Despite his youthful appearance, a lifetime of neglecting his health has left him profoundly out of shape.

out 在这里表示"脱离"的状态。 of 表示所属关系或状态。 shape 本义是"形状"，在这里指"身体状态"或"健康状况"。 out of shape 是一个固定短语，字面意思是"脱离良好状态"，实际指"身体状况不佳"或"身体走形"。