The Divergent Effects of Nicotinamide Riboside and High‐Intensity Exercise Training on Skeletal Muscle Epigenetic Aging
Year: 2026
Type: article
Abstract: ABSTRACT Aging is accompanied by a decline in physiological function and increased vulnerability to disease, with mitochondrial dysfunction and epigenetic alterations recognized as key hallmarks. Nicotinamide riboside (NR), a vitamin B3 precursor to NAD + , and high‐intensity interval training (HIIT) have both been proposed to ameliorate aging‐related mitochondrial decline, but their effects on skeletal muscle epigenetic aging are not fully elucidated. Here, we assessed the impact of 5‐month NR supplementation and 4–6 weeks HIIT on epigenetic age acceleration (EAA, via seven epigenetic clocks) in human skeletal muscle across three independent studies. NR supplementation was associated with reduced muscle EAA, particularly when measured with the PCHannum, MEAT, and DunedinPACE clocks, while HIIT produced opposite effects in some clocks, notably increasing pace of aging by DunedinPACE. Correlation analyses revealed that changes in skeletal muscle mitochondrial content correlated with changes in MEAT‐derived EAA after NR and 6 weeks of HIIT. Together, these findings indicate that skeletal muscle epigenetic aging can be modulated by NR and HIIT interventions but in opposing directions, highlighting a potential link between mitochondrial abundance and epigenetic clocks. Further studies are warranted to clarify how NR and exercise regulate epigenetic aging. These results offer new insights into development of strategies for promoting epigenetic outcomes and healthy aging.
Source: Aging Cell
DOI: 10.1111/acel.70638
Authors: Aino Heikkinen, Liina Uusitalo‐Kylmälä, Ida Blom, Jørn Wulff Helge, Linn Gillberg, Robert Seaborne, Steen Larsen, Macsue Jacques, Robin Grolaux, Sari Aaltonen, Jaakko Kaprio, Birgitta W. van der Kolk, Sini Heinonen, Nir Eynon, Kirsi H. Pietiläinen, Riikka Kivelä, Eija Pirinen, Miina Ollikainen
Institutions: University of Helsinki, Minerva Foundation, Institute for Molecular Medicine Finland, HiLIFE – Elämäntieteiden Instituutti, University of Jyväskylä, University of Copenhagen, Riga Stradiņš University, King's College London, Medical University of Białystok, Australian Regenerative Medicine Institute, Monash University, Helsinki University Hospital, Wihuri Research Institute, Oulu University Hospital, University of Oulu
Language: English
Subfield: Geriatrics and Gerontology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,790
Funders: Foundation for Cardiovascular Research, Helsingin Yliopisto, Suomen Lääketieteen Säätiö, Yrjö Jahnssonin Säätiö, Minerva Foundation, Academy of Finland, Suomen Kulttuurirahasto, Juho Vainion Säätiö, Novo Nordisk, Sydäntutkimussäätiö, Oulun Yliopisto, Paulon Säätiö, Paavo Nurmen Säätiö, Novo Nordisk Fonden, Diabetestutkimussäätiö
Awards: G1006267432, G1184637356, G1224646995, Novel targets to activate adipose tissue metabolism for the treatment of obesity, G1280640127, G1509028116, G1517598383, G1600861344, G1630871177, G1714132465, ADIPOSE AND MUSCLE TISSUE MITOCHONDRIAL PROFILING AS A KEY TO RENEWING THE TREATMENT OF OBESITY, G1820233071, G2068215330, G2144711835, G2211207374, G2228340177, G2257223166, G2305454263, G2384427189, G2475892237, G2583954406, G2811085312, G2874428645, G2996280776, Center of Excellence in Complex Disease Genetics-from Discovery to Precision Medicine, G3218009752, G3494606022, G3850253215, G3866446495, G3871240750, G3947144878, G4043554698, G406565379, G4065964368, G4148012336, G4180513299, G4344713917, G4411580604, G4415933063, G4575391396, G4741968299, G484840104, G4892916650, G4976537738, G5054526510, G5057296940, G5242406232, G5403377475, G551036691, G5585251843, G5622281932, Center of Excellence in Complex Disease Genetics-from Discovery to Precision Medicine, Individualized treatments for obesity based on mitochondrial biology, Individualized treatments for obesity based on mitochondrial biology, G623802957, G6266754447, G6406748394, G6635489528, G6644446059, G6760527719, G7325495115, Adipose tissue dysfunction as a driver of steatotic liver disease: Novel mechanisms and emerging therapeutic strategies, G7555853041, G7852328768, G7857482363, G7882649875, G8002632851, G8363947306, G837227766, G8374335932, G8419078628, G8749904515, G8793474095, G8830438197, G8875799215, G8880324339, G8891766075, G8907027324, G8966511090, G96990336, G980794150
OpenAlex ID: W7170035710