Person:
Sinha, Manisha

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Sinha

First Name

Manisha

Name

Sinha, Manisha

Filters

2013 - 20142

Settings

Author's Publications: search.filters.isAuthorOfPublication.331f503f-f659-4a3e-8366-7e7b6ae3f84e

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy
    (Elsevier BV, 2013) Loffredo, F; Steinhauser, Matthew; Jay, Steven M.; Gannon, Joseph; Pancoast, James R.; Yalamanchi, Pratyusha; Sinha, Manisha; Dall’Osso, Claudia; Khong, Danika; Shadrach, Jennifer; Miller, Christine; Singer, Britta S.; Stewart, Alex; Psychogios, Nikolaos; Gerszten, Robert; Hartigan, Adam J.; Kim, Mi-Jeong; Serwold, Thomas; Wagers, Amy; Lee, Richard
    The most common form of heart failure occurs with normal systolic function and often involves cardiac hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging, we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in which joining of animals of different ages leads to a shared circulation. After 4 weeks of exposure to the circulation of young mice, cardiac hypertrophy in old mice dramatically regressed, accompanied by reduced cardiomyocyte size and molecular remodeling. Reversal of age-related hypertrophy was not attributable to hemodynamic or behavioral effects of parabiosis, implicating a blood-borne factor. Using modified aptamer-based proteomics, we identified the TGF-b superfamily member GDF11 as a circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging.
  • Thumbnail Image
    Publication
    Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle
    (American Association for the Advancement of Science (AAAS), 2014) Sinha, Manisha; Jang, Y. C.; Oh, Juhyun; Khong, Danika; Wu, Elizabeth Y; Manohar, Rohan; Miller, Christine; Regalado, Samuel G.; Loffredo, F; Pancoast, James R.; Hirshman, Michael; Lebowitz, Jessica; Shadrach, Jennifer; Cerletti, Massimiliano; Kim, Mi Jeong; Serwold, Thomas; Goodyear, Laurie; Rosner, Bernard; Lee, Richard; Wagers, Amy
    Parabiosis experiments indicate that impaired regeneration in aged mice is reversible by exposure to a young circulation, suggesting that young blood contains humoral “rejuvenating” factors that can restore regenerative function. Here, we demonstrate that the circulating protein growth differentiation factor 11 (GDF11) is a rejuvenating factor for skeletal muscle. Supplementation of systemic GDF11 levels, which normally decline with age, by heterochronic parabiosis or systemic delivery of recombinant protein, reversed functional impairments and restored genomic integrity in aged muscle stem cells (satellite cells). Increased GDF11 levels in aged mice also improved muscle structural and functional features and increased strength and endurance exercise capacity. These data indicate that GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction.