Andrei Seluanov’s DoNotAge Conference 2026 lecture focused on a part of the genome that is easy to overlook in longevity discussions: LINE-1 retrotransposons and their possible contribution to age-related inflammation.
What is LINE-1?
LINE-1, or L1, is a family of transposable elements distributed throughout mammalian genomes. Most copies are inactive, but some retain machinery needed for reverse transcription and retrotransposition. Ageing research has increasingly examined whether loss of genomic repression allows LINE-1 activity to contribute to DNA damage and inflammatory signalling.
The SIRT6 connection
A 2019 Cell Metabolism paper coauthored by Seluanov and Vera Gorbunova reported increased LINE-1 activity and cytoplasmic LINE-1 cDNA in SIRT6-deficient mice and naturally aged wild-type mice. In the SIRT6-deficient model, the cytoplasmic DNA activated cGAS-associated type-I interferon signalling. Reverse-transcriptase inhibitors reduced inflammatory signalling and DNA-damage markers and improved health and lifespan in the SIRT6-knockout mice.
The model matters: extending survival in a severely SIRT6-deficient mouse is not the same as demonstrating an anti-ageing therapy in healthy humans.
Why cGAS is more complicated than simply blocking inflammation
A 2026 Nature Aging paper from the Rochester group adds a major mechanistic complication. Rather than being uniformly harmful, cGAS also appears to have a nuclear role in maintaining chromatin organization and suppressing LINE-1 transcription. Mice lacking cGAS showed increased LINE-1 expression, higher inflammation and DNA-damage signalling, greater frailty and a shortened median lifespan.
The biology therefore cannot be reduced to “cGAS causes inflammaging, so blocking cGAS must slow ageing.” The pathway has context-dependent functions.
Other 2025–2026 LINE-1 evidence
Separate mouse research published in Nature Aging in 2025 found that LINE-1 activation contributed to cardiac ageing through cGAS–STING signalling and that experimental inhibition of LINE-1 reverse transcription or STING improved several cardiac-ageing phenotypes in old mice. This was not the Seluanov conference study, but it strengthens the broader biological case that LINE-1 activity can participate in age-related pathology.
What the conference added
The conference lecture discussed LINE-1 as part of the “dark genome,” its relationship to inflammaging, SIRT6-mediated silencing and experimental suppression strategies. Additional intervention details should remain conference-stage unless they can be tied to a specific paper, registry or formal research record.
Human evidence?
None of the mouse findings above establish that reverse-transcriptase inhibitors, STING inhibitors or SIRT6-targeting supplements extend human lifespan. Existing antiretroviral drugs also have established clinical indications and safety considerations; they should not be repurposed as longevity interventions on the basis of animal experiments.
Sources
Official DoNotAge Conference 2026 highlights
Cell Metabolism (2019) — LINE-1 derepression in aged and SIRT6-deficient mice
Nature Aging (2026) — cGAS-deficient mice, LINE-1 and premature ageing
Nature Aging (2025) — LINE-1 activation and cardiac ageing
DoNotAge Conference 2026 lecture video
Return to the 2026 conference hub.
Linked entities and research
DoNotAge Conference 2026
DoNotAge Conference 2026 was held in London on September 26–27, 2026. The official highlights archive presents 12 2026 conversations spanning human trials, DNA repair, inflammation, muscle and exercise, replication and research funding, plus a 2025 conference recap.
2026 Conference Lecture — Inflammaging, LINE-1 & the Dark Genome
The conference lecture discusses LINE-1 activity, inflammaging, SIRT6 repression of transposable elements and preclinical approaches to LINE-1-associated inflammatory signalling.
Andrei Seluanov
Speaker at DoNotAge Conference 2026.
Vera Gorbunova
Speaker at DoNotAge Conference 2026.