Update: PDF of the paper: https://rejuvenomicslab.com/wp-content/uploads/2022/01/expger02_evolution_aging.pdf
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The authors also found little evidence of aging in multiple chelonian species, in some salamanders and in the tuatara. Protective adaptations and life history strategies – like bony shells and a relatively slow pace of life, in the case of turtles – help to explain the negligible aging in these long-lived species. In another study, Rita da Silva and colleagues examined mortality rate changes with age in captive animals, focusing on 52 turtle, terrapin, and tortoise species in zoo populations. Similarly, da Silva et al. found that senescence was slow or negligible in roughly 75% of the species evaluated. Moreover, roughly 80% experienced aging rates lower than that of modern humans. Unlike humans and other species, the findings in controlled settings also suggest that some turtle and tortoise species may reduce physical aging in response to better environmental conditions, in which – as conditions improve – they can allocate more energy to survival rather than protection, thereby extending their lifespans.
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Warning: Experimental rant
From this paper linked above, it may look like aging is an evolutionary strategy for the underdog (NOT saying here that this is the demonstration of the paper’s author): mammals could not compete with dinosaurs, so they evolved to age rapidly and so to live and change more intensely, and thus to adapt more rapidly and efficiently as a species.
But as the species comes to dominate, aging capabilities come back. For example, the first elephants were smaller, as most mammals, but have since then, as they became dominant in their biotope, develop up to six sets of molars, which is clearly a sign of better longevity (elephants need their molars to eat and thus to survive).
Now, evolution seems to be excruciatingly slow for a short-lived species such as ours. And I would argue that it is “natural” that humans proceed to accelerate it using their unique cerebral capacities. In this sense, doing intensive scientific research openly targeting longevity, even in orders of magnitude, fits very well with evolution itself.
I find this idea somehow comforting 
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I found this really interesting. Perhaps the future of gene therapy is insertion of additional copies of key cancer supression genes, to make us more like turtles.
Long-Lived Turtles are Highly Resistant to Cancer
The most interesting comparative biology programs aim to use the cellular biochemistry of unusually regenerative, long-lived, and cancer resistant species as a tool to better understand our vulnerabilities to aging and injury. In principle, understanding why a species is unusually long-lived could point to a basis for therapies to slow aging in humans, while understanding why species such as naked mole-rats, elephants, whales, and turtles have such low incidence rates of cancer could point to ways to shut down human cancers. This remains a hypothesis, as comparative biology research has not yet advanced to the point at which technology demonstrations of transferring biochemistry between species are commonplace, or at which any of the discoveries seem easily used as a basis for the development of therapies. It may just be a matter of time, or it may be that this is a project for a more distant future in which engineering significant changes in human biochemistry is an easier undertaking.
Turtles occupy the extremes of biology, but perhaps are best known for their longevity: even the shortest-lived species (the chicken turtle, Deirochelys reticularia) exceed 20 years, whereas others, such as Galapagos and Aldabra giant tortoises, can live well over 150 years. Turtles also exhibit remarkable variation in adult body size. Theoretically, organisms with more cells and higher lifetime cellular turnover should face greater cancer risk. Therefore, large, long-lived species must have evolved mechanisms to mitigate this increased risk. On the basis of their considerable variation in both body mass and lifespan, turtles are a promising group for studying the evolution of natural cancer resistance. However, cancer reports in turtles remain exceedingly rare - far less common than in mammals, birds, or even other reptiles.
To build on previous studies, we analyzed 290 additional necropsies from 64 turtle species across eight zoos in Europe, the United Kingdom, and the United States, representing nine taxonomic families. Despite extensive taxonomic and geographic coverage - from the tiny black-breasted leaf turtle (Geoemyda spengleri; 150 grams) to the Galapagos giant tortoise (Chelonoidis spp.; less than 300 kilograms) - we found only one case of neoplasia, in the mata mata (Chelus fimbriata), with no malignancies detected. This corresponds to neoplasia and cancer prevalence estimates of 0.34% and 0%, respectively. These values are similar to those reported by other groups. Taken together, this data reinforces the conclusion that cancer is very uncommon in turtles. When cancer does occur, it rarely metastasizes, suggesting that turtles may possess biological or evolutionary traits contributing to their low cancer prevalence.
