Enhancing epigenetic aging clocks in cetaceans: accurate age estimations in small endangered delphinids, killer whales, pilot whales, belugas, humpbacks, and bowhead whales

Abstract This study presents refined epigenetic clocks for cetaceans, building on previous research that estimated ages in several species from bottlenose dolphins to bowhead and humpback whales using cytosine methylation levels. We combined publicly available data (generated on the HorvathMammalMet...

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Main Authors: Joseph A. Zoller, Ake T. Lu, Amin Haghani, Steve Horvath, Todd Robeck
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86705-5
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author Joseph A. Zoller
Ake T. Lu
Amin Haghani
Steve Horvath
Todd Robeck
author_facet Joseph A. Zoller
Ake T. Lu
Amin Haghani
Steve Horvath
Todd Robeck
author_sort Joseph A. Zoller
collection DOAJ
description Abstract This study presents refined epigenetic clocks for cetaceans, building on previous research that estimated ages in several species from bottlenose dolphins to bowhead and humpback whales using cytosine methylation levels. We combined publicly available data (generated on the HorvathMammalMethylChip40 platform) from skin (n = 805) and blood (n = 286) samples across 13 cetacean species, aged 0 to 139 years. By combining methylation data from different sources, we enhanced our sample size, thereby strengthening the statistical validity of our clocks. We used elastic net regression with leave one sample out (LOO) and leave one species out (LOSO) cross validation to produce highly accurate blood only (Median Absolute Error [MAE] = 1.64 years, r = 0.96), skin only (MAE = 2.32 years, r = 0.94) and blood and skin multi-tissue (MAE = 2.24 years, r = 0.94) clocks. In addition, the LOSO blood and skin (MAE = 5.6 years, repeated measures r = 0.83), skin only (MAE = 6.22 years, repeated measures r = 0.81), and blood only (MAE = 4.11 years, repeated measures r = 0.95) clock analysis demonstrated relatively high correlation toward cetacean species not included within this current data set and provide evidence for a broader application of this model. Our results introduce a multi-species, two-tissue clock for broader applicability across cetaceans, alongside single-tissue multi-species clocks for blood and skin, which allow for more detailed aging analysis depending on the availability of samples. In addition, we developed species-specific clocks for enhanced precision, resulting in four blood-specific clocks and eight skin-specific clocks for individual species; all improving upon existing accuracy estimates for previously published species-specific clocks. By pooling methylation data from various studies, we increased our sample size, significantly enhancing the statistical power for building accurate clocks. These new epigenetic age estimators for cetaceans provide more accurate tools for aiding in conservation efforts of endangered cetaceans.
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spelling doaj-art-c7f8d8efc8bd4fada84faa05ef1a30962025-02-09T12:28:12ZengNature PortfolioScientific Reports2045-23222025-02-0115111610.1038/s41598-025-86705-5Enhancing epigenetic aging clocks in cetaceans: accurate age estimations in small endangered delphinids, killer whales, pilot whales, belugas, humpbacks, and bowhead whalesJoseph A. Zoller0Ake T. Lu1Amin Haghani2Steve Horvath3Todd Robeck4Department of Biostatistics, Fielding School of Public Health, University of California, Los AngelesAltos LabsAltos LabsAltos LabsSeaWorld ParksAbstract This study presents refined epigenetic clocks for cetaceans, building on previous research that estimated ages in several species from bottlenose dolphins to bowhead and humpback whales using cytosine methylation levels. We combined publicly available data (generated on the HorvathMammalMethylChip40 platform) from skin (n = 805) and blood (n = 286) samples across 13 cetacean species, aged 0 to 139 years. By combining methylation data from different sources, we enhanced our sample size, thereby strengthening the statistical validity of our clocks. We used elastic net regression with leave one sample out (LOO) and leave one species out (LOSO) cross validation to produce highly accurate blood only (Median Absolute Error [MAE] = 1.64 years, r = 0.96), skin only (MAE = 2.32 years, r = 0.94) and blood and skin multi-tissue (MAE = 2.24 years, r = 0.94) clocks. In addition, the LOSO blood and skin (MAE = 5.6 years, repeated measures r = 0.83), skin only (MAE = 6.22 years, repeated measures r = 0.81), and blood only (MAE = 4.11 years, repeated measures r = 0.95) clock analysis demonstrated relatively high correlation toward cetacean species not included within this current data set and provide evidence for a broader application of this model. Our results introduce a multi-species, two-tissue clock for broader applicability across cetaceans, alongside single-tissue multi-species clocks for blood and skin, which allow for more detailed aging analysis depending on the availability of samples. In addition, we developed species-specific clocks for enhanced precision, resulting in four blood-specific clocks and eight skin-specific clocks for individual species; all improving upon existing accuracy estimates for previously published species-specific clocks. By pooling methylation data from various studies, we increased our sample size, significantly enhancing the statistical power for building accurate clocks. These new epigenetic age estimators for cetaceans provide more accurate tools for aiding in conservation efforts of endangered cetaceans.https://doi.org/10.1038/s41598-025-86705-5Epigenetic clockDNA methylationCetaceaBelugaCommon bottlenose dolphinHumpback whale
spellingShingle Joseph A. Zoller
Ake T. Lu
Amin Haghani
Steve Horvath
Todd Robeck
Enhancing epigenetic aging clocks in cetaceans: accurate age estimations in small endangered delphinids, killer whales, pilot whales, belugas, humpbacks, and bowhead whales
Scientific Reports
Epigenetic clock
DNA methylation
Cetacea
Beluga
Common bottlenose dolphin
Humpback whale
title Enhancing epigenetic aging clocks in cetaceans: accurate age estimations in small endangered delphinids, killer whales, pilot whales, belugas, humpbacks, and bowhead whales
title_full Enhancing epigenetic aging clocks in cetaceans: accurate age estimations in small endangered delphinids, killer whales, pilot whales, belugas, humpbacks, and bowhead whales
title_fullStr Enhancing epigenetic aging clocks in cetaceans: accurate age estimations in small endangered delphinids, killer whales, pilot whales, belugas, humpbacks, and bowhead whales
title_full_unstemmed Enhancing epigenetic aging clocks in cetaceans: accurate age estimations in small endangered delphinids, killer whales, pilot whales, belugas, humpbacks, and bowhead whales
title_short Enhancing epigenetic aging clocks in cetaceans: accurate age estimations in small endangered delphinids, killer whales, pilot whales, belugas, humpbacks, and bowhead whales
title_sort enhancing epigenetic aging clocks in cetaceans accurate age estimations in small endangered delphinids killer whales pilot whales belugas humpbacks and bowhead whales
topic Epigenetic clock
DNA methylation
Cetacea
Beluga
Common bottlenose dolphin
Humpback whale
url https://doi.org/10.1038/s41598-025-86705-5
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