The Study of Muscle Mobility and Aging (SOMMA) is a cohort uniquely designed to identify fundamental age-
related pathways contributing to important clinical and gerontologic outcomes. Newly elucidated biologic
pathways of aging have fueled an explosion of novel approaches hypothesized to extend health span.
However, how these pathways contribute to salient health outcomes in older adults such as disability and
dementia-free survival is not known. SOMMA2 extends SOMMA1, which tests the paradigm that properties of
muscle, including muscle mitochondrial energetics, predict the onset of objective mobility disability i.e., the
inability to walk 400m. Nevertheless, SOMMA1 established a rich repository of muscle tissue, blood, and
phenotyping, to expand research to other pathways and clinical endpoints. SOMMA2 builds on this foundation.
It integrates the talents of some of the nation’s leading aging researchers to understand the biological drivers
of age-related changes in physical function and the onset of disability and death. SOMMA2 will add 600 new
participants to increase its diversity and provide sufficient power to test whether biological pathways predict our
composite outcome of ADL disability, dementia, or death, and the co-primary outcome of objective mobility
disability. SOMMA2 will also gather unprecedented longitudinal data with repeat muscle biopsies to identify
changes in biological pathways in muscle tissue that are associated with age-related changes in muscle power
and cardiopulmonary fitness (VO2 peak). SOMMA2 will study distinct but interrelated biological pathways of
aging. DNA damage and insufficient repair lead to DNA mutations and clonal hematopoiesis. Increasing
oxidative stress damages lipids and proteins in muscle with aging, leading to declines in muscle power and
fitness. DNA damage and mitochondrial dysfunction may trigger cellular senescence in muscle and the pro-
inflammatory senescence associated secretory phenotype (SASP). SOMMA2 will also use longitudinal
transcriptomics in muscle to test hypotheses related to DNA damage/repair and senescence, and to discover
other pathways that influence change in power and fitness. SOMMA2 will employ repeated single nucleus
snRNA seq to reveal how changes in different muscle-resident cell types with aging contribute to the loss of
power and fitness. SOMMA has already become a major resource for investigators, particularly young
scientists, to study diverse facets of aging and provide career development opportunities. SOMMA will
continue to release data to the scientific community, provide data and specimens, and offer analytic help.
SOMMA2 will serve as a translational aging research engine for decades to come.