Genomic analyses of large, long-lived species such as Galapagos and Aldabra giant tortoises, have revealed positive selection and duplications in key tumor suppressor genes, metabolic regulators, immune response genes, and pathways involved in genome maintenance. Moreover, comparative studies indicate that Galapagos tortoises exhibit enriched expression of tumor suppressors, proteostasis regulators, and metabolic pathways associated with growth control, potentially contributing to their reduced cancer susceptibility. Functional assays in Galapagos giant tortoise cell lines further suggest an enhanced ability to trigger apoptosis to mitigate endoplasmic reticulum stress, which may help clear damaged cells before tumorigenesis can occur.
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The Key Cancer Supressor Genes Identified So Far
From ChatGPT:
In humans, several tumor suppressor genes play a central role in suppressing cancer by regulating cell growth, repairing DNA damage, and controlling apoptosis. The “top” cancer suppression genes are those most frequently mutated, deleted, or silenced across many cancers and best validated in research. Here are the major ones:
1. TP53 (p53)
- Often called the “guardian of the genome”.
- Functions: DNA repair, cell cycle arrest, apoptosis, and senescence in response to stress.
- Mutated in >50% of all human cancers, making it the single most frequently altered tumor suppressor.
2. RB1 (Retinoblastoma protein)
- Regulates the G1/S checkpoint of the cell cycle.
- Loss of RB1 leads to uncontrolled cell division.
- First identified in retinoblastoma, but also altered in lung, breast, and other cancers.
3. PTEN
- Negative regulator of the PI3K/AKT signaling pathway.
- Loss of PTEN leads to increased survival, growth, and metabolic activity of cancer cells.
- Commonly mutated or deleted in prostate, endometrial, and brain cancers.
4. BRCA1 and BRCA2
- Key roles in homologous recombination–mediated DNA double-strand break repair.
- Mutations predispose to breast, ovarian, prostate, and pancreatic cancers.
- Carriers have high lifetime risk for certain cancers.
5. APC (Adenomatous Polyposis Coli)
- Negative regulator of the Wnt/β-catenin pathway.
- Mutated in most colorectal cancers (especially familial adenomatous polyposis).
- Loss leads to aberrant intestinal cell proliferation.
6. VHL (Von Hippel–Lindau)
- Regulates hypoxia-inducible factors (HIFs).
- Mutations drive angiogenesis and tumor progression, especially in clear cell renal cell carcinoma.
7. CDKN2A (p16^INK4a and p14^ARF)
- Encodes two proteins that regulate RB1 and p53 pathways.
- Frequently inactivated in melanoma, pancreatic cancer, and gliomas.
8. NF1 and NF2 (Neurofibromin 1 & 2)
- NF1: RAS pathway regulator; loss causes neurofibromatosis type I and various cancers.
- NF2: Encodes merlin, a cytoskeletal protein suppressing growth factor signaling.
9. SMAD4 (DPC4)
- Central mediator of TGF-β signaling.
- Frequently mutated in pancreatic and colorectal cancers.
10. WT1 (Wilms’ Tumor 1)
- Plays roles in kidney development and tumor suppression.
- Mutations associated with Wilms’ tumor and some leukemias.
Honorable Mentions
- TSC1/TSC2 (regulate mTOR signaling; tuberous sclerosis complex tumors).
- FH & SDH (metabolic tumor suppressors linked to hereditary cancers).
- LKB1 (STK11) (mutated in Peutz–Jeghers syndrome and lung adenocarcinoma).
In summary:
The “big four” universal tumor suppressors are TP53, RB1, PTEN, and BRCA1/2.
Others (APC, VHL, CDKN2A, SMAD4) are critical in specific cancers.
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