According to the United Nations World Population Prospects 2019, the human lifespan has increased substantially over the past half-century, and this trend is projected to continue well into the 21st Century. However, an extension of lifespan has not been accompanied by an equivalent healthspan; instead, the period of morbidity in old age has extended, and independence and quality of life have been attenuated.1
Lifelong exercisers show better physical function in old age than inactive individuals, suggesting that a certain level of exercise is required to optimise healthy ageing and healthspan.2 An important contributor for maintaining physical function is preserved muscle mass and function.3,4 Although the underlying mechanisms behind exercise-induced preservation of muscle mass and function are not yet fully understood, one possibility is the maintained ability to transduce forces to biochemical signals.
A group of proteins named the LINC complex—found within muscle fibres—are essential for the force transduction process and the regulation of gene expression.5,6 Thus, defects in the LINC complex and associated proteins can cause impaired muscle function, deformed nuclei, and misregulated gene expression, which negatively impact overall physical function and quality of life.
To investigate whether exercise can maintain the structure of the nuclei and the LINC complex organisation with age, members of Ochala and Stroud labs analysed muscle fibres from younger and older untrained individuals (24-36 years old and 68-90 years old, respectively), trained younger marathon runners (27 to 37 years old) and trained older endurance cyclists (73 to 79 years old). The results showed that the muscle fibre nuclei were strikingly more spherical in the endurance-trained individuals than the untrained counterparts, indicating differential DNA organisation in exercise among trained individuals and resulting in a gene
Figure 1: Nuclei are more circular in endurance trained individuals compared to untrained counterparts. Aspect ratio, a measure of nuclear circularity, was reduced in younger and older endurance trained individuals compared to untrained counterparts. Grey circles represent nuclei, coloured triangles represent individuals. P < 0.05 (Two-way ANOVA)
We also looked at the organisation of a LINC complex and an associated protein key for nuclear integrity and force transduction (SUN1 and Lamin A) and found no differences in the groups. This suggests other LINC complex proteins or scaffolding protein (Desmin) might play an important role in preserving mechanotransduction with age. Whether altered nuclear shape translates to changes in how nuclei respond to muscle cell stretching is an area of ongoing research.
In summary, more spherical nuclei are a common factor in participants—younger and older—with endurance training than untrained groups, which could contribute to the exercise-mediated maintenance of muscle mass and function throughout the lifespan. Analysis of nuclear mechanics and full characterisation of LINC complex proteins in these groups is an ongoing research focus.
Understanding better how the LINC complex works could highlight a target for a nutraceutical intervention to preserve muscle health throughout the lifespan.
- Younger untrained - Julien Ochala and Jorn Wulff Helge
- Younger marathon runners – Dr Jamie Pugh and Professor Graeme Close, Liverpool John Moores
- Master cyclists – Steve Harridge, Norman Lazarus, Ross Pollock, CHAPS
- Hip Fracture patients – Steve Harridge, Norman Lazarus, Ross Pollock, Michaeljohn Kalakoutis, CHAPS
- Medical Research Council, British Heart Foundation
- Brown, G.C., 2015. Living too long: the current focus of medical research on increasing the quantity, rather than the quality, of life is damaging our health and harming the economy. EMBO reports, 16(2), pp.137-141.
- Lazarus, N.R. and Harridge, S.D., 2017. Declining performance of master athletes: silhouettes of the trajectory of healthy human ageing? The Journal of Physiology, 595(9), pp.2941-2948.
- Wroblewski, A.P., Amati, F., Smiley, M.A., Goodpaster, B. and Wright, V., 2011. Chronic exercise preserves lean muscle mass in masters athletes. The Physician and Sportsmedicine, 39(3), pp.172-178.
- Mckendry, J., Breen, L., Shad, B.J. and Greig, C.A., 2018. Muscle morphology and performance in master athletes: A systematic review and meta-analyses. Ageing research reviews, 45, pp.62-82.
- Crisp, M., Liu, Q., Roux, K., Rattner, J.B., Shanahan, C., Burke, B., Stahl, P.D. and Hodzic, D., 2006. Coupling of the nucleus and cytoplasm: role of the LINC complex. The Journal of cell biology, 172(1), pp.41-53.
- Battey, E., Stroud, M.J. and Ochala, J., 2020. Using nuclear envelope mutations to explore age-related skeletal muscle weakness. Clinical Science, 134(16), pp.2177-2187.