifying one or two genes should not double the lifespans of any animals. It certainly shouldn't show a ten-fold increase, yet this is what we've seen with C. elegans (Shmookler, 2009.

And gene therapy, delivered with our patent pending CMV vector, shouldn't extend the lifespans of mice by over 40% (Jaijyan, 2022).

Yet it did. 

We (subtly) reprogram ourselves with our lifestyle decisions. In the near future, we'll do it precisely and sustainably with gene therapy. 

Others claim our lifespans are limited by genetic "tradeoffs." 

In other words, genes that help when we're young suddenly betray us once our reproductive years are behind us. The examples given to support widespread “antagonistic pleiotropy” in the context of biological aging are rather unconvincing (Goldsmith, 2006). However, one example that warrants scrutiny is the alleged tradeoff between aging and cancer. 

Cellular senescence is an important protective mechanism against cancer, but it's one of many. Extrapolating so much from a single process feels a bit forced anyway.

Moreover, if such a tradeoff existed, we'd find higher rates of cancer among long-lived mammals when, in fact, the opposite is true. Mice and other small mammals are notoriously prone to cancer - the exact reasons for which are still being investigated (Katzourakis, 2014). On the other hand, long-lived mammals like whales and elephants have evolved effective tumor suppressing mechanisms (Caulin, 2011).

In other words, nature already has a vast array of protective and regenerative mechanisms we can tap into with gene therapy. 

Wait.

You might object: everyone knows larger species tend to live longer than smaller ones! 

Ok, fair enough.

But, except for the bicentenarian Bowhead, whales live about as long as we do (Seim, 2014). Moreover, a single case of cancer has never been observed in the naked mole rat of East Africa, which is long-lived, tiny, and a mammal. 

Of course, you don't have to sail to the middle of the ocean or safari across Kenya to find evidence for the programmed nature of biological aging. 

What about your backyard (or, let's say, about a hundred miles from it in any direction)?  

In California you might see Redwoods that have seen millennia come and go. In Maine you'll encounter lobsters, which can live well over 100 years and don't become frail.

Trees and crustaceans might seem far removed from us, but what if you live in a city?

Aside from pigeons and squirrels, you can just look at other people.

You don't have to find a progeria patient to see that, due to genetics and lifestyle, people - yes, your fellow Homo sapiens - age at wildly different rates. 

Some folks prefer to bury their heads in the sand and aimlessly cast stones. When this happens, we have to remember Galileo's words:

E pur si muove. 

And yet it moves.

The earth moves around the sun and biological aging is open to intervention.

References and Suggested Reading

Caulin, Aleah F., and Carlo C. Maley. "Peto's Paradox: evolution's prescription for cancer prevention." Trends in ecology & evolution 26.4 (2011): 175-182.

Conboy, Irina M., et al. "Rejuvenation of aged progenitor cells by exposure to a young systemic environment." Nature 433.7027 (2005): 760-764.

Goldsmith, Theodore C. The Evolution of Aging: How new theories will change the future of medicine. Azinet, 2006.

Goldsmith, Theodore C. "On the programmed/non-programmed aging controversy." Biochemistry (Moscow) 77.7 (2012): 729-732.

Eggel, Alexander, and Tony Wyss-Coray. "A revival of parabiosis in biomedical research." Swiss medical weekly 5 (2014).

Jaijyan, Dabbu Kumar, et al. "New intranasal and injectable gene therapy for healthy life extension." Proceedings of the National Academy of Sciences 119.20 (2022): e2121499119.

Katzourakis, Aris, et al. "Larger mammalian body size leads to lower retroviral activity." PLoS pathogens 10.7 (2014): e1004214.

Kenyon, Cynthia, et al. "A C. elegans mutant that lives twice as long as wild type." Nature 366.6454 (1993): 461-464.

Seim, Inge, et al. "The transcriptome of the bowhead whale Balaena mysticetus reveals adaptations of the longest-lived mammal." Aging (Albany NY) 6.10 (2014): 879.

Shmookler Reis RJ, Bharill P, Tazearslan C, Ayyadevara S. Extreme-longevity mutations orchestrate silencing of multiple signaling pathways. Biochim Biophys Acta. 2009 Oct;1790(10):1075-83. doi: 10.1016/j.bbagen.2009.05.011. Epub 2009 May 22. PMID: 19465083; PMCID: PMC2885961.