# The impact of LINE-1 retrotransposons on life span, SASP, and telomeres in vivo

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $334,308

## Abstract

DNA damage accumulates with age in somatic tissues where it contributes to their dysfunction by causing
mutations and cellular senescence. Senescent cells alter tissue microenvironment via secretion of
proinflammatory molecules. DNA damage from endogenous or exogenous sources alone or in combination
with defects in DNA repair pathways often decreases longevity. Long interspersed element-1, L1, an
endogenous retrotransposon, contributes to genomic instability via retrotransposition and the induction of DNA
double-strand breaks. Although endogenous L1 elements are expressed in normal human tissues and cause
DNA damage and cellular senescence, whether L1 affects mammalian life span in vivo is unknown. Among the
500,000 L1 copies present in mammalian genomes only a few L1 loci are capable of causing further DNA
damage. These L1 loci are often polymorphic for their presence in human genomes (pL1s) and are responsible
for the bulk of L1-induced DNA damage. Although some individuals contain two or three times as many of
these pL1 loci than others, the impact of this variation on human life span is not known. Our preliminary data
generated using a transgenic rat model support that a functional L1 transgene increases levels of
proinflammatory markers and shortens average and maximal lifespan in vivo. Our preliminary data also show
that L1 endonuclease cuts telomeric sequences in vitro and may do so in vivo. We hypothesize that
polymorphic L1 loci shorten mammalian lifespan in a dose-dependent manner by causing DNA damage that
induces proinflammatory markers and/or telomere attrition. We will test this hypothesis by using custom
transgenic rats to model variation in the number of functional L1s observed in the human population in order to
study the effect of this variation on longevity in vivo. We will also use DNA samples collected from average and
long-lived (>99 year old) individuals to determine their pL1 content and whether the number of pL1s per
genome correlates with life span. We will use in vitro and tissue culture approaches to determine whether L1
contribution to an increase in SASP markers or telomere attrition could be a plausible mechanism(s) by which
L1 may impact longevity. Combined our findings would provide a currently lacking experimental support for pL1
impact on longevity in vivo and novel mechanisms underlying this effect.

## Key facts

- **NIH application ID:** 9932265
- **Project number:** 5R01AG057597-03
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Victoria Perepelitsa Belancio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,308
- **Award type:** 5
- **Project period:** 2018-08-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932265

## Citation

> US National Institutes of Health, RePORTER application 9932265, The impact of LINE-1 retrotransposons on life span, SASP, and telomeres in vivo (5R01AG057597-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9932265. Licensed CC0.

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