DNA repair is the secret to a long life: bowhead whale repair proteins are already in human trials
Research shows that in nearly half of hospitalised COVID-19 patients, dormant viruses in the body were reactivated, with higher inflammation and cell damage a year later; and what long-lived animals like the bowhead whale have in common is not tumour-suppressor genes but stronger DNA repair — drugs for it are already in human trials.
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Some viruses are never cleared, only held down
Over a lifetime a person is infected by a great many viruses, but as long as the immune system is healthy, most infections are defeated. Some pathogens, however, are never fully cleared — they quietly lie dormant in the body, held in check by a healthy immune system. Once immunity is weakened, they resurface; many of the complications seen in people with HIV, for instance, are caused by reactivation of dormant viruses. Researchers therefore wondered: could a severe infection like COVID-19 also weaken the immune system and wake dormant viruses, becoming a source of long COVID? This hypothesis determines what has to be tested next.
— CharmaniNearly half of hospitalised patients had old viruses revive, but causation is unsettled
The team looked back at COVID-19 patients hospitalised in 2020 and 2021, testing blood samples, nasal swabs and lung fluid for reactivation of common viruses. Nearly half showed viral reactivation. After a year of follow-up, these people had higher inflammation levels, stronger immune-cell activity and more cell damage. But the study did not directly diagnose long COVID, and it is only correlational: COVID-19 may induce stress that triggers reactivation, and reactivation may then amplify the inflammation COVID-19 caused, forming a loop; or reactivation may simply be another symptom of immune exhaustion rather than a cause of long COVID. A phase 2 clinical trial is testing antivirals against herpesviruses, on the reasoning that if the reactivated viruses are themselves harmful, the therapeutic target should shift to those reactivated viruses.
— CharmaniDNA damage is not just carcinogenic — it is upstream of ageing
DNA damage can mean a change in a base pair (A, C, G, T), or a change in the chemical structure of the base itself, such as the addition of an oxygen atom. It is not only the cancer-causing mutation people worry about. DNA damage is strongly correlated with ageing and is thought to underlie hallmarks of ageing such as inflammation, cellular senescence and mitochondrial dysfunction. Conversely, long-lived animals such as naked mole-rats and bowhead whales tend to have outstanding DNA repair capacity; bowhead whales live past 200 years and rarely get cancer. So researchers wondered: can we transplant their repair mechanisms to extend human healthspan?
— CharmaniThe repair protein works when moved into human cells and fruit flies too
Last year the podcast reported a clue from the bowhead whale: a protein called cold-inducible RNA-binding protein (CIRBP), linked to extremely strong repair of DNA double-strand breaks. Double-strand breaks are the most destructive form of DNA damage. The bowhead whale's rare cancer seems to stem mainly not from the usual tumour-suppressor genes but from this repair capacity. More importantly, putting the protein into human cells and fruit flies works just as well, showing it does not depend on the whale's special environment. The question thus shifts from ‘why do they live long’ to ‘can we transplant this mechanism’ — and that is the most tantalising part.
— CharmaniBoosting only one repair system can sometimes make things worse
It is far from that simple. Enhancing human DNA repair is an old problem, and the difficulty is that there are too many systems: about six major repair systems, which interact, overlap, and sometimes one system needs the product of another. When only one of them was boosted in the past, the effects seen were very limited, and sometimes it made things worse. So you cannot simply say ‘just switch the repair genes on’. We are still at the stage of figuring out how these species work, and of trying experiments in petri dishes.
— CharmaniThe hope for longer life is in human trials, not supplements on the shelf
The same team moved from bowhead whales to rodents: beavers can live 10 to 12 years, while mice may live only a few. They found that overexpression of an enzyme called Sirt6 is linked to longer species lifespan; human centenarians may also carry favourable variants of Sirt6. More practically, Fucoidan, a compound naturally present in brown algae, can activate Sirt6 and is already being treated as a potential therapeutic. A study is now giving Fucoidan to men aged 50 to 80 to observe the effects. But the researchers also caution: there is a lot of hype around NAD+-related supplements on the market, and not much evidence. The hope exists, but it needs to be verified in human trials, not cashed in by supplements.
— CharmaniIn their own words · checked verbatim
It's often these.Dorant viruses.Resurfacing that cause a lot of other problems.So there was this idea.Maybe is there some link here with COVID 19 with long COVID
Charmani1:37
And what they found is that.Nearly half of those people.Had a reactivation of con viruses.In their body.
Charmani1:37
But if these reactivating viruses are causing their own problems inherently.Then maybe instead of.Treating Covid-19.By.Targeting Sas Covy too.Maybe we should be treating Covid 19 with.Antivirals.For other things.
Charmani1:37
So certain species have these.Mechanisms that we don't have.And then I guess the question is, can we borrow them and stick them in our own So somehow, That is the tantalizing, tantalizing hope.
Charmani8:22
and when researchers have boosted one, they've seen very limited effects and sometimes they've even made things worse so it's not as easy as just been like okay let's just boost these and they're a away we go
Charmani8:22
there's a lot of hypere around supplements that try to raise this molecule's levels.But there's not a lot of evidence they actually.Work
Charmani10:59
Figures
| Share of hospitalised COVID-19 patients with viral reactivation | nearly half | 1:37 |
| Bowhead whale lifespan | over 200 years | 8:22 |
| Beaver lifespan | 10-12 years | 10:59 |
| Fucoidan human trial participants | men aged 50-80 | 10:59 |
| Number of major human DNA repair systems | about 6 | 8:22 |
| Clinical trial phase targeting reactivated viruses | phase 2 | 1:37 |
Glossary
- dormant virus
- A virus not fully cleared after initial infection, held in check by the immune system, which can reactivate when immunity weakens.
- double-strand break
- A break in both strands of DNA at once, one of the most severe forms of DNA damage; failed repair can cause genomic instability.
- CIRBP (cold-inducible RNA-binding protein)
- A protein found in the bowhead whale, linked to enhanced repair of DNA double-strand breaks.
- Sirt6
- An enzyme linked to DNA repair, metabolism and lifespan; overexpression is seen in long-lived rodents and some centenarians.
- Fucoidan
- A natural compound in brown algae that can activate Sirt6 and is in human trials as a potential anti-ageing drug.
- NAD+
- A coenzyme involved in metabolism and DNA repair; related supplements are hyped but clinical evidence is limited.
How to listen
Researchers focused on the clinical mechanisms of long COVID, R&D staff and investors in anti-ageing drug companies, and general readers who want to tell scientific evidence apart from supplement marketing.
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