Small plastic or metal bits at the end of shoelaces, known as aglets, prevent laces from unraveling and protect them from wear and tear. Similarly, chromosomes are capped by telomeres\u2014specialized complexes of repetitive DNA sequences and protective proteins that shield valuable genetic information at distal chromosomal tips from fraying or sticking to other chromosomes.<\/p>\n
Like aglets, telomeres are subject to degradation. Every time a cell divides, telomeres get a little shorter. Once they reach a critically short length, the cell reads this as DNA damage and permanently stops dividing. This irreversible growth-arrest state, called cellular senescence, is linked to chronic inflammation and contributes to age-related disease.<\/p>\n
For decades, scientists studying biomarkers of aging have investigated telomere length across species and individuals, as initial telomere length can vary even among members of the same species. The link between length and lifespan is complicated and confounded by many factors, but in mammals, starting life with shorter telomeres generally maps to higher risks of age-related disease and premature death.<\/p>\n
\u201cOn the flipside, if telomeres are too long, it can also spell trouble because cancer cells require long telomeres to become longer lived, \u2018immortal,\u2019\u201d says\u00a0Mia Levine<\/a>, associate professor of biology in the\u00a0School of Arts & Sciences<\/a>\u00a0at the\u00a0University of Pennsylvania<\/a>, who co-led research on the heritability of telomere lengths.<\/p>\n Levine and\u00a0Michael Lampson<\/a>, a professor of biology at Penn\u2019s School of Arts & Sciences, asked the extent to which telomere length inheritance follows the usual genetic rules. Specifically, is telomere length inherited as a polygenic trait, meaning it is influenced by many genes\u2014similar to eye color or height\u2014or are telomeres themselves inherited directly from egg and sperm cells?<\/p>\n \u201cWe wanted to ask how telomeres are really inherited,\u201d says Lampson. \u201cIs it just the telomere DNA sequence you inherit from your parents, or is it determined by the genes that regulate telomeres? What we found doesn\u2019t fit neatly into either box.\u201d<\/p>\n Published\u00a0in\u00a0Current Biology<\/a>, the team\u2019s experiments in an animal model support the existence of a parent-of-origin effect. When mothers contribute short telomeres and fathers contribute long ones, embryos elongate their telomeres. Reverse the pairing\u2014long from mom, short from dad\u2014and the embryos\u2019 telomeres shortened.<\/p>\n \u201cThis parent-of-origin effect is consistent with patterns we\u2019ve seen in human studies,\u201d Levine explains. \u201cFor example, children of older fathers tend to have longer telomeres than children of younger fathers. But teasing apart why that happens is difficult, because human studies are confounded by so many factors\u2014diet, smoking, stress, lifestyle. That\u2019s why we turned to a controlled animal model to test these ideas directly.\u201d<\/p>\n The researchers used mice with naturally long or short telomeres and performed reciprocal crosses\u2014swapping which parent contributed which telomere type. Because the offspring were genetically identical in both cases, any differences in telomere outcomes pointed to parent-of-origin effects rather than underlying DNA sequence. \u201cReciprocal crossing is what lets us detangle the usual confounders,\u201d Levine says.<\/p>\n Before the embryo switches on its own genome, it relies entirely on what\u2019s already in the egg and sperm. In a short window, between the first and second cell divisions, the team observed telomeres either elongating or shortening, a pivot that determined their length later in development.<\/p>\n The mechanism, the researchers report, looks less like the well-known enzyme telomerase, which adds DNA-protein complexes to chromosomal tips in germ and stem cells, and more like a pathway known as alternative lengthening of telomeres (ALT). This pathway, used by roughly 10\u201315% of cancers, \u201ccopies and pastes\u201d telomeric DNA from one chromosome to another rather than building it with telomerase.<\/p>\n The team\u2019s data support the idea that embryos can flip on a similar template-driven process and that it is sensitive to the asymmetry between maternal and paternal telomeres. Experimentally, only the first pairing consistently triggered ALT-like elongation. The reverse pairing produced the opposite effect, measurable shortening.<\/p>\n Looking ahead, the team are interested in seeing how these trends may or may not be mapping to humans.<\/p>\n \u201cOn the human side, we\u2019re now taking advantage of long-read genome sequencing,\u201d Levine says. \u201cThat lets us look directly at telomeres in family trios\u2014mom, dad, and child\u2014to ask if the same parent-of-origin effects we saw in mice are detectable in humans.\u201d<\/p>\n They are also interested in the implications for cancer research, as their embryonic model allows them to study the initiation of the ALT pathway.<\/p>\n \u201cWhen people study ALT in cancer cells, it\u2019s already been happening for many generations,\u201d Levine explains. \u201cBut in embryos, we can catch ALT at its very initiation, at the very first cell divisions. That gives us a window into how this pathway naturally gets switched on.\u201d<\/p>\n Reference: <\/b>Jeon HJ, Levine MT, Lampson MA. A parent-of-origin effect on embryonic telomere elongation determines telomere length inheritance. Current Biology. 2025;0(0). doi: 10.1016\/j.cub.2025.08.052<\/a><\/p>\n This article has been republished from the following materials<\/a>. Note: material may have been edited for length and content. For further information, please contact the cited source. 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